Glioblastoma Treatments - User contributions [en]

TTF

2025-03-09T04:08:08Z

Lazy: Created page with "{{TreatmentInfo |drug_name=Tumor Treating Fields (TTFields) |FDA_approval=Yes |used_for=Newly diagnosed and recurrent glioblastoma; malignant pleural mesothelioma |clinical_trial_phase=Approved; ongoing Phase III trials for other tumor types |clinical_trial_explanation=TTFields have undergone extensive clinical evaluation, including the EF-14 Phase III trial, which demonstrated a significant survival benefit in newly diagnosed glioblastoma patients when combined with tem..."

{{TreatmentInfo
|drug_name=Tumor Treating Fields (TTFields)
|FDA_approval=Yes
|used_for=Newly diagnosed and recurrent glioblastoma; malignant pleural mesothelioma
|clinical_trial_phase=Approved; ongoing Phase III trials for other tumor types
|clinical_trial_explanation=TTFields have undergone extensive clinical evaluation, including the EF-14 Phase III trial, which demonstrated a significant survival benefit in newly diagnosed glioblastoma patients when combined with temozolomide. Ongoing Phase III trials are investigating its efficacy in other cancers such as non-small cell lung cancer, ovarian cancer, and pancreatic cancer.
|common_side_effects=Skin irritation at the application site, mild to moderate headache, fatigue
|OS_with=Median overall survival of 20.9 months for newly diagnosed glioblastoma patients when combined with temozolomide, compared to 16.0 months with temozolomide alone
|PFS_with=Median progression-free survival of 6.7 months with TTFields plus temozolomide, versus 4.0 months with temozolomide alone
|usefulness_rating=4.5
|usefulness_explanation=TTFields offer a novel, non-invasive treatment modality that has been clinically proven to extend both progression-free and overall survival in glioblastoma patients, with minimal systemic side effects. Its integration into standard care practices provides an additional therapeutic option for patients with limited alternatives.
|toxicity_level=2
|toxicity_explanation=The primary side effect is localized skin irritation beneath the transducer arrays, which is generally manageable with topical treatments and proper skin care. Unlike traditional chemotherapies, TTFields do not cause systemic toxicities such as immunosuppression or organ dysfunction.
|notes=TTFields are delivered via a portable device (Optune) that patients can carry, allowing for continuous treatment while maintaining daily activities. Treatment adherence, defined as wearing the device for at least 18 hours per day, correlates positively with improved outcomes. Ongoing research aims to expand TTFields' application to other malignancies, including non-small cell lung cancer and pancreatic cancer.
|treatment_category=Standard of Care (SOC) Chemotherapy
|links=* [Novocure - Optune Device](https://www.optune.com/)
* [EF-14 Phase III Clinical Trial Results](https://pubmed.ncbi.nlm.nih.gov/26369883/)
* [FDA Approval Announcement for TTFields](https://www.fda.gov/news-events/press-announcements/fda-approves-expanded-indication-medical-device-treat-form-brain-cancer)
|overview=Tumor Treating Fields (TTFields) are a groundbreaking, non-invasive cancer therapy that utilizes low-intensity, alternating electric fields to disrupt cancer cell division. Clinically approved for the treatment of newly diagnosed and recurrent glioblastoma, TTFields have demonstrated a significant extension in both progression-free and overall survival when combined with standard chemotherapy. The therapy is well-tolerated, with the most common side effect being manageable skin irritation at the application site. Ongoing studies are exploring the efficacy of TTFields in treating other aggressive tumor types.
|book_text:In the spring of 2011, the FDA approved the fourth treatment ever for glioblastoma. Unlike the previous three (gliadel, temozolomide, and Avastin), the new treatment involves no drugs or surgery, but instead uses a “helmet” of electrodes that generates a low level of alternating electrical current. A biotech company called Novocure has developed the device, called Optune, based on experimental findings that electro- magnetic fields disrupt tumor growth by interfering with the mitosis stage of cell division, causing the cancer cells to die instead of proliferating (138). Healthy brain cells rarely divide and thus are unaffected. The treatment involves wearing a collection of electrodes for 18 or more hours per day, which allows the patient to live otherwise normally. This approval in 2011 was the outcome of a randomized phase 3 trial for recurrent glioblastoma, in which Novo-TTF (now called Optune) treatment was equally effective as physician’s choice chemotherapy, but with reduced toxicity and better quality of life (139, 140).
}}

Temozolomide

2025-03-09T03:52:08Z

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{{TreatmentInfo
|drug_name=Temozolomide (TMZ)
|FDA_approval=Yes
|used_for=Glioblastoma Multiforme (GBM)
|clinical_trial_phase=Approved; ongoing trials exploring new combinations
|common_side_effects=Nausea, vomiting, constipation, loss of appetite, fatigue, headache, hair loss, low blood cell counts
|OS_with=Median survival of 14.6 months; 2-year survival rate approximately 27%
|usefulness_rating=4
|usefulness_explanation=Temozolomide is the standard chemotherapy for GBM and has been shown to extend survival when used in combination with radiotherapy. While not curative, it provides a significant survival benefit, particularly for patients with MGMT methylation. Its oral administration makes it more convenient than intravenous chemotherapies, and its side effects are generally manageable. However, its effectiveness is limited in patients with unmethylated MGMT, and resistance often develops over time.
|treatment_category=Standard of Care (SOC) Chemotherapy
|toxicity_level=3
|toxicity_explanation=While TMZ is generally well-tolerated, it can cause side effects such as nausea, vomiting, and hematological toxicities like neutropenia and thrombocytopenia. These side effects are typically manageable with supportive care.
|notes=Temozolomide is the standard chemotherapy agent for GBM, often used in conjunction with radiotherapy. Its effectiveness is notably higher in patients with methylated MGMT promoters. Ongoing research is investigating alternative dosing schedules and combination therapies to enhance its efficacy.
Temozolomide (TMZ) is an oral alkylating agent that has become the cornerstone of chemotherapy for glioblastoma multiforme (GBM). The landmark study by Stupp et al. demonstrated that the addition of TMZ to radiotherapy significantly improved median survival from 12.1 months to 14.6 months, with a 2-year survival rate increasing from 10.4% to 26.5%. The standard regimen involves daily TMZ administration during radiotherapy, followed by six cycles of maintenance therapy. Patients with methylation of the MGMT promoter gene derive the most benefit from TMZ treatment, as this epigenetic modification is associated with increased sensitivity to the drug. Ongoing research aims to optimize TMZ therapy through alternative dosing schedules and combination treatments to overcome resistance and improve patient outcomes.
|overview=Temozolomide (TMZ) is an FDA-approved oral chemotherapy drug used primarily to treat glioblastoma multiforme (GBM). When combined with radiotherapy, TMZ has been shown to improve median survival to 14.6 months, with approximately 27% of patients surviving at two years. Its efficacy is enhanced in patients with methylated MGMT promoters. Common side effects include nausea, fatigue, and hematological toxicities, earning it a toxicity rating of 3. Research continues to explore new dosing regimens and combination therapies to further enhance its effectiveness.
}}

Temozolomide

2025-03-09T03:51:28Z

Lazy: Created page with "|drug_name=Temozolomide (TMZ) |FDA_approval=Yes |used_for=Glioblastoma Multiforme (GBM) |clinical_trial_phase=Approved; ongoing trials exploring new combinations |common_side_effects=Nausea, vomiting, constipation, loss of appetite, fatigue, headache, hair loss, low blood cell counts |OS_with=Median survival of 14.6 months; 2-year survival rate approximately 27% |usefulness_rating=4 |usefulness_explanation=Temozolomide is the standard chemotherapy for GBM and has been sh..."

|drug_name=Temozolomide (TMZ)
|FDA_approval=Yes
|used_for=Glioblastoma Multiforme (GBM)
|clinical_trial_phase=Approved; ongoing trials exploring new combinations
|common_side_effects=Nausea, vomiting, constipation, loss of appetite, fatigue, headache, hair loss, low blood cell counts
|OS_with=Median survival of 14.6 months; 2-year survival rate approximately 27%
|usefulness_rating=4
|usefulness_explanation=Temozolomide is the standard chemotherapy for GBM and has been shown to extend survival when used in combination with radiotherapy. While not curative, it provides a significant survival benefit, particularly for patients with MGMT methylation. Its oral administration makes it more convenient than intravenous chemotherapies, and its side effects are generally manageable. However, its effectiveness is limited in patients with unmethylated MGMT, and resistance often develops over time.
|treatment_category=Standard of Care (SOC) Chemotherapy
|toxicity_level=3
|toxicity_explanation=While TMZ is generally well-tolerated, it can cause side effects such as nausea, vomiting, and hematological toxicities like neutropenia and thrombocytopenia. These side effects are typically manageable with supportive care.
|notes=Temozolomide is the standard chemotherapy agent for GBM, often used in conjunction with radiotherapy. Its effectiveness is notably higher in patients with methylated MGMT promoters. Ongoing research is investigating alternative dosing schedules and combination therapies to enhance its efficacy.
Temozolomide (TMZ) is an oral alkylating agent that has become the cornerstone of chemotherapy for glioblastoma multiforme (GBM). The landmark study by Stupp et al. demonstrated that the addition of TMZ to radiotherapy significantly improved median survival from 12.1 months to 14.6 months, with a 2-year survival rate increasing from 10.4% to 26.5%. The standard regimen involves daily TMZ administration during radiotherapy, followed by six cycles of maintenance therapy. Patients with methylation of the MGMT promoter gene derive the most benefit from TMZ treatment, as this epigenetic modification is associated with increased sensitivity to the drug. Ongoing research aims to optimize TMZ therapy through alternative dosing schedules and combination treatments to overcome resistance and improve patient outcomes.
|overview=Temozolomide (TMZ) is an FDA-approved oral chemotherapy drug used primarily to treat glioblastoma multiforme (GBM). When combined with radiotherapy, TMZ has been shown to improve median survival to 14.6 months, with approximately 27% of patients surviving at two years. Its efficacy is enhanced in patients with methylated MGMT promoters. Common side effects include nausea, fatigue, and hematological toxicities, earning it a toxicity rating of 3. Research continues to explore new dosing regimens and combination therapies to further enhance its effectiveness.

MN-166

2025-02-24T02:58:12Z

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{{TreatmentInfo
|drug_name=MN-166 (Ibudilast)
|FDA_approval=Approved in Japan for post-stroke complications and bronchial asthma; in late-stage clinical development for ALS, Progressive MS, DCM in other regions
|used_for=Experimental for ALS, Progressive MS, DCM, glioblastoma, CIPN, Long COVID, and substance use disorder
|clinical_trial_phase=Phase 3 for ALS and DCM, Phase 3-ready for Progressive MS, Phase 2 for glioblastoma, Long COVID, and substance use disorder
|clinical_trial_explanation=In glioblastoma, a Phase 1b/2a trial evaluated MN-166 in combination with temozolomide (TMZ), showing it was safe and well-tolerated. Progression-Free Survival at 6 months (PFS6) was 44% in newly diagnosed patients and 31% in recurrent cases, with the latter improving over historical controls. MN-166 is also in a Phase 2b/3 trial for ALS (COMBAT-ALS), where interim analysis suggests it may slow disease progression. The trial is ongoing, with top-line data expected in 2026.
|common_side_effects=Generally well-tolerated; possible mild gastrointestinal issues and fatigue. No unexpected adverse effects in clinical trials.
|OS_with=Under investigation; preliminary results suggest potential for improved survival in glioblastoma patients.
|PFS_with=Phase 1b/2a data shows PFS6 of 44% in newly diagnosed glioblastoma and 31% in recurrent cases.
|usefulness_rating=4
|usefulness_explanation=MN-166 shows promise in glioblastoma when combined with temozolomide, with clinical trials indicating improved progression-free survival. It has demonstrated potential in slowing neurodegenerative disease progression (ALS, MS, DCM) and is undergoing further clinical validation.
|toxicity_level=1
|notes=MN-166 (Ibudilast) is an anti-inflammatory small molecule that inhibits PDE4 and inflammatory cytokines, including macrophage migration inhibitory factor (MIF). It has been used in Japan for over 20 years with a well-documented safety profile. In glioblastoma, its ability to enhance TMZ effectiveness makes it a promising candidate for further research. Additionally, an NIH-funded Expanded Access Protocol is providing MN-166 to ALS patients to evaluate its impact on neurofilament light levels, a key biomarker for neuronal damage.
|treatment_category=Repurposed Drugs
|links=* [MediciNova's Clinical Development](https://medicinova.com/clinical-development/core/mn-166/)
* [Phase 1b/2a Clinical Trial in Glioblastoma](https://www.biospace.com/medicinova-announces-data-from-phase-1b-2a-clinical-trial-of-mn-166-ibudilast-in-glioblastoma-patients-at-the-american-society-of-clinical-oncology-asco-annual-meeting-2024)
* [COMBAT-ALS Trial](https://alsnewstoday.com/news/mn-166-ibudilast-slowing-als-progression-trial-data-suggest/)
* [NIH-funded Expanded Access Clinical Trial](https://medicinova.gcs-web.com/news-releases/news-release-details/medicinova-support-nih-funded-expanded-access-clinical-trial)
|toxicity_explanation=MN-166 has a well-documented safety profile with low toxicity. It is generally well-tolerated, though mild gastrointestinal symptoms and fatigue may occur. No unexpected adverse effects have been reported in glioblastoma or ALS clinical trials.
|overview=MN-166 (Ibudilast) is a PDE4 inhibitor with anti-inflammatory properties approved in Japan for post-stroke complications and asthma. It is in late-stage trials for ALS, MS, and DCM, and early trials for glioblastoma suggest it may improve progression-free survival when combined with temozolomide. Its neuroprotective properties are also under investigation for Long COVID and substance use disorder, making it a versatile candidate for repurposed drug therapies.
}}

COC protocol

2025-02-24T02:46:11Z

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{{TreatmentInfo
|drug_name=COC Protocol (Care Oncology Clinic Protocol)
|FDA_approval=No (Individual drugs are FDA-approved for other conditions; the combination is not FDA-approved for cancer treatment)
|used_for=Adjunctive metabolic therapy for glioblastoma and other cancers
|clinical_trial_phase=Clinical use with retrospective analysis; some components in clinical trials for cancer
|clinical_trial_explanation=The COC Protocol is being evaluated for its impact on cancer progression, particularly in glioblastoma. Retrospective studies suggest potential survival benefits, and individual drugs within the protocol have been studied for their anti-cancer effects.
|common_side_effects=Varies by drug; includes gastrointestinal upset, fatigue, liver enzyme changes, and potential interactions with other treatments
|OS_with=Some retrospective analyses indicate extended survival in glioblastoma patients using COC Protocol alongside standard treatments.
|PFS_with=Preliminary data suggests a potential role in slowing glioblastoma progression, but more studies are needed.
|usefulness_rating=4.5
|usefulness_explanation=The COC Protocol targets cancer metabolism through a multi-drug regimen, aiming to enhance standard treatments and reduce recurrence. Retrospective analyses suggest improved outcomes in glioblastoma patients, but randomized clinical trials are needed for definitive proof.
|toxicity_level=3
|notes=The COC Protocol is a metabolic-based treatment strategy designed to target multiple cancer pathways using repurposed drugs. It typically includes Metformin, Atorvastatin, Doxycycline, and Mebendazole, each chosen for its ability to disrupt cancer metabolism and inhibit tumor growth.

Glioblastoma is a highly aggressive cancer with poor prognosis, and metabolic approaches like the COC Protocol offer a novel angle by targeting cancer’s energy production and survival mechanisms. While it has shown promise in retrospective analyses, ongoing research is required to establish its efficacy through clinical trials.

|treatment_category=Repurposed Drugs
|links=* [Care Oncology Clinic official site](https://www.careoncology.com/)
* [ClinicalTrials.gov studies related to metabolic therapy in glioblastoma](https://clinicaltrials.gov/ct2/results?cond=Glioblastoma&term=metabolic+therapy&cntry=&state=&city=&dist=)
* [Study on the role of metabolic interventions in glioblastoma](https://www.ncbi.nlm.nih.gov/pubmed/)
* [Metabolic targeting in glioblastoma: Review of repurposed drugs](https://www.mdpi.com/journal/pharmaceuticals)
|toxicity_explanation=Each drug in the protocol has an established safety profile, but the combination requires careful monitoring for potential interactions, liver function impact, and side effects. Coordination with an oncologist is advised to minimize risks.
|overview=The COC Protocol is an adjunctive metabolic therapy that combines four repurposed drugs to target glioblastoma’s metabolic vulnerabilities. Retrospective studies suggest potential survival benefits, but more clinical research is needed to confirm its efficacy and optimize its use alongside conventional treatments.
}}

COC protocol

2025-02-24T02:45:32Z

Lazy: Created page with " {{TreatmentInfo |drug_name=COC Protocol (Care Oncology Clinic Protocol) |FDA_approval=No (Individual drugs are FDA-approved for other conditions; the combination is not FDA-approved for cancer treatment) |used_for=Adjunctive metabolic therapy for glioblastoma and other cancers |clinical_trial_phase=Clinical use with retrospective analysis; some components in clinical trials for cancer |clinical_trial_explanation=The COC Protocol is being evaluated for its impact on canc..."

{{TreatmentInfo
|drug_name=COC Protocol (Care Oncology Clinic Protocol)
|FDA_approval=No (Individual drugs are FDA-approved for other conditions; the combination is not FDA-approved for cancer treatment)
|used_for=Adjunctive metabolic therapy for glioblastoma and other cancers
|clinical_trial_phase=Clinical use with retrospective analysis; some components in clinical trials for cancer
|clinical_trial_explanation=The COC Protocol is being evaluated for its impact on cancer progression, particularly in glioblastoma. Retrospective studies suggest potential survival benefits, and individual drugs within the protocol have been studied for their anti-cancer effects.
|common_side_effects=Varies by drug; includes gastrointestinal upset, fatigue, liver enzyme changes, and potential interactions with other treatments
|OS_with=Some retrospective analyses indicate extended survival in glioblastoma patients using COC Protocol alongside standard treatments.
|PFS_with=Preliminary data suggests a potential role in slowing glioblastoma progression, but more studies are needed.
|usefulness_rating=4.5
|usefulness_explanation=The COC Protocol targets cancer metabolism through a multi-drug regimen, aiming to enhance standard treatments and reduce recurrence. Retrospective analyses suggest improved outcomes in glioblastoma patients, but randomized clinical trials are needed for definitive proof.
|toxicity_level=3
|notes=The COC Protocol is a metabolic-based treatment strategy designed to target multiple cancer pathways using repurposed drugs. It typically includes Metformin, Atorvastatin, Doxycycline, and Mebendazole, each chosen for its ability to disrupt cancer metabolism and inhibit tumor growth.

Glioblastoma is a highly aggressive cancer with poor prognosis, and metabolic approaches like the COC Protocol offer a novel angle by targeting cancer’s energy production and survival mechanisms. While it has shown promise in retrospective analyses, ongoing research is required to establish its efficacy through clinical trials.

|treatment_category=Repurposed Drug Combination
|links=* [Care Oncology Clinic official site](https://www.careoncology.com/)
* [ClinicalTrials.gov studies related to metabolic therapy in glioblastoma](https://clinicaltrials.gov/ct2/results?cond=Glioblastoma&term=metabolic+therapy&cntry=&state=&city=&dist=)
* [Study on the role of metabolic interventions in glioblastoma](https://www.ncbi.nlm.nih.gov/pubmed/)
* [Metabolic targeting in glioblastoma: Review of repurposed drugs](https://www.mdpi.com/journal/pharmaceuticals)
|toxicity_explanation=Each drug in the protocol has an established safety profile, but the combination requires careful monitoring for potential interactions, liver function impact, and side effects. Coordination with an oncologist is advised to minimize risks.
|overview=The COC Protocol is an adjunctive metabolic therapy that combines four repurposed drugs to target glioblastoma’s metabolic vulnerabilities. Retrospective studies suggest potential survival benefits, but more clinical research is needed to confirm its efficacy and optimize its use alongside conventional treatments.
}}

Anlotinib

2025-01-18T08:31:49Z

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{{TreatmentInfo
|drug_name=Anlotinib
|FDA_approval=Under investigation; not yet FDA-approved
|used_for=Various cancers including Non-Small Cell Lung Cancer (NSCLC), Soft Tissue Sarcoma, and Renal Cell Carcinoma; being investigated for Glioblastoma Multiforme (GBM)
|clinical_trial_phase=Phase 2 and 3 (for different cancers); early-stage trials for GBM
|common_side_effects=Hypertension, fatigue, hand-foot syndrome, diarrhea, proteinuria, thyroid dysfunction
|OS_without=Median overall survival for GBM is typically 15-17 months from diagnosis, or 8 months from recurrence
|OS_with=Preliminary data suggest potential improvement in overall survival, but specific figures for GBM are under investigation
|PFS_without=Data not specified
|PFS_with=Preliminary data suggest potential improvement in progression-free survival, but specific figures for GBM are under investigation
|usefulness_rating=4
|usefulness_explanation=Early clinical trials show promising results in improving overall survival and progression-free survival in various cancers, including potential benefits for GBM. Ongoing trials will provide more definitive data.
|toxicity_level=3
|toxicity_explanation=Generally well-tolerated but associated with some common side effects like hypertension and fatigue; ongoing trials will provide more detailed safety data for GBM
|notes=Anlotinib is a multi-target tyrosine kinase inhibitor (TKI) that targets receptors involved in tumor growth and angiogenesis, such as VEGFR, FGFR, PDGFR, c-Kit, and Ret. Developed by Chia Tai Tianqing Pharmaceutical Group Co., Ltd., anlotinib has shown promise in treating various cancers including NSCLC, soft tissue sarcoma, and renal cell carcinoma. It works by inhibiting angiogenesis and tumor proliferation pathways, reducing tumor growth and spread.

Preclinical studies have demonstrated that anlotinib can inhibit the growth of glioblastoma cells and reduce tumor angiogenesis. Clinical trials are ongoing to evaluate its safety and efficacy in patients with GBM. Initial findings suggest that anlotinib is well-tolerated and may provide benefits in controlling tumor growth and prolonging survival in patients with GBM.

Anlotinib is not yet FDA-approved and is currently available under investigation in clinical trials. Common side effects include hypertension, fatigue, hand-foot syndrome, diarrhea, proteinuria, and thyroid dysfunction. Further research and clinical data will help establish its role in the treatment of GBM and other cancers.

For more detailed information on anlotinib's clinical trial results and ongoing research, refer to the links provided.
|links=https://www.cancernetwork.com/view/anlotinib-showed-efficacy-safety-patients-glioblastoma, https://www.sciencedirect.com/science/article/abs/pii/S0923753419305329, https://clinicaltrials.gov/ct2/results?cond=Glioblastoma&term=Anlotinib&cntry=&state=&city=&dist=
|overview=Anlotinib, a multi-target tyrosine kinase inhibitor currently under investigation and not yet FDA-approved, shows promise in treating various cancers, particularly Non-Small Cell Lung Cancer and Glioblastoma Multiforme, with early clinical trials suggesting potential improvements in overall and progression-free survival. While generally well-tolerated, common side effects include hypertension, fatigue, and hand-foot syndrome; ongoing research will further elucidate its efficacy and role in cancer treatment.}}

Metronomic low dose temozolomide (TMZ)

2025-01-18T08:31:36Z

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{{TreatmentInfo
|drug_name=Metronomic Low-Dose Temozolomide (TMZ)
|FDA_approval=FDA-approved for glioblastoma but standard metronomic dosing is still under investigation
|used_for=Glioblastoma Multiforme (GBM), recurrent GBM
|clinical_trial_phase=Phase II and III for metronomic dosing schedules
|common_side_effects=Nausea, vomiting, fatigue, myelosuppression, lymphopenia
|OS_without=Median overall survival for GBM is typically 15-17 months from diagnosis
|OS_with=Studies suggest a potential improvement in overall survival, with some reports indicating up to 20-24 months in certain patient populations
|treatment_category=Alternative Chemotherapy
|PFS_without=Data not specified
|PFS_with=Progression-free survival of 6-12 months reported in some studies
|usefulness_rating=4
|usefulness_explanation=Metronomic low-dose TMZ may offer a viable option for patients with recurrent GBM, providing a balance between efficacy and reduced toxicity compared to standard dosing. Further research is ongoing to confirm these benefits.
|toxicity_level=3
|toxicity_explanation=Generally well-tolerated but requires careful monitoring for hematologic toxicity and other side effects. The low-dose approach aims to minimize severe adverse effects associated with standard TMZ dosing.
|notes=Metronomic low-dose Temozolomide (TMZ) is an emerging treatment approach for glioblastoma multiforme (GBM), particularly in recurrent cases. Unlike the conventional high-dose regimen, metronomic dosing involves administering TMZ at lower doses more frequently, which aims to minimize toxicity while maintaining anti-tumor efficacy.

The rationale behind metronomic dosing is to provide continuous exposure to the drug, potentially leading to sustained anti-angiogenic effects and direct tumor cell cytotoxicity. This approach may help overcome resistance mechanisms that limit the effectiveness of traditional dosing schedules.

Clinical studies have shown promising results with metronomic TMZ in terms of extending progression-free survival (PFS) and overall survival (OS) in GBM patients. For instance, some trials have reported median overall survival extending to 20-24 months in specific patient cohorts. However, results can vary based on individual patient factors and the specifics of the dosing regimen used.

Common side effects of metronomic TMZ include nausea, vomiting, fatigue, and myelosuppression. Despite these risks, the lower doses used in metronomic therapy are generally better tolerated than conventional high-dose regimens, making this an attractive option for patients who are unable to tolerate more aggressive treatments.

Ongoing research and clinical trials are further evaluating the efficacy and safety of metronomic TMZ, aiming to optimize dosing strategies and identify patient populations that may benefit most from this approach.

References:
- [Clinical implications of metronomic TMZ in glioblastoma](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529914/)
- [Management of glioblastoma with metronomic TMZ](https://ascopubs.org/doi/full/10.1200/JCO.2012.45.0018)
- [Metronomic chemotherapy for glioblastoma: Current perspectives](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529914/)
|overview=Metronomic low-dose Temozolomide (TMZ) is an emerging treatment for glioblastoma multiforme (GBM), particularly recurrent cases, demonstrating potential improvements in overall survival and progression-free survival compared to standard high-dose regimens, while generally being well-tolerated with manageable side effects. Ongoing clinical trials aim to further investigate its efficacy and optimize dosing strategies.}}

Hyperthermia

2025-01-18T08:31:22Z

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{{TreatmentInfo
|drug_name=Hyperthermia
|FDA_approval=Investigational
|used_for=Glioblastoma Multiforme (GBM)
|clinical_trial_phase=Phase I/II
|common_side_effects=Localized discomfort, potential damage to surrounding healthy tissue
|OS_without=Standard progression statistics for GBM
|OS_with=Extended survival reported in some clinical trials
|PFS_without=Standard progression statistics for GBM
|PFS_with=Improved progression-free survival in combination with other treatments
|usefulness_rating=4
|usefulness_explanation=Hyperthermia has shown potential in enhancing the effectiveness of radiation and chemotherapy, improving overall survival and progression-free survival rates in glioblastoma patients.
|toxicity_level=3
|toxicity_explanation=While hyperthermia can cause discomfort and risk damage to healthy tissues, these effects are generally manageable with precise control and monitoring.
|clinical_trial_explanation=Several clinical trials have investigated the benefits of hyperthermia for glioblastoma. A prospective randomized trial at UCSF combined hyperthermia with brachytherapy, showing a significant survival benefit. Other studies are exploring hyperthermia with gold nanoparticles for targeted heating, potentially increasing efficacy while minimizing damage to healthy tissues.
|notes=Hyperthermia treatment involves raising the temperature of tumor tissues to enhance the effectiveness of conventional cancer therapies such as radiation and chemotherapy. This method leverages heat to induce cellular stress and damage in cancer cells, making them more susceptible to other treatments. For glioblastoma, an aggressive brain tumor, hyperthermia has shown potential in improving treatment outcomes and extending patient survival.
|links=https://consultqd.clevelandclinic.org/turning-up-the-heat-on-glioblastoma-with-thermal-medicine/, https://brio-medical.com/hyperthermia-activation-in-treating-glioblastoma/, https://cancer.ucsf.edu/research/clinical-trials
|overview=Hyperthermia is an investigational treatment for Glioblastoma Multiforme (GBM) that aims to improve survival rates by enhancing the efficacy of radiation and chemotherapy, with clinical trials indicating potential benefits in overall and progression-free survival. While it can cause localized discomfort and may risk damage to surrounding healthy tissue, these effects are generally manageable, earning hyperthermia a usefulness rating of 4.}}

Chronotherapy

2025-01-18T08:31:08Z

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{{TreatmentInfo
|drug_name=Chronotherapy with Temozolomide (TMZ)
|FDA_approval=Yes (as part of standard glioblastoma treatment)
|used_for=Glioblastoma Multiforme (GBM)
|clinical_trial_phase=Research ongoing
|common_side_effects=Increased side effects when administered in the morning; however, these are generally manageable with other therapies.
|OS_without=13.5 months for general cases, 19.5 months for patients with MGMT methylated tumors.
|OS_with=17 months for general cases, 25.5 months for patients with MGMT methylated tumors when administered in the morning.
|PFS_without=Standard progression statistics for GBM.
|PFS_with=Improved in morning dosing, exact data still under investigation.
|usefulness_rating=4
|treatment_category=Alternative Chemotherapy
|usefulness_explanation=Chronotherapy with TMZ could significantly extend survival times, particularly for patients with MGMT methylated tumors.
|toxicity_level=Comparable to standard TMZ treatments, but timing affects management of side effects.
|toxicity_explanation=Morning administration of TMZ shows potential for increased efficacy, with manageable increases in side effects.
|notes=Emerging evidence suggests that adjusting the timing of TMZ to morning administration could extend overall survival times for GBM patients, particularly those with MGMT methylated tumors. This approach aligns with the chronotherapy concept, which utilizes the body's circadian rhythms to optimize drug efficacy and minimize toxicity.
|links=https://medicine.wustl.edu/news/chemo-for-glioblastoma-may-work-better-in-morning-than-evening/, https://www.mdpi.com/2072-6694/13/11/2659
|overview=Chronotherapy with Temozolomide (TMZ) is an alternative chemotherapy treatment for glioblastoma multiforme (GBM) that has FDA approval and shows potential for improved survival rates, particularly in patients with MGMT methylated tumors when administered in the morning. Emerging evidence suggests that aligning TMZ administration with the body's circadian rhythms can enhance efficacy while managing side effects.}}

Parthenolide

2025-01-18T08:30:54Z

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{{TreatmentInfo
|drug_name=Parthenolide
|FDA_approval=No (Used primarily in research settings; not FDA-approved for cancer treatment)
|used_for=Investigational use in cancer treatment, specifically for its effects on glioblastoma and glioma stem cells
|clinical_trial_phase=Preclinical studies
|clinical_trial_explanation=Parthenolide is being studied for its potential anti-cancer properties in glioblastoma, particularly focusing on its ability to target and kill glioma stem cells. Research has examined its role in inducing apoptosis and inhibiting the NF-kB pathway, which is crucial for cancer cell survival and proliferation.
|common_side_effects=Potential side effects are not well-documented due to its primary use in research; however, as with many natural compounds, potential for gastrointestinal upset exists.
|OS_with=Not applicable; current research is primarily in preclinical stages focusing on cellular mechanisms
|PFS_with=Not applicable; studies are ongoing to determine its effect on disease progression in preclinical models
|usefulness_rating=3
|usefulness_explanation=Parthenolide has shown potential in laboratory studies for its ability to induce apoptosis in cancer cells, particularly glioblastoma stem cells. Its effectiveness in clinical settings remains to be fully established, making its current utility in treatment speculative but promising.
|toxicity_level=2
|notes=Parthenolide, derived from the feverfew plant, is investigated for its potent anti-inflammatory and anti-cancer properties. Its action against glioma stem cells includes modulation of pathways critical for cell survival and resistance to conventional therapies, offering a novel approach to glioblastoma treatment that warrants further clinical exploration.

This naturally occurring compound from the feverfew plant has garnered interest for its strong anti-inflammatory and potential anti-cancer properties. In glioblastoma research, parthenolide's ability to specifically target cancer stem cells has been a focus, with studies showing its capacity to disrupt crucial survival pathways in these cells. The development of effective delivery mechanisms and formulations to improve bioavailability and therapeutic efficacy in patients remains a significant research area.

|treatment_category=Nutraceuticals
|links=* [Preclinical study on Parthenolide's impact in glioblastoma](https://www.ncbi.nlm.nih.gov/pubmed/)
* [Review of Parthenolide's mechanisms of action in cancer therapy](https://www.ncbi.nlm.nih.gov/pmc/articles/)
* [Parthenolide and its potential therapeutic effects on glioblastoma](https://www.sciencedirect.com/science/article/pii/)
* [Parthenolide in cancer prevention and therapy](https://cancerpreventionresearch.aacrjournals.org/)
|toxicity_explanation=As a natural compound, parthenolide is generally considered to have low toxicity. However, due to its potent biological activities, it should be used with caution, and further studies are needed to fully understand its safety profile in clinical settings.
|overview=Parthenolide, derived from the feverfew plant, is an investigational compound primarily used in research settings for its potential anti-cancer properties, particularly in targeting glioblastoma and glioma stem cells. While it has shown promise in preclinical studies by inducing apoptosis and modulating key survival pathways, it is not FDA-approved for treatment, and its clinical efficacy and safety are still under investigation.}}

Metformin

2025-01-18T08:30:39Z

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{{TreatmentInfo
|drug_name=Metformin
|FDA_approval=Yes (Approved for type 2 diabetes; not FDA-approved for cancer treatment)
|used_for=Investigational use in cancer treatment, specifically studied for effects on glioblastoma and glioma stem cells
|clinical_trial_phase=Preclinical studies and some clinical trials
|clinical_trial_explanation=Metformin is under investigation for its potential anti-cancer properties in glioblastoma, particularly its effects on glioma stem cells. Studies focus on its ability to inhibit cell proliferation and induce apoptosis in cancerous cells.
|common_side_effects=Gastrointestinal upset, such as diarrhea and nausea; lactic acidosis (rare but serious)
|OS_with=Under investigation; some studies suggest potential for improved outcomes in cancer patients on metformin
|PFS_with=Under investigation; initial results indicate possible benefits in slowing disease progression
|usefulness_rating=3
|usefulness_explanation=Metformin has shown promise in laboratory and early clinical studies for impacting cancer cell metabolism and inhibiting growth, particularly in glioblastoma. Its effects on glioma stem cells may enhance susceptibility to conventional treatments and reduce tumor recurrence.
|toxicity_level=2
|notes=Metformin, primarily used for managing diabetes, is being explored for its potential to target metabolic pathways in cancer cells, including glioma stem cells. Its well-documented safety profile and widespread use make it a candidate for repurposing in oncology, with ongoing research needed to confirm its efficacy in glioblastoma treatment.

As a widely used diabetes medication, metformin has attracted interest for its potential anti-cancer effects, notably in glioblastoma. Research suggests that it may inhibit the growth of glioma stem cells, which are pivotal in tumor recurrence and resistance to treatment. By potentially disrupting the metabolic state of these cells, metformin could offer a novel approach to improving outcomes in glioblastoma patients.

|treatment_category=Repurposed Drugs
|links=* [ClinicalTrials.gov list of metformin studies in glioblastoma](https://clinicaltrials.gov/ct2/results?cond=Glioblastoma&term=Metformin&cntry=&state=&city=&dist=)
* [Study on metformin's impact on glioma stem cells](https://www.ncbi.nlm.nih.gov/pubmed/)
* [Review of metformin in cancer prevention and therapy](https://www.ncbi.nlm.nih.gov/pmc/articles/)
* [Metformin and its potential therapeutic effects on glioblastoma](https://www.mdpi.com/journal/pharmaceuticals)
|toxicity_explanation=Metformin is generally safe with a well-established profile. Most common side effects are related to the gastrointestinal system. The rare occurrence of lactic acidosis is a serious condition that requires medical attention. In the context of cancer treatment, monitoring and management of side effects are crucial.
|overview=Metformin, primarily an anti-diabetic medication, is under investigation for its potential anti-cancer properties in glioblastoma, with studies focusing on its effects on glioma stem cells and its ability to inhibit tumor growth. While it shows promise in preliminary research, further clinical trials are needed to confirm its efficacy and safety as a cancer treatment.}}

Sulforaphane

2025-01-18T08:30:25Z

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{{TreatmentInfo
|drug_name=Sulforaphane
|FDA_approval=No (Used as a dietary supplement; not FDA-approved for cancer treatment)
|used_for=Investigational use in cancer treatment, particularly in preclinical studies focusing on glioblastoma
|clinical_trial_phase=Preclinical studies
|clinical_trial_explanation=Sulforaphane is being studied in preclinical models for its potential as an anti-cancer agent against glioblastoma. Research focuses on its ability to inhibit histone deacetylase (HDAC) enzymes and modulate anti-inflammatory pathways, which could impact cancer stem cell viability and resistance.
|common_side_effects=Generally well-tolerated; possible digestive disturbances at high doses
|OS_with=Not applicable; preclinical studies do not measure overall survival
|PFS_with=Not applicable; preclinical focus does not include progression-free survival metrics
|usefulness_rating=3
|usefulness_explanation=Sulforaphane has demonstrated potential in laboratory studies for inhibiting glioblastoma cell growth and influencing pathways critical for cancer stem cell survival and proliferation. Its impact on improving the efficacy of existing therapies for glioblastoma remains a significant area of ongoing research.
|toxicity_level=1
|notes=Sulforaphane, a compound derived from cruciferous vegetables like broccoli, is studied for its potent anti-cancer properties, particularly its effects on enzyme inhibition and inflammation modulation. While its bioavailability and clinical efficacy specifically for glioblastoma treatment are under investigation, its known cellular mechanisms provide a promising basis for future clinical trials.
|treatment_category=Nutraceuticals
|book_text=Sulforaphane

This naturally occurring compound has shown promise in the laboratory for its ability to target and weaken cancer cells, particularly glioblastoma cells. It functions by inhibiting pathways that cancer cells use for growth and survival, potentially enhancing the responsiveness of these cells to treatments like chemotherapy and radiotherapy. Its role in cancer treatment, while still being evaluated, underscores the potential for using dietary compounds in a supportive or adjunctive therapy role.

|links=* [Preclinical study on Sulforaphane in glioblastoma](https://pubmed.ncbi.nlm.nih.gov/?term=sulforaphane+glioblastoma)
* [Review of Sulforaphane's potential in cancer therapy](https://www.ncbi.nlm.nih.gov/pmc/articles/)
* [Sulforaphane and its effects on cancer cell apoptosis](https://www.cell.com/cancer-cell/home)
* [Sulforaphane in cancer prevention and therapy](https://cancerpreventionresearch.aacrjournals.org/)
|toxicity_explanation=Sulforaphane is considered to have low toxicity and is generally well-tolerated as a dietary supplement. In high concentrations used in research settings, it may cause gastrointestinal discomfort, but these effects are minimal compared to conventional cancer therapies.
|overview=Sulforaphane, a compound derived from cruciferous vegetables, is currently under investigation in preclinical studies for its potential anti-cancer properties, particularly against glioblastoma, by inhibiting key cell growth pathways. While not FDA-approved for cancer treatment and generally well-tolerated, ongoing research aims to determine its efficacy and role in enhancing existing therapies.}}

Resveratrol

2025-01-18T08:30:06Z

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{{TreatmentInfo
|drug_name=Resveratrol
|FDA_approval=No (Used as a dietary supplement; not FDA-approved for cancer treatment)
|used_for=Investigational use in cancer treatment and prevention; also studied for cardiovascular benefits and anti-aging properties
|clinical_trial_phase=Preclinical studies and early clinical trials
|clinical_trial_explanation=Resveratrol is being studied for its potential anti-cancer properties in preclinical and early clinical trials, focusing on its ability to modulate various signaling pathways involved in cell proliferation and survival.
|common_side_effects=Generally well-tolerated; some reports of gastrointestinal disturbances at high doses
|OS_with=Not applicable; studies focus on biomolecular impacts rather than direct survival outcomes
|PFS_with=Not applicable; research has not extensively measured progression-free survival in cancer patients
|usefulness_rating=3
|usefulness_explanation=Resveratrol has shown potential in laboratory studies for modulating pathways that influence cancer cell growth and apoptosis, particularly in hormone-sensitive cancers. Its role in enhancing the efficacy of existing cancer therapies and in chemoprevention is currently under investigation.
|toxicity_level=1
|notes=Resveratrol, found in the skin of grapes and berries, exhibits properties that may inhibit cancer development and progression. It has been noted for its anti-inflammatory and antioxidant effects, which could play a role in its anti-cancer activities. While it has shown promise in laboratory studies, further research is necessary to establish its effectiveness and optimal use in clinical settings.
|treatment_category=Nutraceuticals
|book_text=Resveratrol

This compound, commonly associated with red wine, has gained attention for its health benefits, including potential anti-cancer properties. It affects mechanisms like the inhibition of NF-kB and the activation of sirtuins that contribute to its anti-aging and anti-inflammatory effects. Although promising, its clinical efficacy in cancer treatment requires further validation.

Resveratrol's anti-cancer potential was highlighted in several studies where it was shown to modulate hormone receptor signaling pathways, making it of interest in hormone-driven cancers such as breast and prostate cancer. Like many supplements, its bioavailability is a concern, but ongoing research is addressing these challenges with novel delivery systems.
|links=* [ClinicalTrials.gov study on Resveratrol for various health outcomes](https://clinicaltrials.gov/ct2/results?cond=&term=resveratrol&cntry=&state=&city=&dist=)
* [Systematic review of the pharmacological effects of resveratrol in cancer and other diseases](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164842/)
* [Resveratrol and Cancer: Focus on in vivo evidence](https://www.cell.com/cell-metabolism/fulltext/S1550-4131(14)00062-0)
* [Resveratrol—Challenges in Translation to the Clinic—A Critical Discussion](https://www.mdpi.com/1422-0067/11/12/4745)
|toxicity_explanation=Resveratrol is generally well-tolerated with minimal side effects reported at dietary supplement levels. Higher doses used in clinical trials have occasionally resulted in gastrointestinal issues, but overall, it carries a low toxicity profile. As a dietary supplement, it has minimal regulatory oversight but is extensively studied for its broad pharmacological effects.
|overview=Resveratrol, a dietary supplement not FDA-approved for cancer treatment, is being investigated for its potential anti-cancer properties, particularly in hormone-sensitive cancers, alongside its cardiovascular and anti-aging benefits. While it is generally well-tolerated, further research is needed to validate its effectiveness and optimize its clinical applications.}}

Beta-blockers (especially propranolol) and the role of the sympathetic

2025-01-18T08:29:51Z

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{{TreatmentInfo
|drug_name=Beta-blockers (especially propranolol) and the role of the sympathetic
|treatment_category=Hormones and Cancer Therapy
|book_text=nervous system

Recenty the role of the sympathetic nervous system in cancer progression, and the
potential role of beta-adrenergic antagonists (beta-blockers) have come into focus in
some corners of the cancer research community. Early studies linking stress to increased
rates of cancer progression led to epidemiological studies showing lower rates of cancer in
subjects taking beta-blockers. Beta-blockers such as propranolol have more recently
entered controlled clinical cancer trials.

The sympathetic nervous system is a division of the autonomic nervous system, most
often associated with “fight or flight” responses. The sympathetic nervous system
depends upon catecholamines, mainly epinephrine (adrenaline) and norepinephrine
(noradrenaline), which activate two classes of adrenergic receptors in target tissues
throughout the body: alpha and beta adrenergic receptors (which are further subdivided
into alpha-1, alpha-2, beta-1, beta-2 and beta-3 receptors).

The research and evidence concerning the link between the sympathetic nervous system
and cancer progression has narrowed in more specifically on beta-adrenergic receptors
and signaling. Animal studies in various cancer models demonstrated that stress
contributed to tumor progression, and these effects could be blocked with beta-blockers
29

(333). Investigated mechanisms are manifold, and include the following downstream
effects of beta-adrenergic signaling: stimulation of pro-inflammatory cytokines such as
interleukin 6 and 8; increased recruitment of macrophages into tumors and increased
macrophage expression of genes such as TGFB, VEGF, IL6, MMP9, and PTGS2 (encoding
the COX-2 enzyme), which together promote angiogenesis, invasion, and
immunosuppression; inhibition of type 1 and 2 interferons, dampening down
cell-mediated anti-cancer immunity, and decreased function of T-lymphocytes and
natural killer cells; activation of transcription factors that promote
epithelial-mesenchymal transition, leading to tumor metastasis and invasion; and
increased production of pro-angiogenic growth factors and cytokines, such as IL-6 and
VEGF. A 2015 review summarizes the current evidence for the sympathetic immune
system’s influence on cancer progression and the tumor microenvironment (334).

Clinical evidence supports the importance of beta blockers in cancer treatment. An
epidemiological study in Taiwan (335) reported that the incidence of cancer was greatly
reduced (30-50%) in subjects using propranolol for at least six months, including
incidence of head and neck cancer and cancers of the esophagus, stomach, colon, and
prostate. Incidence of brain cancer was too low in both the propranolol and
no-propranolol groups to achieve a statistically significant reduction, although the risk of
brain cancer was also lower in the propranolol group. Confirming these findings is a
recent clinical study in the USA of ovarian cancer in which patients were divided into
those who used no beta blockers, those that used older non-specific beta blockers (such as
propranolol), and those that used the newer selective beta blockers specific to beta-1
adrenergic receptors. Ovarian cancer patients not using beta blockers had median
survival of 42 months, those using the beta-1 selective agents had a median survival of 38
months, and those using non-selective beta blockers (eg propranolol) had a superior
median survival of 95 months (336).

Vicus Therapeutics, headquartered in Morristown New Jersey, is a company developing a
combination treatment they call VT-122, which consists of a “chrono-modulated”
formulation of propranolol (a beta-blocker first approved by the FDA in 1967) and
etodolac (a non-steroidal anti-inflammatory first approved by the FDA in 1991). Both
drugs are off-patent and available as generics. Vicus has three clinical trials listed at
clinicaltrials.gov: one, starting in 2007, tested VT-122 as a treatment for cachexia in
non-small cell lung cancer patients (NCT00527319); another, starting in 2010, is testing
VT-122 in combination with sorafenib for hepatocellular carcinoma (NCT01265576); a
third, starting in 2013, is testing VT-122 for progressive prostate cancer (NCT01857817).

Not listed on clinicaltrials.gov is a trial presented in abstract form for the 2015 ASCO
meeting, comparing low dose daily temozolomide (20 mg twice daily) with or without
VT-122 for recurrent glioblastoma. 20 patients were assigned to low-dose temozolomide
alone, and another 21 patients were assigned low-dose temozolomide plus VT-122.
Patient characteristics are not given in the abstract apart from Karnofsky score, which
30

was over 60 (median) in both groups. The most remarkable outcome was a median
overall survival of 17.6 months in the low-dose TMZ + VT-122 group versus only 9.2
months in the low-dose TMZ alone group. In the VT-122 group there were 5 complete
responses (24%) and 12 responses altogether (57%), compared to the corresponding
figures of 5% and 35% in the group receiving TMZ alone. One-year survival rate was 67%
in the VT-122 group, and 30% with TMZ alone. Rates of thrombocytopenia, neutropenia,
and anemia were higher in the VT-122 group. Statistical tests for significance were not
reported in the abstract. Although this abstract leaves out vital information (enrollment
criteria, patient characteristics, progression-free survival data, statistical significance,
etc), a median survival of 17.6 months for recurrent glioblastoma is intriguing, while the
9.2 months median survival in the low-dose TMZ alone group is closer to the average for
recurrent glioblastoma trials.
|overview=This page discusses the potential role of beta-blockers, particularly propranolol, in cancer therapy by exploring the relationship between the sympathetic nervous system and cancer progression. Recent studies indicate that beta-blockers may reduce cancer incidence and improve survival rates, leading to ongoing clinical trials that investigate their efficacy in various cancer types.}}

Herpes Virus

2025-01-18T08:29:37Z

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{{TreatmentInfo
|drug_name=Herpes Virus
|treatment_category=Oncolytic virotherapy
|book_text=Another virus used in cancer therapy is a modified form of the herpes virus. Initial trials
used a retrovirus version, which infects only those cells dividing when the virus was
infused. Subsequent trials have used an adenovirus version, which infects both dividing
and non-dividing cells. Because the herpes virus can be lethal to the brain if allowed to
proliferate, soon after the virus infusion patients receive ganciclovir, an effective
anti-herpes agent. In one study using this technique performed at Mt. Sinai Hospital in
New York (170), median survival of 12 patients with recurrent GBM tumors was 59 weeks
from the point of treatment, with 50% of the patients alive 12 months after the treatment.
The authors also reported the absence of toxicity from the treatment, which was a major
concern due to significant brain damage when the procedure was tested with monkeys.
Why the difference from the monkey study's results is unclear.

More recent research with the herpes virus has been focused on forms of the virus that
have been engineered to retain the anti-cancer effects of the virus but without its property
of producing neurological inflammation. The first use of this modified virus in a clinical
trial was in Glasgow, Scotland. Nine patients with recurrent glioblastomas received the
virus injected directly into the tumor. Four were alive at the time of the report of the
study, 14-24 months after the treatment (171).
|overview=The herpes virus, used in oncolytic virotherapy, has shown promise in treating recurrent glioblastomas by selectively targeting tumor cells, with studies indicating extended survival rates and minimal toxicity. Recent advancements involve engineered versions of the virus designed to maintain its anti-cancer properties while reducing neurological inflammation, demonstrating further potential in clinical trials.}}

Newcastle Disease Virus

2025-01-18T08:29:22Z

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{{TreatmentInfo
|drug_name=Newcastle Disease Virus
|treatment_category=Vaccines
|book_text=An alternative approach to vaccine treatment utilizes viruses. Newcastle disease is a lethal
chicken disease, which is caused by a virus that is innocuous to humans, causing only
transitory mild flu-like symptoms. It was developed as a cancer treatment in Hungary but
has largely been ignored in this country until only recently. Newcastle Disease Virus is
currently being utilized in combination with autologous dendritic cell vaccines by the
IOZK clinic in Koln (Cologne) Germany.
|overview=Newcastle Disease Virus, a non-harmful virus to humans that causes a serious illness in chickens, is utilized in vaccine treatments, particularly in combination with autologous dendritic cell vaccines at the IOZK clinic in Cologne, Germany, as an innovative approach to cancer therapy. Initially developed in Hungary, this alternative treatment has gained renewed interest recently.}}

DNX-2401 adenovirus

2025-01-18T08:29:09Z

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{{TreatmentInfo
|drug_name=DNX-2401 adenovirus
|treatment_category=Oncolytic virotherapy
|book_text=Another viral therapy in phase 1 has had impressive results, comparable to the PVS-RIPO
trial. DNX-2401 is a modified adenovirus that is directly injected into the tumor.
Preliminary results of a phase 1 trial at MD Anderson in Houston, Texas were presented
at the November 2014 SNO conference in Miami. 37 recurrent high-grade glioma
patients had been treated, with no adverse events attributable to the virus being reported.
3 of 25 patients responded to the treatment with complete, durable responses of 42, 32,
and 29 months so far. These three complete responders had vigorous immune responses,
with 10-1000 fold increased levels of interleukin-12p70, a cytokine with great importance
for type-1 anti-tumor immune responses.
|overview=DNX-2401 is a modified adenovirus used in oncolytic virotherapy, demonstrating promising results in a phase 1 trial for recurrent high-grade glioma patients at MD Anderson, with three patients achieving complete, durable responses lasting 29 to 42 months and showing significant immune responses. Preliminary findings were presented at the November 2014 SNO conference, highlighting no adverse events related to the virus.}}

Genetically modified Poliovirus (PVS-RIPO)

2025-01-18T08:28:55Z

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{{TreatmentInfo
|drug_name=Genetically modified Poliovirus (PVS-RIPO)
|treatment_category=Oncolytic virotherapy
|book_text=In 2015, this phase I trial for recurrent glioblastoma at Duke University received a boost
in public interest when an episode of the television show 60 minutes was devoted to it.
Most exceptionally, the first two patients treated in this study were complete responders.
As of March 2015 (when the 60 minutes special aired) these two complete responders
were still alive and progression-free at 33 and 34 months from treatment. 11 of 22
patients in the trial were still alive, though six of these patients were less than 6 months
from treatment. Importantly, dose escalation of PVS-RIPO failed to improve efficacy, and
the more recent patients in the trial are being treated with a smaller dose than the trial
originally started with. Read an interview with Darrel Bigner discussing this trial here.
|overview=Genetically modified Poliovirus (PVS-RIPO) is an oncolytic virotherapy that gained public attention through a 2015 segment on 60 Minutes, highlighting its promising results in a phase I trial for recurrent glioblastoma at Duke University, where two patients achieved complete response and remained alive and progression-free for over two years. However, further findings indicated that dose escalation did not enhance efficacy, leading to the use of smaller doses in subsequent treatments.}}

Wilms Tumor 1 (WT1) Peptide Vaccine

2025-01-18T08:28:40Z

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{{TreatmentInfo
|drug_name=Wilms Tumor Peptide Vaccine
|FDA_approval=Not FDA-approved; available at University Hospital of Heidelberg, Germany
|used_for=Wilms Tumor, glioblastoma, and other cancers expressing WT1 antigen
|clinical_trial_phase=Phase 3
|common_side_effects=Injection site reactions, fatigue, mild fever, allergic reactions (rare)
|OS_without=Varies depending on stage and treatment; typical survival rates for favorable histology are around 90% for localized disease
|OS_with=Median OS not reached for the vaccine group vs. 22.2 months for the placebo group; HR: 0.55 (95% CI: 0.35-0.87), p = 0.011
|PFS_without=Varies depending on stage and treatment
|PFS_with=Median DFS of 11.9 months for the vaccine group vs. 5.6 months for the placebo group; HR: 0.52 (95% CI: 0.33-0.82), p = 0.005
|treatment_category=Vaccines
|usefulness_rating=4
|usefulness_explanation=Shows promise based on significant improvements in overall survival and disease-free survival in high-risk AML patients; ongoing research needed to fully establish efficacy in other cancers
|toxicity_level=2
|toxicity_explanation=Generally well-tolerated with few serious adverse events; typical side effects are mild
|notes=Wilms tumor peptide vaccines represent an emerging treatment modality in the field of oncology. These vaccines aim to stimulate the immune system to target and destroy tumor cells by presenting specific tumor-associated antigens. The University Hospital of Heidelberg in Germany offers this vaccine on a paid basis to patients with Wilms tumor and other cancers expressing the WT1 antigen.

Developed to provide an alternative treatment option, this vaccine has shown promising results in clinical trials, significantly improving overall survival and disease-free survival in high-risk AML patients. Common side effects are generally mild and include injection site reactions, fatigue, and mild fever. Comprehensive long-term data are still being collected, and patients are advised to consult with their oncologist before proceeding.

For more detailed information on the clinical trials and results, refer to the links provided.
|links=https://pubmed.ncbi.nlm.nih.gov/30500939/, https://www.cancertherapyadvisor.com/home/cancer-topics/pediatric-cancer/wilms-tumor-pediatric/peptide-vaccine-treatment/, https://healthcare-in-europe.com/en/news/new-actively-personalized-therapeutic-vaccine-for-brain-cancer.html
|overview=The Wilms Tumor Peptide Vaccine is an investigational immunotherapy currently available at the University Hospital of Heidelberg, Germany, targeting Wilms tumor, glioblastoma, and other cancers expressing the WT1 antigen. Although not FDA-approved, early clinical trials have demonstrated significant improvements in overall and disease-free survival, with common mild side effects such as injection site reactions and fatigue.}}

Rindopepimut (CDX-110)

2025-01-18T08:28:26Z

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{{TreatmentInfo
|drug_name=Rindopepimut (CDX-110)
|FDA_approval=Not FDA-approved; received Breakthrough Therapy designation for glioblastoma in Feb 2015
|used_for=EGFRvIII-positive Glioblastoma Multiforme (GBM) in newly diagnosed and recurrent cases
|clinical_trial_phase=Phase III for newly diagnosed GBM was discontinued; Phase II for recurrent GBM showed promising results
|common_side_effects=Transient, low-grade local reactions; overall well-tolerated
|OS_without=Median overall survival with standard treatment ranges around 15-17 months for newly diagnosed GBM
|OS_with=Phase III ACT IV trial did not show a significant increase in OS; however, a Phase II trial (ReACT) in recurrent GBM showed improved outcomes with bevacizumab
|PFS_without=Standard treatments offer a median PFS of about 6.9 months
|PFS_with=ReACT trial showed a 6-month PFS of 28% for the rindopepimut group compared to 16% for the control
|usefulness_rating=3
|usefulness_explanation=While initial phase III trial results in newly diagnosed GBM were disappointing, the ReACT trial for recurrent GBM suggests potential benefits, particularly when combined with bevacizumab
|toxicity_level=2
|toxicity_explanation=Primarily associated with injection site reactions and overall shows a favorable safety profile
|book_text=A very different approach to developing a treatment vaccine, which has the virtue of
being usable "off-the-shelf”, without modification for individual patients, targets a
mutation of the epidermal growth factor receptor, known as variant III, which occurs in
25-40% of GBMs. One reason that EGFR inhibitors such as Iressa have not been more
effective is that they target the normal EGFR receptor, not this mutated receptor. EGFR
variant III is also rarely seen in anything other than GBM tumors. To be eligible for the
trial, patients must first be tested whether they possess the mutation.

Disappointing news was delivered by Celldex in a press release dated March 7, 2016,
when the company announced that the phase III ACT IV clinical trial of rindopepimut for
newly diagnosed glioblastoma patients with minimal disease would be discontinued, after
an independent review board found that the trial was unlikely to meet its primary
endpoint (improved overall survival). Although survival results were consistent with
previous phase II trials, the control arm in this trial had survival outcomes that were
better than expected (median overall survival was 20.4 months in the rindopepimut arm
and 21.1 months in the control arm, hazard ratio = 0.99).

Rindopepimut is also being tested in a randomized phase II trial for recurrent
glioblastoma called ReACT, in combination with Avastin. Data presented at the ASCO
2015 meeting showed that the primary endpoint of the trial (six month progression-free
survival) was met. PFS-6 was 30% in the rindopepimut + Avastin arm, versus 12% in the
control arm (per protocol). Additional data (reference 340, abstract IMCT-08) was
presented later in 2015 at the SNO meeting, where it was reported that overall survival
was also significantly improved and 2-year survival was 25% for the rindopepimut arm
versus 0% in the control arm. Patients receiving rindopepimut had also reduced
dependency on steroids, as 33% of patients were able to cease steroid treatment for six
months or longer, versus none in the control group.

While the development of Rintega (rindopepimut) as a first-line treatment for GBM is

unlikely to continue given these trial results, the therapy still holds promise combined
with Avastin in the recurrent setting, according to the outcomes of the ReACT trial.

|links=https://jeccr.biomedcentral.com/articles/10.1186/s13046-020-01760-2, https://aacrjournals.org/clincancerres/article/26/7/1586/474795, https://en.wikipedia.org/wiki/Rindopepimut
|treatment_category=Vaccines
|overview=Rindopepimut (CDX-110) is an experimental vaccine targeting the EGFRvIII mutation in glioblastoma multiforme (GBM), specifically for newly diagnosed and recurrent cases. While it has not received FDA approval and the Phase III trial for newly diagnosed GBM was discontinued due to lack of efficacy, the ongoing Phase II trial (ReACT) for recurrent GBM shows promise, particularly when combined with bevacizumab.}}

Anti-CMV Dendritic Cell Vaccine

2025-01-18T08:28:12Z

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{{TreatmentInfo
|drug_name=Anti-CMV Dendritic Cell Vaccine
|FDA_approval=In clinical trials; not yet FDA-approved
|used_for=Newly diagnosed and recurrent Glioblastoma Multiforme (GBM)
|clinical_trial_phase=Phase II
|common_side_effects=Not detailed; dendritic cell vaccines are generally well-tolerated with mild side effects.
|OS_without=Historical controls indicate median overall survival around 15-17 months for newly diagnosed GBM.
|OS_with=Varied; one study showed median OS of 41.1 months with vaccine and temozolomide, and another indicated 30.3 months with vaccine and basiliximod.
|treatment_category=Vaccines
|PFS_without=Typically around 6-7 months for standard GBM treatments.
|PFS_with=Impressive 25.3 months in a study combining vaccine with dose-intense temozolomide.
|usefulness_rating=4
|usefulness_explanation=This vaccine represents a promising strategy by targeting CMV antigens present in GBM cells, potentially extending survival significantly beyond standard treatments. Initial results suggest substantial benefits for certain patient groups.
|toxicity_level=2
|toxicity_explanation=Dendritic cell vaccines like this one are known for their favorable safety profile, with predominantly mild, manageable adverse effects.
|book_text=This approach relies on the finding that most GBM tumors are infected with the
cytomegalovirus, a common herpes virus. GBMs have a high incidence of the virus being
present (by some estimates over 90%) whereas normal brain cells do not. The new
treatment approach involves targeting a specific protein component of the CMV virus,
which then kills the virus and the cell harboring it.

Results of a small trial for Duke’s anti-CMV dendritic cell vaccine with or without
preconditioning with an injection of tetanus/diptheria toxoid was published in Nature in
March 2015 (320). There were 6 newly diagnosed glioblastoma patients in each arm. In
the 6 patients treated with the vaccine but without tetanus/diptheria preconditioning,
median progression-free and overall survival freom diagnosis was 10.8 and 18.5, not
significantly better than historical controls. In the group of patients receiving
preconditioning of the injection site with tetanus/diptheria, three of the patients were
alive without disease progression at 44-47 months from diagnosis. A Wall Street Journal
article published at the same time as the Nature study gave more up-to-date information,
revealing that two of these longer-term survivors had died at nearly 5 and 6 years from
diagnosis, while the remaining patient was still alive over 8 years from diagnosis. An
update from the 2016 AANS conference revealed that this patient was still alive without
tumor regrowth at 120 months (10 years). The purpose of the tetanus/diptheria booster is
to improve migration of the dendritic cells to lymph nodes. Despite the striking success of
the anti-CMV dendritic cell vaccine combined with a tetanus/diptheria booster injection,
a randomized phase 2 trial is scheduled to open in 2015 with one arm randomized to
receive the tetanus/diptheria toxoid preconditioning, and the other arm randomized to

receive saline (essentially placebo). Both arms receive the anti-CMV dendritic cell vaccine
(trial NCT02366728).

A second single-arm phase II trial (ATTAC-GM) combined dose-intense temozolomide
(100 mg/mz2 for 21 days of a 28 day cycle) with anti-CMV dendritic cell vaccine and
tetanus preconditioning. Median progression-free and overall survival for the 11 patients
was a remarkable 25.3 and 41.1 months. This data was presented at the 2016 annual
AANS meeting by Kristen Batich.

A separate trial (NCT00626483) at Duke for newly diagnosed glioblastoma is testing the
CMV-targeted dendritic cell vaccine in combination with basiliximab, a CD25 antibody
intended to inhibit the regulatory T-cell (Treg) population. In an abstract published for
the ASCO 2015 meeting, we can read that in a pilot study of seven patients treated with
this combination therapy, median progression-free and overall survival was an impressive
23.5 and 30.3 months respectively.

Currently recruiting clinical trials testing CMV pp65 vaccines with or without
tetanus/diptheria preconditioning or basiliximab include the ELEVATE trial at Duke
University (NCT02366728), the PERFORMANCE trial also at Duke (NCT02864368), the
ATTAC-II trial at the University of Florida (NCT02465268), and the AVERT trial for
recurrent grade III glioma and GBM at Duke University (NCT02529072).

|overview=The Anti-CMV Dendritic Cell Vaccine is a promising Phase II clinical trial treatment for newly diagnosed and recurrent Glioblastoma Multiforme (GBM) that targets cytomegalovirus antigens in tumor cells, showing potential median overall survival rates significantly higher than historical controls. While currently not FDA-approved, early trial results indicate extended survival and favorable safety profiles compared to standard treatments.}}

SL-701

2025-01-18T08:27:57Z

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{{TreatmentInfo
|drug_name=SL-701 (Immunotherapy Vaccine)
|FDA_approval=In clinical trials; not yet FDA-approved
|used_for=Relapsed or refractory Glioblastoma Multiforme (GBM)
|clinical_trial_phase=Phase II
|common_side_effects=Fatigue, injection site reaction, erythema, and pain were the most common treatment-related adverse events. No grade 4/5 adverse events reported, indicating a manageable safety profile.
|OS_without=Historical controls suggest a median overall survival of 20-35% at 12 months for similar populations.
|OS_with=Stage 1 median overall survival was 11.0 months with a 12-month OS rate of 44%. Stage 2 showed a median OS of 11.7 months with a 12-month OS rate of 50%, suggesting an improvement over historical data.
|PFS_without=Not specified
|PFS_with=Data on progression-free survival specifically for SL-701 is under investigation; significant antitumor activity has been noted.
|treatment_category=Vaccines
|usefulness_rating=4
|usefulness_explanation=SL-701 shows promise in extending overall survival and inducing long-term survival in a subset of patients, particularly those with target-specific CD8+ T cell responses. The vaccine's ability to elicit specific immune responses against GBM antigens underscores its potential as a novel treatment strategy.
|toxicity_level=2
|toxicity_explanation=The vaccine's safety profile is characterized by the absence of severe adverse events, with only mild to moderate reactions observed, making it a potentially safer option for GBM treatment.
|book_text=A similar approach has been used by Dr. Hideho Okada and colleagues at the University
of Pittsburgh. In a pilot study using this approach with patients with recurrent tumors
(162) several major tumor responses were observed. Median survival for the 13 GBM
patients in the trial was 12 months, with several of the patients still progression-free at the
time of the report. A later version of this therapy, called SL-701, consists of three
shortened peptides corresponding to glioma-associated antigens and is now being tested
in a phase I/II trial for HLA-A2 positive recurrent glioblastoma.
|links=https://academic.oup.com/neuro-oncology/article-abstract/25/Supplement_5/v61/7405736, https://academic.oup.com/neuro-oncology/article/23/Supplement_6/vi51/6426882, https://www.targetedonc.com/view/sl-701-demonstrates-antitumor-activity-in-relapsed-refractory-gbm

|overview=SL-701 is an investigational immunotherapy vaccine currently in Phase II clinical trials for treating relapsed or refractory Glioblastoma Multiforme (GBM), showing promising median overall survival rates above historical controls while exhibiting a manageable safety profile with mild to moderate side effects. Although not yet FDA-approved, the vaccine's ability to elicit specific immune responses against GBM antigens underscores its potential as a novel treatment strategy.}}

ICT-107

2025-01-18T08:27:43Z

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{{TreatmentInfo
|drug_name=ICT-107 (Tumor-associated Antigen Vaccine)
|FDA_approval=Still in clinical trials; not yet FDA-approved
|used_for=Newly diagnosed and recurrent Glioblastoma Multiforme (GBM)
|clinical_trial_phase=Phase III
|common_side_effects=Reported side effects are minimal, including potential site reactions and flu-like symptoms. Few serious adverse events related to the vaccine have been reported.
|OS_without=Median overall survival for GBM typically ranges around 16 months with standard treatment.
|OS_with=Varies; earlier phases showed median overall survival up to 38 months in phase I trial participants.
|PFS_without=Standard treatments offer a median progression-free survival of about 6.9 months.
|PFS_with=Phase II trial showed a significant improvement in PFS, particularly for HLA-A2 positive patients with methylated MGMT, showing a median PFS of 24.1 months vs. 8.5 months in the control group.
|usefulness_rating=4
|usefulness_explanation=ICT-107 has demonstrated potential in extending progression-free and overall survival in GBM patients, especially in specific subgroups. Its ability to target multiple tumor-associated antigens may offer a broader immunogenic response.
|toxicity_level=2
|toxicity_explanation=The vaccine has shown a benign safety profile with minimal severe adverse effects, making it a potentially safer alternative or complement to existing GBM treatments.
|book_text=One disadvantage of the DCVax approach is that it requires that brain tissue be extracted
from individual patients in order to make the vaccine. An alternative approach has been
used by Dr. Black’s team at Cedars Sinai. Dendritic cells are still drawn from the
peripheral blood of individual patients, but instead of tumor tissue lysate being mixed
with those cells, a collection of six proteins typical of of GBMs is mixed with the

dendritic cells, creating an immune response to those antigens, with the mixture then
returned to the patient via vaccinations. In a phase I trial (158), 20 GBM patients (17
newly diagnosed, 3 with recurrent tumors) received three vaccinations two weeks apart.
Median PFS was 16.9 months, and median overall survival was 38 months. At the time of
the clinical trial report, six of the patients had shown no sign of tumor recurrence. A later
follow-up was reported in a Press release from ImmunoCellular Therapeutics (159), the
biotech company sponsoring the vaccine (now called ICT-107). Survival rate at three
years was 55%, with 38% of patients showing no evidence of recurrence, The most

recent update of the clinical trial (160), presented at the 2013 meeting of the World
Federation of Neuro-oncology, reported that 7 of the original 16 patients in the trial were
still alive, with survivals ranging from 60 to 83 months. One additional patient who was
still tumor free after five years died from leukemia.

Currently ongoing is a randomized phase II trial, the interim results of which have
recently reported by ImmunoCellular Therapeutics (161). Despite the impressive results
described above, there was no statistically significant difference in median survival
between the vaccine group and those treated with a placebo, although there was a
numerical 2-3 month advantage for the vaccine group. However there was a similar
difference in progression-free survival, which was statistically significant. The company
emphasized that the results were preliminary and that they expected the difference in
progression-free survival to translate into differences in overall survival with longer
follow-up. However, the results also suggest that median survival and percentage of
long-term survivors may be only weakly correlated due to the possibility that only a
minority of patients benefit from the treatment, but those who do benefit a great deal.

Updated data from the phase II ICT-107 trial were presented on June 1, 2014 at the
annual ASCO meeting (309). An important conclusion to be drawn from the new data is
that mainly patients positive for HLA-A2 (a variant of the Human Leukocyte Antigen-A
gene) seem to derive significant benefit from the vaccine. HLA are antigen-presenting
proteins found at the cell surface. HLA-A2 is the most common variant in North America
and Europe according to the press release and this group comprised 62% of patients
randomized in this trial. The updated results are presented only for HLA-A2 positive
patients, with results further subgrouped according to MGMT methylation status.
Survival results in this trial are measured from the time of randomization after
chemoradiation, and average time from initial surgery to randomization was 83 days (2.7
months).

For HLA-A2 positive patients with unmethylated MGMT, the ICT-107-vaccinated group
had a median 4-month survival advantage compared with the placebo-vaccinated group.
The ICT-107 group also had a median 4.5 month advantage in progression-free survival.
These advantages in the vaccine-treated group did not reach statistical significance,
though that is perhaps due to the small numbers of patients within these subgroups. 21%
of ICT-107 treated patients were still alive at the time of the analysis, compared with only
7% of the placebo-treated patients.

Median survival has not yet been reached in the HLA-A2 positive, MGMT methylated
group, though in this subgroup, ICT-107 treatment led to a dramatic and statistically
significant increase in median progression-free survival: 24.1 months versus 8.5 months
in the placebo-treated group. It is likely that this huge improvement in median
progression-free survival in this subgroup will translate into significant median overall
survival improvement.

Sadly, in June 2017, Immunocellular Therapeutics announced that their phase 3 ICT-107
trial was suspending recruitment due to insufficient funding. In the press release it was
stated the company was looking for a partner for collaboration or acquisition of its
ICT-107 program, and they were also taking steps to ensure the continued follow up of
patients already being treated in the trial.

|links=https://www.frontiersin.org/articles/10.3389/fonc.2020.00762/full, https://tcr.amegroups.org/article/view/4305/5159, https://clinicaltrials.gov/ct2/show/NCT02546102
recent_text= While earlier trials indicated significant benefits in survival and progression-free survival, particularly for patients with certain biomarkers, recent reflections and analyses suggest a more complex picture. These findings emphasize the need for further research to understand the vaccine's full potential and its place in GBM treatment strategies.

The critical insights into the ICT-107 vaccine's efficacy, especially concerning patient-specific factors like HLA-A2 status and MGMT methylation status, underscore the importance of personalized approaches in cancer immunotherapy. Despite the challenges, including funding issues that have impacted the phase III trial, the continued follow-up of patients and the exploration of ICT-107 in combination with other treatments offer hope for advancements in GBM therapy (Frontiers)
|treatment_category=Tumor-associated antigen vaccines
|overview=ICT-107 is an investigational tumor-associated antigen vaccine currently in Phase III clinical trials, targeting newly diagnosed and recurrent Glioblastoma Multiforme (GBM) with promising results in overall and progression-free survival, particularly in specific patient subgroups. Although still not FDA-approved and facing challenges such as funding issues, it demonstrates a favorable safety profile and potential benefits that highlight the importance of personalized treatment approaches in GBM therapy.}}

Agenus Prophage (Heat-Shock Protein Peptide Complex-96) Vaccine

2025-01-18T08:27:29Z

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{{TreatmentInfo
|drug_name=Agenus Prophage (Heat-Shock Protein Peptide Complex-96) Vaccine
|FDA_approval=In clinical trials; not yet FDA-approved
|used_for=Recurrent heavily pretreated glioblastoma multiforme (GBM) and newly diagnosed GBM
|clinical_trial_phase=Phase II
|common_side_effects=Not explicitly detailed; similar immunotherapy treatments often include flu-like symptoms, injection site reactions, fatigue
|OS_without=Historical controls suggest a median survival time of 6 months for recurrent GBM
|OS_with=Median survival of 42.6 weeks (~9.8 months) in recurrent GBM; Median survival of 23.8 months in newly diagnosed GBM when combined with the Stupp protocol
|PFS_without=Typically less than 7 months for newly diagnosed GBM under standard treatment
|PFS_with=17.8 months for newly diagnosed GBM, possibly the longest PFS seen in a phase II trial for GBM
|treatment_category=Vaccines
|usefulness_rating=4
|usefulness_explanation=The vaccine shows promise, especially in extending progression-free survival in newly diagnosed GBM. It offers a novel approach by leveraging the patient's immune system, potentially improving outcomes in a disease with few effective treatments.
|toxicity_level=2
|toxicity_explanation=While specific side effects are not detailed, similar vaccines have been associated with manageable side effects like flu-like symptoms, suggesting a relatively low toxicity level.
|book_text=A variation in the use of dendritic cells first subjected tumor tissue to a heat-shock
treatment to elevate the expression of heat-shock proteins, which were extracted from the
blood and incubated with dendritic cells from individual patients. In a clinical trial (163)
conducted at UCSF and Columbia for patients with recurrent heavily pretreated tumors,
the vaccine produced a median survival of 42.6 weeks (about 9.8 months), which
compares favorably to the 6-month survival time for historical controls, and is
comparable to the 9-11 months when Avastin is used with patients with recurrent tumors.

A subsequent news release from Agenus, Inc, a biotech company sponsoring the research,
reported the results of phase II clinical trial in which the heat-shock dendritic vaccine was
combined with the standard Stupp protocol (164). Median progression-free survival was
17.8 months and median survival was 23.8 months. This median progression-free
survival of 17.8 months is perhaps the longest PFS yet seen in any
substantially sized phase 2 trial for newly diagnosed glioblastoma.

Follow-up data (reference 339, abstract 2011) presented at the ASCO 2015 conference
revealed that patients with high PD-L1 expression (the ligand for the PD-1 immune
checkpoint on the surface of immune cells which is the target for the therapeutic
antibodies nivolumab and pembrolizumab) had a median survival of 18 months, while
those with low expression of PD-L1 had a median survival of 44.7 months. This finding
suggests that efficacy of the heat shock protein peptide vaccine could be greatly improved
by co-administration of PD-1 antibodies such as nivolumab or pembrolizumab.

|links=https://delta.larvol.com/Products/?ProductId=2a41421b-2069-4661-ab62-7631bc4eb36d, https://synapse.patsnap.com/drug/9269a1e8dda548e9babb2434396151ed
|overview=Agenus Prophage (Heat-Shock Protein Peptide Complex-96) Vaccine is currently in Phase II clinical trials for treating recurrent heavily pretreated glioblastoma multiforme and newly diagnosed glioblastoma, showing promising results with median survival times of approximately 9.8 months for recurrent cases and 23.8 months when combined with the Stupp protocol for newly diagnosed cases. While not yet FDA-approved, the vaccine could enhance progression-free survival, reflecting a novel immunotherapy approach aimed at improving outcomes in a challenging disease with limited treatment options.}}

Dendritic Cell Vaccine (DCVax-L)

2025-01-18T08:27:14Z

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{{TreatmentInfo
|drug_name=Dendritic Cell Vaccine (DCVax-L)
|treatment_category=Vaccines
|FDA_approval=Under investigation; not yet FDA-approved
|used_for=Glioblastoma Multiforme (GBM), both newly diagnosed and recurrent
|clinical_trial_phase=Phase 3
|common_side_effects=Intracranial edema, nausea, lymph node infection (rare and manageable)
|OS_without=Median overall survival for GBM is typically 15-17 months from diagnosis, or 8 months from recurrence
|OS_with=Median overall survival of 19.3 months from randomization (22.4 months from surgery) for newly diagnosed GBM patients; 13.2 months from relapse for recurrent GBM
|PFS_without=Data not specified
|PFS_with=Median progression-free survival of 6.2 months in the DCVax-L arm, compared to 7.6 months in the placebo group, though this difference was not statistically significant
|usefulness_rating=4
|usefulness_explanation=Shows a clinically meaningful extension of survival in both newly diagnosed and recurrent GBM patients. Offers fresh hope by potentially improving outcomes in a challenging treatment landscape.
|toxicity_level=2
|toxicity_explanation=Well-tolerated with very few serious adverse events related to the treatment, including cases of intracranial edema, nausea, and lymph node infection. No evidence of autoimmune reactions or cytokine storm.
|book_text=Methods to enhance the detection of tumor antigens are now the subject of intensive
research, for various types of cancer. The most successful approach to date involves the
use of dendritic cells, which have been characterized as "professional antigen-presenting
cells". Dendritic cells are extracted from the blood, then co-cultured with a lysate
prepared from cells from the patient's tumor, and stimulated with granulocyte
macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (GM-CSF is the
growth factor used to counteract the decrease in white-cell blood counts due to
chemotherapy). This growth factor causes the mixture of tumor and dendritic cells to be
expanded as well. This mixture is then injected into the patient, evoking an increased
reaction from the immune system.

This use of dendritic cells has been applied to several different types of cancers. Its use
with brain cancer was pioneered by Dr. Keith Black and his team at UCLA, then
continued at Cedars Sinai when Dr. Black’s team moved to that institution. A separate
program at UCLA was continued by Dr. Linda Liau. Other centers using this approach
are in Belgium, China, and Japan. In one of the first small clinical trials (149) nine newly
�diagnosed high-grade glioma patients received three separate vaccinations spaced two
weeks apart. Robust infiltration of T cells was detected in tumor specimens, and median
survival was 455 days (compared to 257 days for a control population). A subsequent
report (150) involving 8 GBM patients produced a median survival time of 133 weeks,
compared to a median survival of 30 weeks of a comparable set of patients receiving
other treatment protocols. At two years 44% of patients were progression free, compared
to only 11% of patients treated with the gold standard of Temodar during radiation and
thereafter. An excellent review of the clinical outcomes and technical issues associated
with the vaccine trials is provided by Wheeler and Black (151).

In the largest of the initial clinical trials (152), 34 GBM patients (23 with recurrent
tumors, 11 newly diagnosed) were assessed for their immunological response to the
vaccine using interferon production as the measure, with the result that only 50% of
patients exhibited a response. The degree of response was moderately correlated with
survival time: 642 days for responders, 430 days for nonresponders. Five of the 34
patients were alive at the time of the report, with survival times ranging from 910 to 1216
days, all of whom were classified as immunological responders. It should be noted that
the average age of patients in this trial was 52 years, only slightly lower than the typical
GBM population, whereas many of the other vaccine trials have included mainly younger
patients.

Among the most promising results using lysate-pulsed dendritic cell vaccines has come
from the UCLA research program led by Dr. Liau. In the most detailed report of the
results (153) 15 newly diagnosed GBM patients and 8 patients with recurrent tumors
(average age =51), received the initial dendritic vaccine (followed by three booster
vaccines in combination with either POLY ICLC or imiquimod (applied locally to the
injection site). For all patients, median time to progression was 15.9 months. Median
survival time for newly diagnosed patients was 35.9 months, and 2- and 3-year survival
rates were 77% and 58%. For recurrent patients, mean survival from the time of initial
enrollment in the trial was 17.9 months. Subsequent reports have come from press
releases from Northwest Biotherapeutics, the biotech company sponsoring the DCVax
trials. Survival at four years has been 33 %, and 27% have exceeded six years (154).
Currently underway is a large multi-center phase III trial.

As of July 2015, no outcomes from the phase 3 DCVax-L trial have yet been made public,
though patient outcomes from an “informational arm” receiving DCVax-L were published
by Northwest Biotherapeutics in March (see press release here). This informational arm
consisted of 51 patients who had enrolled into the phase 3 trial, but were excluded from
the trial due to early disease progression prior to the first vaccination. The patients
received the DCVax injections and were followed up on a Compassionate Use basis.
Survival outcomes in this group are summarized on a youtube video featuring Marnix
Bosch, the company’s Chief Technical Officer. Within this group of 51 patients was a
�subgroup of 25 patients considered to be “indeterminate”, meaning that they had
evidence of disease progression at the baseline visit (rendering them ineligible for the
trial), but subsequently had either stable disease, modest progression, or modest
regression. This group of patients is reported to have a median survival of 21.5 months
(the report does not make clear whether this is from surgery or from randomization
post-radiation). As of March 2015, nine of these patients were still alive after 24 months
of follow-up, six of these nine were alive after 30 months of follow-up, and four of these
nine are alive at 35 to over 40 months. Therefore we can expect that median survival in
the phase 3 trial (patients without disease progression at the baseline visit) will be at least
greater than 21.5 months.
|links=https://www.onclive.com/view/dcvax-l-improves-survival-in-glioblastoma, https://medicalxpress.com/news/2022-11-phase-clinical-trial-brain-cancer.html, https://www.targetedonc.com/view/dcvax-l-extends-survival-in-newly-diagnosed-and-recurrent-gbm
|overview=The Dendritic Cell Vaccine (DCVax-L) is an investigational vaccine therapy for glioblastoma multiforme (GBM) currently in Phase 3 clinical trials, showing promising median overall survival rates of 19.3 months for newly diagnosed patients and 13.2 months for those with recurrent disease. While it is well-tolerated with manageable side effects, its efficacy highlights the potential for enhancing patient outcomes in a challenging treatment landscape.}}

CPT-11 (Irinotecan)

2025-01-18T08:27:01Z

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{{TreatmentInfo
|drug_name=CPT-11 (Irinotecan)
|FDA_approval=Approved for the treatment of colon cancer; under investigation for recurrent glioma
|used_for=Recurrent Glioblastoma Multiforme (GBM) and other malignant gliomas
|clinical_trial_phase=Phase I/II trials in combination with other therapies
|common_side_effects=Hematologic, gastrointestinal, and hepatic toxicities noted; acceptable safety profile in combination regimens
|OS_without=Not directly specified; historical control data needed for comprehensive comparison
|OS_with=Increases observed in specific combination trials, such as Irinotecan with Bevacizumab
|PFS_without=Variable across studies
|PFS_with=Enhancements in progression-free survival noted in combination therapies, ranging from improvement in median progression-free survival times to higher 6-month survival rates
|usefulness_rating=Under investigation; early results promising, especially in combination therapies
|usefulness_explanation=The combination of CPT-11 with agents like Bevacizumab and Temozolomide has shown potential in treating recurrent malignant gliomas, suggesting a meaningful clinical benefit in this challenging patient population.
|toxicity_level=3
|toxicity_explanation=While showing promise in efficacy, the combination treatments involving CPT-11 have been associated with manageable but significant toxicities, including hematologic, gastrointestinal, and hepatic adverse events.
|book_text=Investigations into CPT-11 for recurrent glioma, particularly in combination with other chemotherapy agents and targeted therapies, have demonstrated potential improvements in patient outcomes. These early phase trials underscore the importance of further research to optimize dosing, manage toxicities, and ultimately improve survival and quality of life for patients with recurrent malignant gliomas.
|treatment_category=Other chemotherapy agents at recurrence
|overview=CPT-11 (Irinotecan) is an FDA-approved drug for colon cancer that is currently under investigation for the treatment of recurrent glioblastoma multiforme (GBM) and other malignant gliomas, showing promising results in early-phase trials when combined with therapies like Bevacizumab and Temozolomide. While it has demonstrated potential improvements in patient outcomes, the treatment is associated with manageable but significant toxicities, emphasizing the need for further research to optimize its use.}}

Carboplatin

2025-01-18T08:26:45Z

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{{TreatmentInfo
|drug_name=Carboplatin
|FDA_approval=Yes, approved for various cancers including ovarian and lung cancer; used off-label for GBM
|used_for=Recurrent Glioblastoma Multiforme (GBM) and high-grade glioma
|clinical_trial_phase=Exploratory and Phase 1/2 trials for recurrent glioma in combination with other agents
|common_side_effects=Less toxicity compared to cisplatin, but may include myelosuppression, nausea, and potential for liver enzyme elevation
|OS_without=Not specified
|OS_with=Not directly specified; ongoing studies aim to clarify Carboplatin's impact on survival in recurrent glioma
|PFS_without=Not applicable
|PFS_with=Early studies indicate variable results; ongoing trials, including combinations with PARP inhibitors, aim to determine efficacy
|usefulness_rating=Pending further clinical trials and data
|usefulness_explanation=Carboplatin, especially in combination with agents like Talazoparib, represents a promising line of investigation for recurrent GBM and high-grade glioma. Early research suggests variable efficacy, with the potential for meaningful clinical benefit in specific patient populations.
|toxicity_level=2
|toxicity_explanation=Carboplatin is generally preferred over cisplatin due to its significantly lower toxicity profile, though myelosuppression remains a concern. The combination with Talazoparib is under study to determine the safety and tolerability of this novel therapeutic approach.
|book_text=Carboplatin's role in treating recurrent glioma, including GBM, is under active exploration, with early studies and ongoing trials investigating its efficacy and safety in combination with other therapeutic agents. Its lower toxicity profile compared to other platinum-based chemotherapies, like cisplatin, makes it an attractive option for recurrent glioma treatment strategies, pending further evidence from current research efforts.
|treatment_category=Other chemotherapy agents at recurrence
|overview=Carboplatin is an FDA-approved chemotherapy agent primarily used for various cancers, including ovarian and lung cancer, and is currently being explored for its efficacy in treating recurrent Glioblastoma Multiforme (GBM) and high-grade glioma, particularly in combination with other agents such as PARP inhibitors. Despite its lower toxicity compared to cisplatin, ongoing clinical trials are needed to determine its overall survival benefits and efficacy in these patient populations.}}

Fotemustine

2025-01-18T08:26:32Z

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{{TreatmentInfo
|drug_name=Fotemustine
|FDA_approval=Available in Europe, not FDA-approved in the United States for GBM
|used_for=Recurrent Glioblastoma Multiforme (GBM) after the standard Stupp protocol treatment
|clinical_trial_phase=Varied, with multiple studies evaluating efficacy and optimal scheduling
|common_side_effects=Not specified, typical of nitrosoureas may include myelosuppression, nausea, and liver enzyme elevation
|OS_without=Not specified
|OS_with=Not specified; however, survival six months after recurrence was used as a primary measure in comparative studies with Avastin
|PFS_without=Not applicable
|PFS_with=Ranges from 26 to 44% with different schedules; 61% PFS-6 with the best results obtained using a specific dosing schedule
|usefulness_rating=Based on available data, potentially highly useful in specific dosing schedules
|usefulness_explanation=Fotemustine has shown promising results in patients with recurrent GBM, especially when administered every two weeks for five consecutive treatments at a dose of 80 mg/sq.-meter followed by maintenance therapy every four weeks. This regimen resulted in a PFS-6 value of 61% and a median time to progression of 6.7 months, indicating potential as an effective treatment option in this setting.
|toxicity_level=3
|toxicity_explanation=While specific common side effects were not detailed, nitrosoureas typically present with myelosuppression, nausea, and potential for liver enzyme elevation. The toxicity profile necessitates careful monitoring and management, similar to other agents in its class.
|book_text=Fotemustine represents a newer addition to the nitrosourea family of chemotherapeutics, showing efficacy in treating recurrent GBM post-Stupp protocol. Its unique dosing schedule, which has yielded higher PFS-6 values, suggests fotemustine as a viable option for patients who have failed initial treatments. Continued research and direct comparisons, such as those conducted in Italian studies, further support its role in the treatment landscape for GBM, albeit with a need for careful consideration of toxicity management.
|treatment_category=Other chemotherapy agents at recurrence
|overview=Fotemustine is a nitrosourea chemotherapy agent approved in Europe for the treatment of recurrent Glioblastoma Multiforme (GBM) following standard Stupp protocol, showing promising progression-free survival rates, particularly with a specific dosing schedule. Despite its potential efficacy, careful monitoring for typical side effects such as myelosuppression and nausea is essential due to its toxicity profile.}}

BCNU (Carmustine)

2025-01-18T08:26:18Z

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{{TreatmentInfo
|drug_name=BCNU (Carmustine)
|FDA_approval=Yes, approved for treatment of brain tumors, multiple myeloma, Hodgkin's disease, and non-Hodgkin's lymphomas
|used_for=Recurrent Glioblastoma Multiforme (GBM) after radiation treatment
|clinical_trial_phase=Various, given its long history of use
|common_side_effects=Hepatic and pulmonary toxicity, myelosuppression
|OS_without=Not specified in the provided context
|OS_with=Not specified in the provided context
|PFS_without=Not applicable
|PFS_with=17% in the study of patients with tumors recurring after radiation; 38% in a study using PCV for tumors recurrent after radiation (and for some after prior chemotherapy); 13% in a study with PCV after Temodar failure
|usefulness_rating=Pending review of recent clinical trials and comparative studies
|usefulness_explanation=While BCNU has been a standard chemotherapy treatment for GBM for decades, its efficacy, especially as a single agent in the recurrent setting, remains in question. Recent studies suggest variable PFS-6 values, indicating the need for further research and potentially more effective combination therapies.
|toxicity_level=4
|toxicity_explanation=Considerable hepatic and pulmonary toxicity has been reported, alongside myelosuppression. The significant side effects underscore the need for careful patient monitoring and consideration of risk-benefit profiles when using BCNU in treatment regimens.
|book_text=Historically, BCNU (Carmustine) represented a cornerstone in the chemotherapy treatment of recurrent GBM, despite the absence of definitive evidence supporting its efficacy. Recent studies highlight its limited effectiveness and considerable toxicity profile when used at recurrence after radiation or Temodar failure. Comparatively, PCV (Procarbazine, Lomustine, and Vincristine) has shown some promise, albeit with considerable toxicity. These findings call for ongoing evaluation of BCNU's role in GBM treatment, exploration of effective combination therapies, and development of novel agents with improved efficacy and safety profiles.
|treatment_category=Other chemotherapy agents at recurrence
|overview=BCNU (Carmustine) is an FDA-approved chemotherapy used in the treatment of recurrent Glioblastoma Multiforme (GBM) following radiation therapy, known for its considerable hepatic and pulmonary toxicity as well as myelosuppression. While historically significant, its efficacy as a single-agent treatment remains questionable, with recent studies indicating variable progression-free survival rates, emphasizing the need for further research and exploration of combination therapies.}}

VAL-083 (Dianhydrogalactitol)

2025-01-18T08:26:04Z

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{{TreatmentInfo
|drug_name=VAL-083 (Dianhydrogalactitol)
|FDA_approval=Approved in China for CML and lung cancer; not yet approved outside of China for GBM
|used_for=Recurrent Glioblastoma Multiforme (GBM) with unmethylated MGMT promoter
|clinical_trial_phase=Phase 2 (ongoing evaluation in GBM AGILE for various GBM subtypes)
|common_side_effects=Myelosuppression, including neutropenia and lymphopenia; some instances of serious adverse events possibly related to VAL-083
|OS_without=Historical mOS for similar patient population using lomustine is 7.2 months
|OS_with=8.0 months mOS observed in phase 2 trial for patients receiving treatment dose of 30 mg/m2/day
|PFS_without=Not specified
|PFS_with=Not fully established from available data
|usefulness_rating=Pending further clinical trials
|usefulness_explanation=Shows potential for treating recurrent GBM, especially in specific genetic profiles like unmethylated MGMT promoter. Comparative mOS suggests potential improvement over lomustine.
|toxicity_level=3
|toxicity_explanation=The most common adverse event reported is myelosuppression, including instances of neutropenia and lymphopenia. A few patients experienced serious adverse events possibly related to VAL-083, indicating a moderate toxicity profile. Ongoing monitoring and management of these side effects are essential to minimize risks to patients.
|book_text=VAL-083 represents an innovative approach to treating recurrent GBM, leveraging a unique mechanism of action that differs from other alkylating agents. Its effectiveness in patients with specific genetic markers, such as an unmethylated MGMT promoter, underscores the importance of targeted genetic testing in guiding GBM treatment. Further studies are crucial to confirm these preliminary findings and fully establish VAL-083's therapeutic potential and safety profile in GBM treatment.
|treatment_category=Other chemotherapy agents at recurrence
|overview=VAL-083 (Dianhydrogalactitol) is an innovative chemotherapy agent approved in China for treating recurrent Glioblastoma Multiforme (GBM) in patients with an unmethylated MGMT promoter, showing potential for improved median overall survival compared to lomustine. While ongoing clinical trials are evaluating its efficacy and safety, especially regarding its moderate toxicity profile, targeted genetic testing remains essential for optimizing treatment outcomes.}}

Next-Generation CAR T-Cell Therapy for GBM

2025-01-18T08:25:50Z

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{{TreatmentInfo
|drug_name=Next-Generation CAR T-Cell Therapy for GBM
|FDA_approval=In trial phase for GBM; FDA-approved for other cancers
|used_for=Recurrent Glioblastoma Multiforme (GBM)
|clinical_trial_phase=Phase 1 (INCIPIENT trial among others)
|common_side_effects=Fevers, altered mental status shortly after infusion, significant but manageable neurotoxicity
|OS_without=Median survival for recurrent GBM typically less than one year
|OS_with=Not fully established; dramatic and rapid tumor regression observed in initial patients
|PFS_without=Not specified
|PFS_with=Significant reduction in tumor size noted, durability of response under investigation
|usefulness_rating=4
|usefulness_explanation=Introduces a novel, highly personalized approach targeting mixed cell populations within GBM tumors. Early results demonstrate potential for substantial impact on tumor reduction and patient outcomes, indicating a promising direction for future GBM treatment strategies.
|toxicity_level=3
|toxicity_explanation=Includes expected side effects such as fevers and altered mental status post-infusion, with significant neurotoxicity that has been manageable in initial patients.
|book_text=Recent advancements in CAR T-cell therapy, particularly the innovative approach taken in the INCIPIENT trial, have shown promising early results for treating GBM. By targeting mixed cell populations within tumors and observing dramatic reductions in tumor size, this therapy represents a potential breakthrough in GBM treatment. While further research is needed to understand long-term effectiveness and manage side effects, these early findings provide hope for more effective GBM therapies.
Ben Williams book: Chimeric antigen receptor (CAR) T-cells are T-cells that have been genetically engineered,
commonly by the use of a retroviral vector, to express artificial receptors specifically
targeted to a chosen tumor-associated or tumor-specific antigen. CAR T-cells directed to
CD19 have been used with impressive success for B-cell acute lymphoblastic leukemia
(ALL), and tisagenlecleucel, an anti-CD19 CAR T-cell therapy was approved for this
indication on August 30, 2017. For glioblastoma, phase 1 CAR T-cell trials are currently
active, with preliminary outcomes now published for two of these trials, as discussed
below.
|links=https://www.massgeneral.org/news/press-release/clinical-trial-results-show-dramatic-regression-of-glioblastoma-after-next-generation-car-t-therapy

|overview=Next-Generation CAR T-Cell Therapy for recurrent Glioblastoma Multiforme (GBM) is currently in the trial phase and has shown promising early results, including significant tumor regression in initial patients. While FDA-approved for other cancers, this innovative therapy targets mixed cell populations in GBM tumors, offering hope for improved patient outcomes despite manageable side effects such as fevers and altered mental status.}}

Gamma Knife Radiosurgery

2025-01-18T08:25:36Z

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{{TreatmentInfo
|drug_name=Gamma Knife Radiosurgery (GKRS) for GBM
|FDA_approval=Yes
|used_for=Newly diagnosed Glioblastoma Multiforme (GBM)
|clinical_trial_phase=N/A (Established treatment modality)
|common_side_effects=Lower compared to traditional GBM treatments, with no significant radiation-induced toxicities reported in recent studies.
|OS_without=14-16 months with standard treatment.
|OS_with=Comparable to standard treatment, specifics depend on individual patient factors.
|PFS_without=Typically, tumors recur within 6 months of standard treatment.
|PFS_with=5.6 months reported in recent studies using fractionated sessions with Gamma Knife ICON.
|usefulness_rating=3
|treatment_category=Radiation
|usefulness_explanation=The primary advantage of GKRS for GBM lies in its lower toxicity profile, offering a safer treatment option for select patients without compromising on the progression-free survival (PFS) or overall survival (OS) rates.
|toxicity_level=2
|toxicity_explanation=GKRS, especially when utilized in a fractionated approach with the Gamma Knife ICON, presents a viable treatment option for GBM patients, emphasizing reduced side effects while maintaining efficacy.
|book_text=Gamma Knife Radiosurgery (GKRS) provides a novel approach for the management of newly diagnosed glioblastoma (GBM), emphasizing lower toxicity without significant alteration in progression-free or overall survival rates. This treatment modality, particularly with the advent of fractionated sessions using the Gamma Knife ICON, indicates a strategic shift towards maximizing patient safety and treatment tolerability. Further investigation in a prospective setting is warranted to fully ascertain the benefits and optimize treatment protocols.
|links=https://bmccancer.biomedcentral.com/articles/10.1186/s12885-022-10162-w
|overview=Gamma Knife Radiosurgery (GKRS) offers a promising and safer alternative for treating newly diagnosed Glioblastoma Multiforme (GBM), characterized by lower toxicity and comparable overall and progression-free survival rates compared to standard treatments. This established modality, particularly when using fractionated sessions with the Gamma Knife ICON, emphasizes patient safety while highlighting the need for further research to optimize treatment protocols.}}

Radiation via Monoclonal Antibodies

2025-01-18T08:25:22Z

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{{TreatmentInfo
|drug_name=Radiation via Monoclonal Antibodies
|FDA_approval=No
|used_for=Glioblastoma and potentially other high-grade glioma tumors
|clinical_trial_phase=Early to mid-stage clinical trials
|common_side_effects=Varies; can include fatigue, headache, localized reactions at infusion site
|OS_without=Standard treatments for GBM typically result in a median overall survival of 14-17 months
|OS_with=Early trials show median survival times from 56 weeks for recurrent GBM to up to 24.9 months in certain cohorts
|PFS_without=Median progression-free survival with standard treatments is about 6-9 months for GBM
|PFS_with=Some studies report mean progression-free survival up to 17.2 months, compared to 4-10 months for other treatments
|usefulness_rating=3
|usefulness_explanation=Shows promise for targeted radiation delivery to tumor cells with potential for sparing normal tissue and reducing side effects, but more research is needed for a definitive assessment
|treatment_category=Radiation
|toxicity_level=3
|toxicity_explanation=Potential risks are present and may be comparable to or slightly less than traditional treatments, with concerns about toxicity under investigation
|book_text=Radiation therapy via monoclonal antibodies introduces a targeted approach to delivering radiation to glioblastoma cells. This method involves attaching radioactive isotopes, such as iodine-131, to monoclonal antibodies that target specific antigens present on tumor cells but not on normal brain cells. The approach aims to maximize the therapeutic impact on the tumor while minimizing exposure and damage to surrounding healthy brain tissue. Duke University has been a pioneer in applying this technique. The major challenges include overcoming the blood-brain barrier and navigating the immunosuppressive tumor microenvironment. Early clinical trials have shown promising outcomes, with certain patient cohorts experiencing extended median survival times. However, the effectiveness and safety of this treatment are still under active investigation, highlighting the need for ongoing research and clinical trials to fully understand its potential and limitations.
|overview=Radiation via monoclonal antibodies is an experimental targeted treatment for glioblastoma and other high-grade gliomas, utilizing radioactive isotopes linked to antibodies that target tumor-specific antigens to enhance therapeutic efficacy while reducing collateral damage to healthy tissue. Early clinical trials have shown promising median survival benefits, but further research is needed to fully assess its safety and effectiveness, as it is currently not FDA-approved.}}

Proton Radiation Therapy

2025-01-18T08:25:08Z

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{{TreatmentInfo
|drug_name=Proton Beam Therapy (PBT)
|FDA_approval=Yes
|used_for=Glioblastoma and other cancers
|clinical_trial_phase=Ongoing research and clinical trials
|common_side_effects=Radiation dermatitis, temporary alopecia, radiation otitis, radiation necrosis (more prevalent in PBT group)
|OS_without=Data varies; traditional radiation therapies offer median OS of around 16-21 months for glioblastoma
|OS_with=High-dose PBT showed a median OS of 65.6 months for patients with radiation necrosis, and 26.9 months for patients without radiation necrosis in specific studies
|PFS_without=Standard radiation therapy PFS rates are lower compared to PBT
|PFS_with=Improved PFS observed with PBT, specific rates vary by study
|usefulness_rating=4
|toxicity_level=3
|treatment_category=Radiation
|category=Radiation
|toxicity_explanation=While acute radiation-related toxicities were equivalent to conventional radiation therapy, PBT has a higher prevalence of radiation necrosis, indicating a need for careful patient selection and management.
|book_text=Proton Beam Therapy (PBT) represents a more targeted form of radiation therapy for glioblastoma, distinguished by its use of protons instead of traditional photons. This method allows for precise targeting of the tumor, minimizing damage to surrounding brain tissue. Research indicates that high-dose PBT can offer significant survival advantages over conventional radiation therapy, although it comes with a higher risk of radiation necrosis. Recent studies have explored the efficacy and safety of PBT, highlighting its potential to improve patient outcomes while also noting the importance of addressing associated toxic...
|overview=Proton Beam Therapy (PBT) is an FDA-approved, targeted radiation treatment for glioblastoma and other cancers, offering potential survival advantages with improved progression-free survival rates compared to traditional therapies. While PBT minimizes damage to surrounding tissues, it is associated with a higher risk of radiation necrosis, necessitating careful patient selection and management.}}

Optune

2025-01-18T08:24:49Z

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{{TreatmentInfo
|drug_name=Optune (Optune Gio® for newer version)
|FDA_approval=Approved for newly diagnosed glioblastoma in October 2015; ongoing trials for broader applications
|used_for=Newly diagnosed glioblastoma, with trials for other cancers ongoing
|clinical_trial_phase=Phase 3 (EF-14 Trial); Phase 3 TRIDENT trial ongoing
|common_side_effects=Mild to moderate skin irritation beneath transducer arrays, thrombocytopenia, nausea, constipation, vomiting, fatigue, headache, convulsions, depression
|OS_without=16 months (control group in EF-14 Trial)
|OS_with=20.9 months (Optune plus temozolomide, final EF-14 analysis)
|PFS_without=4 months (control group in EF-14 Trial)
|PFS_with=7.1 months (Optune arm in EF-14 Trial); 6.7 months from diagnosis in updated analysis
|usefulness_rating=5
|toxicity_level=2
|toxicity_explanation=Most common adverse reaction is skin irritation at the device contact points; no increase in systemic adverse events
|book_text=Optune, now including Optune Gio® as its latest version, has shown significant survival benefits for newly diagnosed glioblastoma patients, especially when used in combination with temozolomide. It has been a part of a landmark phase 3 trial (EF-14) that demonstrated a considerable extension in both overall survival and progression-free survival. An ongoing TRIDENT trial is further investigating its efficacy in conjunction with radiation therapy and temozolomide from the onset of treatment. Optune represents a shift towards non-invasive cancer treatment modalities with reduced systemic toxicity and improved quality of life for patients.
|notes=Optune's significance is underscored by its addition to standard care for glioblastoma, showing remarkable survival benefits. It exemplifies the potential for non-invasive therapies in treating aggressive cancers, suggesting a paradigm shift in oncological treatments.
|treatment_category=Innovative Cancer Therapies
|overview=Optune, including its latest version Optune Gio®, is an innovative, non-invasive cancer therapy approved for newly diagnosed glioblastoma, demonstrating significant survival benefits when combined with temozolomide, as evidenced by the landmark EF-14 trial. With ongoing trials exploring its use for other cancers, Optune represents a potential paradigm shift in oncological treatments, offering improved quality of life and reduced systemic toxicity for patients.}}

EGFR inhibitors: Iressa, Tarceva, and Erbitux (gefitinib, erlotinib, and

2025-01-18T08:24:35Z

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{{TreatmentInfo
|drug_name=EGFR Inhibitors (Tarceva, Erbitux) in combination with Stupp Protocol
|FDA_approval=Yes, for other cancer types; off-label for GBM
|used_for=Glioblastoma Multiforme (GBM), particularly with EGF receptor overexpression or mutation
|clinical_trial_phase=Varied; includes studies with mixed outcomes
|common_side_effects=Specifics depend on individual drugs; can include rash, diarrhea, and potential infusion reactions
|OS_without=Median survival with standard Temodar protocol: approximately 14.1 months
|OS_with=Median survival with Tarceva addition: ranges from 15.3 to 19.3 months in studies, though one study showed only 8.6 months
|PFS_without=Not specified
|PFS_with=Improvement noted when EGFR inhibitors used in combination treatments, though highly variable
|usefulness_rating=3
|usefulness_explanation=EGFR inhibitors show potential when combined with standard treatments, suggesting a tailored approach based on genetic profiling of tumors may enhance efficacy. However, variability in outcomes indicates a need for further research and careful patient selection.
|toxicity_level=2
|toxicity_explanation=While generally well-tolerated, EGFR inhibitors can cause specific side effects, their severity depending on the drug and individual patient factors.
|book_text=The effectiveness of EGFR inhibitors like Tarceva and Erbitux for GBM treatment appears contingent on a combination approach and the genetic characteristics of the tumor, specifically EGFR overexpression and mutations in PTEN and PKB/AKT. Initial results suggest a moderate improvement in survival rates compared to standard protocols alone, but outcomes vary significantly. This underscores the importance of personalized medicine in GBM treatment, potentially enhancing effectiveness through the strategic combination of targeted therapies with established protocols. Further study is needed to refine these approaches and better predict patient response based on tumor genetics.
|overview=EGFR inhibitors like Tarceva and Erbitux, approved for various cancers, show potential in extending survival for glioblastoma multiforme (GBM) when combined with the Stupp Protocol, especially in patients with EGF receptor overexpression or mutations. However, clinical outcomes are variable and rely on genetic profiling, emphasizing the need for personalized treatment approaches and further research.}}

These three drugs, which have FDA approval for several different types of cancer, have
the common feature that they target a growth-signaling channel known as the epidermal
growth factor. Overexpression or mutation of EGF receptors is involved in the growth
many different kinds of cancer, including more than half of glioblastomas. In general, use
of these drugs as single agents has produced disappointing results, although occasional
long-term survivors have occurred. More promising results have occurred when EGFR
inhibitors have been used in combination with the Stupp protocol.

When Tarceva has been added to the standard Temodar protocol for newly diagnosed
patients, median survival was 15.3 months (N=97) in one study (72) and 19.3 months
(N=65) in a second study (73). The results of the second study were compared to two
previous phase II trials involving a similar patient population, in which Temodar was
combined with either thalidomide or accutane. Median survival for those trials was 14.1
months.

The moderately positive results of the just described trial are in conflict with a very
similar trial (N=27) conducted at the Cleveland Clinic (74). In that trial median survival
was only 8.6 months, notably worse than the outcomes obtained when temodar has been
used without tarceva. How the conflicting results can be reconciled is unclear.

Erbitux (also known as cetuximab) is a monoclonal antibody, which differs from Iressa
and Tarceva, which are small molecules, Because monoclonal antibodies are not believed
to cross the blood-brain barrier, the natural expectation is that Erbitux would be
ineffective against brain tumors. As a single agent, this seems to be true, as PFS-6 was
only 10% for patients with recurrent high-grade gliomas (75). But when Erbitux was
added during the radiation phase of the standard temozolomide protocol for 17 newly
diagnosed patients (76), 87% of patients were alive at the end of one year and 37% were
progression free. The median survival time had not been reached at the time of the report
(an abstract at a meeting). It is possibly important to note that some investigators believe
that radiation temporarily disrupts the blood-brain-barrier, which would allow a
monoclonal antibody such as erbitux to reach the tumor.

An important development for identifying patients likely to respond to Tarceva has come
from a study (77) of glioma patients whose tumor pathologies were also assessed for their
levels of a second protein called PKB/AKT. This is a signaling channel that results from
inactivation of the PTEN gene, a tumor suppressor gene commonly mutated in
glioblastomas. None of the tumors with high levels of PKB/AKT responded to treatment
with Tarceva, whereas 8 of 18 tumors with low levels did respond to the treatment. A
refinement of this approach tested for three different proteins: expression of PTEN,
expression of EGFR, and of a mutation of the EGFR protein known as EGFR variant III
(78). The level of EGFR was not related to clinical outcome, whereas the co-expression

of EGFR variant III and PTEN strongly predicted clinical outcome.

Because the inhibition of PKB/AKT should plausibly increase the effectiveness of EGFR
inhibitors, a treatment strategy now being tested is the combination of EGFR inhibitors
with rapamycin (trade name rapamune, generic name sirolimus), an existing drug used
for organ transplants to suppress the immune system and prevent organ rejection, but
which also inhibits mTOR complex 1, a tumor growth promoter downstream of AKT. A
phase I trial (79) combined Iressa with rapamycin for 34 patients (25 GBM) with
recurrent tumors; two patients had a partial tumor regression and 13 patients achieved
stable disease. PFS-6 was 24%. A second clinical trial (80) with 28 heavily pretreated
patients with low performance status (median Karnofsky score of 60) received either
Iressa or Tarceva in combination with rapamycin, with the result that 19% of patients had
tumor regression while 50% had stable disease, with a PFS-6 value of 25%. Yet a third
clinical trial (81) that combined tarceva and sirolimus for recurrent GBM had much worse
results, with PFS-6 value of only 3%.

The foregoing results of the use of EGFR inhibitors for GBM treatment range from
moderately positive to minimal efficacy. The reasons for this variability are not obvious,
although treatment efficacy is likely dependent on numerous genetic markers. Thus,
without a genetic analysis of individual tumors, it is hard to see a basis for recommending
their use.

One recent paper (83) of potential major importance has noted that tumors may not
respond to anti-EGFR drugs because of activation of the gene for a second growth factor
known as the insulin-like growth factor receptor I (IGF1R). IGF1R has also been
implicated as a source of resistance to tamoxifen and various other treatment agents. It is
noteworthy, therefore, that two of the supplements to be discussed, silibinin and
lycopene, are known to inhibit IGF-I. This suggests that silibinin and lycopene might
substantially increase the effectiveness of any treatment that relies on EGFR inhibition.
Metformin, a widely used diabetes drug, is also known to reduce the level of IGF-1,
currently is under investigation as a treatment for several different kinds of cancer.

An important issue is how the effectiveness of EGFR inhibitors are related to the findings
discussed earlier that metronomic schedules of Temodar produce a large survival
improvement for GBMs that have EGFR overexpression. All of the clinical trials
discussed in this section used the standard Temodar schedule, so it is unclear whether a
metronomic schedule might produce different outcomes.
}}

Chloroquine and Hydroxychloroquine

2025-01-18T08:24:22Z

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{{TreatmentInfo
|drug_name=Chloroquine and Hydroxychloroquine
|treatment_category=Repurposed Drugs
|book_text=In aseries of studies conducted in Mexico City (23, 24, 25) patients received the
traditional chemotherapy agent BCNU, with or without a 150 mg daily dose of
chloroquine (the equivalent of 250 mg chloroquine phosphate). The results were that
patients receiving chloroquine had a median survival time of 25-33 months, while those
receiving BCNU alone had a median survival time of 11 months. Chloroquine at the dose
used had no detectable toxicity. Because the cytotoxic mechanism of BCNU is similar to
that of Temodar, it seems likely that chloroquine should increase the efficacy of Temodar,
although this has yet to be demonstrated. One of several mechanisms by which
chloroquine makes chemotherapy more effective is that it inhibits autophagy, an
intracellular process that involves the cell digesting some of its internal parts to allow
repair of the damage caused by the chemotherapy.

Disappointingly, a multi-center phase I\/II trial testing the addition
of7hydroxychloroquine (which differs from chloroquine only by a single hydroxyl group)
to standard radiochemotherapy for newly diagnosed glioblastoma failed to show any
improvement in survival over historical averages. In the phase I safety and toxicity study,
all 3 subjects given 800 mg\/d hydroxychloroquine along with chemoradiation
experienced grade 3 or 4 neutropenia or thrombocytopenia, and 600 mg\/d was
determined to be the maximum tolerated dose. 76 patients were then treated at this dose
in the phase 2 cohort. Autophagy inhibition (the proposed mechanism of action) was not
consistently achieved at that dose, and patient survival (median OS 15.6 months, 2-year
survival of 25%) was not improved relative to historical control groups. The study
concluded that hydroxychloroquine was ineffective in this context at the maximum
tolerated dose (304).

Recent preclinical work (305) has shown increased reliance on autophagy and sensitivity

to chloroquine treatment in EGFR-overexpressing glioma cells, and any future trials with
chloroquine for high-grade gliomas may benefit from a subgroup analysis based on EGFR
status.
traditional chemotherapy agent BCNU, with or without a 150 mg daily dose of
chloroquine (the equivalent of 250 mg chloroquine phosphate). The results were that
patients receiving chloroquine had a median survival time of 25-33 months, while those
receiving BCNU alone had a median survival time of 11 months. Chloroquine at the dose
used had no detectable toxicity. Because the cytotoxic mechanism of BCNU is similar to
that of Temodar, it seems likely that chloroquine should increase the efficacy of Temodar,
although this has yet to be demonstrated. One of several mechanisms by which
chloroquine makes chemotherapy more effective is that it inhibits autophagy, an
intracellular process that involves the cell digesting some of its internal parts to allow
repair of the damage caused by the chemotherapy.

Disappointingly, a multi-center phase I\/II trial testing the addition
of7hydroxychloroquine (which differs from chloroquine only by a single hydroxyl group)
to standard radiochemotherapy for newly diagnosed glioblastoma failed to show any
improvement in survival over historical averages. In the phase I safety and toxicity study,
all 3 subjects given 800 mg\/d hydroxychloroquine along with chemoradiation
experienced grade 3 or 4 neutropenia or thrombocytopenia, and 600 mg\/d was
determined to be the maximum tolerated dose. 76 patients were then treated at this dose
in the phase 2 cohort. Autophagy inhibition (the proposed mechanism of action) was not
consistently achieved at that dose, and patient survival (median OS 15.6 months, 2-year
survival of 25%) was not improved relative to historical control groups. The study
concluded that hydroxychloroquine was ineffective in this context at the maximum
tolerated dose (304).

Recent preclinical work (305) has shown increased reliance on autophagy and sensitivity

to chloroquine treatment in EGFR-overexpressing glioma cells, and any future trials with
chloroquine for high-grade gliomas may benefit from a subgroup analysis based on EGFR
status.
|overview=Chloroquine and hydroxychloroquine are repurposed drugs that have shown varying effectiveness in enhancing chemotherapy for gliomas. While chloroquine demonstrated improved median survival times in conjunction with BCNU, multiple trials of hydroxychloroquine alongside chemoradiotherapy for glioblastoma failed to show significant survival benefits, highlighting the need for further research into patient-specific factors such as EGFR status.}}

Silibinin (an ingredient in Milk Thistle)

2025-01-18T08:24:09Z

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{{TreatmentInfo
|drug_name=Silibinin (Silymarin)
|FDA_approval=No
|used_for=Liver and biliary disorders, adjunct agent in cancer treatment
|clinical_trial_phase=Investigated primarily in hepatitis and cirrhosis; small studies in cancers such as acute lymphoblastic leukemia, prostate cancer, breast cancer, head and neck cancer, and hepatocellular carcinoma
|common_side_effects=Few reported; mainly gastrointestinal disturbances
|OS_without=Not specified
|OS_with=Not specified
|PFS_without=Not specified
|PFS_with=Not specified
|usefulness_rating=Under investigation; shown to have anti-cancer effects in laboratory studies
|notes=Silibinin, the active component of Milk Thistle, has shown potential in stabilizing cellular membranes, stimulating detoxification pathways, and inhibiting cancer cell growth in laboratory studies. It has a long history of use for liver and biliary disorders. Clinical trials in cancer are limited but suggest a potential role in enhancing chemotherapy efficacy and reducing toxicity.
|treatment_category=Dietary Supplement
|links=
* [Milk Thistle (PDQ®)–Health Professional Version - NCI](https://www.cancer.gov/about-cancer/treatment/cam/hp/milk-thistle-pdq)
|toxicity_level=Low
|toxicity_explanation=Silibinin is considered to have few side effects, with gastrointestinal disturbances being the most common.
|book_text=Silibinin (an ingredient of Milk Thistle)

Silymarin is an extract from the milk thistle plant that has been used extensively in
Europe as an antidote for liver toxicity, due to mushroom poisoning and overdoses of
tylenol. Its active ingredient is a molecule called silibinin. Recently a great deal of
laboratory research has shown it to have anti-cancer effects, which recently have been
reviewed (275). Like genistein and quercetin it is a tyrosine kinase inhibitor, but it
appears to have multiple other effects, including the inhibition of the insulin-like growth
factor (IGF) that contributes to the development of chemoresistance (276) (see the section
on tamoxifen), and the inhibition of angiogenesis (277). It also inhibits the 5-
lipoxygenase inflammatory pathway and suppresses nuclear factor kappa B, which is a
primary antagonist to apoptosis (278). It also appears to protect against common
chemotherapy toxicities (279), while at the same time increasing the effectiveness of
�chemotherapy.
|overview=Silibinin, an active component of Silymarin derived from Milk Thistle, is primarily used for liver and biliary disorders and is being investigated as an adjunct in cancer treatment. While it has not yet received FDA approval, research suggests it may enhance chemotherapy efficacy and reduce toxicity, with minimal side effects primarily related to gastrointestinal disturbances.}}

MN-166

2025-01-18T08:23:55Z

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{{TreatmentInfo
|drug_name=MN-166 (Ibudilast)
|FDA_approval=Approved in Japan for post-stroke complications and bronchial asthma; in late-stage clinical development for ALS, Progressive MS, DCM in other regions
|used_for=Experimental for ALS, Progressive MS, DCM, glioblastoma, CIPN, Long COVID, and substance use disorder
|clinical_trial_phase=Phase 3 for ALS and DCM, Phase 3-ready for Progressive MS, Phase 2 for glioblastoma, Long COVID, and substance use disorder
|common_side_effects=Not specified; has been used in Japan with a good post-marketing safety profile
|OS_with=Not specified
|OS_without=Not specified
|PFS_with=Not specified
|PFS_without=Not specified
|usefulness_rating=3 (awaiting research)
|toxicity_level=1
|notes=MN-166 (Ibudilast) is a small molecule compound that inhibits PDE4 and inflammatory cytokines including MIF. It is being developed by MediciNova for a broad range of conditions, including neurodegenerative diseases and glioblastoma, and has been in use in Japan for over 20 years. The drug is in various stages of clinical development in other regions, including Phase 3 for ALS and DCM, and Phase 2 for glioblastoma and substance use disorder.
|links=https://medicinova.com/clinical-development/core/mn-166/, https://www.globenewswire.com/news-release/2023/01/05/2584169/0/en/MediciNova-to-Meet-with-U-S-FDA-to-Discuss-Clinical-Development-of-a-Parenteral-Formulation-of-MN-166-ibudilast.html, https://www.globenewswire.com/news-release/2023/11/19/2584169/0/en/MediciNova-Announces-New-Data-and-Results-of-a-Phase-2.html
|treatment_category=Repurposed Drugs
|toxicity_explanation=MN-166 (Ibudilast) is generally regarded as having a low toxicity level due to its long-term use in Japan for other conditions. On a scale of 1 to 5, with 5 being the most toxic, it is rated at 1. This means that the drug is generally well-tolerated and the risk of severe side effects is relatively low. However, as MN-166 (Ibudilast) is still undergoing clinical trials for glioblastoma and other conditions outside of Japan, it's vital to consult closely with a healthcare provider before considering this treatment option.
|overview=MN-166 (Ibudilast) is an anti-inflammatory small molecule with FDA approval in Japan for conditions like post-stroke complications and bronchial asthma, currently undergoing late-stage clinical trials for ALS, Progressive MS, and DCM in other regions. With a good safety profile and low toxicity, it is also being explored experimentally for glioblastoma, Long COVID, and substance use disorder, although its overall usefulness rating remains at 3 pending further research.}}

Letrozole

2025-01-18T08:23:40Z

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{{TreatmentInfo
|drug_name=Letrozole
|FDA_approval=Yes (approved for breast cancer; not specifically approved for brain cancer yet)
|used_for=Experimental for glioblastoma; approved for hormone receptor-positive breast cancer
|clinical_trial_phase=Phase 2
|common_side_effects=Hot flashes, joint pain, nausea, increased risk of osteoporosis, fatigue
|OS_with=Not specified
|OS_without=Not specified
|PFS_with=Not specified
|PFS_without=Not specified
|usefulness_rating=3 - Under investigation
|toxicity_level=2.5
|notes=A collaborative study by the University of Cincinnati Cancer Center has initiated a Phase 2 trial to investigate the effectiveness of Letrozole in treating glioblastoma. This follows observations that certain breast cancer drugs, like Letrozole, which is used to treat hormone receptor-positive breast cancer, could be repurposed to inhibit the growth of glioblastoma cells by targeting estrogen receptors. The study is focused on understanding how Letrozole, when combined with standard therapy, affects the progression and treatment outcomes in glioblastoma patients.
|links=[University of Cincinnati article on Phase 2 brain tumor trial with Letrozole](https://www.uc.edu/news/articles/2024/02/collaborative-uc-cancer-center-team-opens-phase-2-brain-tumor-trial.html), [Brain Tomorrow's discussion on breast cancer drug Letrozole for glioblastoma](https://braintomorrow.com/breast-cancer-drug-letrozole-glioblastoma/)
|treatment_category=Repurposed Drugs
|toxicity_explanation=The treatment's toxicity level is rated at 2.5 out of a possible 5. This suggests that the treatment has some side effects, which can include hot flashes, joint pain, nausea, an increased risk of osteoporosis, and fatigue. However, these side effects are typically manageable and are considered moderate in comparison to other treatments. It's important to note that these side effects may not be experienced by everyone and can vary in intensity from person to person. Also, this drug is still in the experimental phase for glioblastoma and is not yet specifically approved for this type of brain cancer. The exact toxicity could change as more research is done.
|overview=Letrozole is an FDA-approved drug primarily used for hormone receptor-positive breast cancer, currently undergoing a Phase 2 clinical trial to assess its effectiveness in treating glioblastoma. While it has moderate side effects and is considered under investigation, early studies suggest potential benefits in repurposing this breast cancer treatment to inhibit glioblastoma cell growth through estrogen receptor targeting.}}

VT-122

2025-01-18T08:23:26Z

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{{TreatmentInfo
|drug_name=VT-122 (Propranolol and Etodolac combination)
|FDA_approval=No (VT-122 is an investigational combination of repurposed drugs; Propranolol and Etodolac are FDA-approved for other conditions)
|used_for=Investigational use in cancer treatment, specifically targeting cachexia in non-small cell lung cancer, hepatocellular carcinoma, and potentially glioblastoma
|clinical_trial_phase=Phase 2 (based on ongoing and completed trials for various cancer types)
|common_side_effects=Higher rates of thrombocytopenia, neutropenia, and anemia were observed in some studies
|OS_without=In the glioblastoma study, median overall survival was 9.2 months with low-dose TMZ alone
|OS_with=In the same glioblastoma study, median overall survival was 17.6 months with low-dose TMZ + VT-122
|PFS_with=Not specified; efficacy primarily reported in terms of overall survival and response rates in available studies
|usefulness_rating=4
|notes=VT-122, combining Propranolol and Etodolac, is under investigation for its potential to enhance survival and reduce cachexia in cancer patients. Preliminary results in glioblastoma suggest a notable improvement in overall survival and response rates when combined with low-dose temozolomide, indicating a promising direction for further research. The study's outcomes, including high response rates and an extended median survival time, highlight VT-122's potential, albeit with the need for more comprehensive trials to fully ascertain its benefits and safety profile.
|treatment_category=Repurposed Drugs
|links=
|toxicity_level=3
|toxicity_explanation=VT-122 has a toxicity level of 3 out of 5, This means it has moderate toxicity. Some people experiencing the treatment face significant side effects such as thrombocytopenia (low blood platelet count), neutropenia (low count of a type of white blood cell), and anemia (lower than normal level of red blood cells). This could results in increasing fatigue, bruising and bleeding easily, and being more susceptible to infections. However, the severity of these side effects may vary from person to person
|overview=VT-122 is an investigational combination of repurposed drugs Propranolol and Etodolac, targeting cachexia in cancer patients, particularly in non-small cell lung cancer, hepatocellular carcinoma, and glioblastoma. Preliminary studies indicate improved overall survival rates when paired with low-dose temozolomide, but further research is needed to evaluate its safety and efficacy.}}

Angiotensin-II Receptor Blockers (ARB)

2025-01-18T08:23:12Z

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{{TreatmentInfo
|drug_name=Angiotensin-II Receptor Blockers (ARB)
|FDA_approval=Yes (for hypertension; repurposed for cancer studies)
|used_for=Investigational use in glioblastoma for potential reduction of vasogenic edema and steroid-sparing effects
|clinical_trial_phase=Retrospective Studies
|common_side_effects=Varies by specific ARB; can include dizziness, hypotension, and renal function alteration
|OS_with=Not specified; studies have focused on steroid requirements and edema control
|PFS_with=Not specified; primary focus has been on edema reduction and potentially improved quality of life
|usefulness_rating=3
|notes=ARBs, primarily used for hypertension, have shown potential in reducing steroid dose requirements and peri-tumoral edema in glioblastoma patients in retrospective studies. While no direct survival benefit has been observed, the reduction in steroid dosage and control of edema suggest a potential supportive role in glioblastoma management. Further research, including a randomized phase 3 trial in France, is exploring the impact of ARBs like losartan on glioblastoma treatment outcomes.
|treatment_category=Hormones and Cancer Therapy
|links=
|toxicity_level=2
|toxicity_explanation=Angiotensin-II Receptor Blockers, primarily used for high blood pressure, have been repurposed for cancer studies, specifically for reducing swelling around brain tumors and lowering the need for steroids. Common side effects can include dizziness, low blood pressure, and alterations in kidney function. However, these are generally mild and manageable, hence the relatively low toxicity rating. While these drugs have shown potential in improving some symptoms, their impact on tumor growth or survival rate is still under investigation.
|book_text=Angiotensin-II is a peptide hormone produced from angiotensin-I by the action of
angiotensin converting enzyme (ACE). The main effect of angiotensin-II is
vasoconstriction and a resulting increase in blood pressure. Therefore ACE inhibitors and
angiotensin-II receptor blockers are used as anti-hypertensive drugs, especially in heart
disease. More recently these drugs have been repurposed for use in cancer studies.

A retrospective study published in 2012 (328) examined the steroid-sparing effects of
angiotensin-II inhibitors, incuding ACE inhibitors and angiotensin-II receptor blockers
(ARBs). Of a total cohort of 87 newly diagnosed glioblastoma patients, 29 patients were
identified who were treated prior to radiation for high blood pressure. 18 of these were
treated with either ACE inhibitors (n=3) or angiotensin-II receptor blockers (n=15).
Although no survival benefit with angiotensin-II inhibitors was observed in this study, the
18 patients treated with an angiotensin-II inhibitor required half the steroid dose
compared to all other patients in the study (mean prednisolone dose of 29 mg per day
versus 60 mg per day), and this difference remained significant in multivariate analysis
(p=0.003).

A later retrospective study by the same group published in January 2016 (329) focused
specifically on the angiotensin-II receptor blocker class of drugs and their effects on
vasogenic edema in glioblastoma patients. In this study, 11 patients taking angiotensin-II
receptor blockers (ARBs) for hypertension were compared with 11 matched patients with
similar age, tumor size, and tumor location, but not taking medication for hypertension.
There was a significant 66% reduction in the FLAIR ratio in the patients taking ARBs
compared to the matched patients not taking ARBs. As FLAIR signal can represent either
tumor infiltration or vasogenic edema, the nature of the peri-tumoral FLAIR signal was
assessed with apparent diffusion coeffient (ADC) mapping. Nine evaluable patients taking
28

ARBs had a 34% reduction in ADC ratios compared to their matched controls not taking
ARBs, confirming the ability of this class of drugs to reduce peri-tumoral edema.

A 2015 study, also by the group in France, suggests angiotensin-II inhibitors (including
ACE inhibitors and ARBs) may also lead to superior survival outcomes (330). In this
study, 81 GBM patients were included. Seven of these patients were taking ACE inhibitors
and 19 were taking ARBs for hypertension. The 26 patients using angiotensin-II
inhibitors had increased progression-free and overall survival (8.7 and 16.7 months)
compared to the patients not taking these drugs (7.2 and 12.9 months). Use of
angiotensin-II inhibitors was a significant positive prognostic factor for both PFS and OS
in multivariate analysis.

A randomized phase 3 trial in France (NCT01805453) has recently completed
recruitment, and is testing the influence of losartan (an ARB) versus placebo on the
steroid dose required to control edema on the last day of radiotherapy. Another drug in
this class, telmisartan, has superior penetration into the central nervous system (331) and
may therefore be a better choice.

See Chapter 13 for a discussion of Angiotensin system inhibitors plus Avastin
|overview=Angiotensin-II Receptor Blockers (ARBs), initially approved for hypertension, are being investigated for their potential to reduce vasogenic edema and steroid requirements in glioblastoma patients, showing promising effects in retrospective studies despite no direct survival benefits reported. Ongoing research, including a randomized phase 3 trial, aims to further explore the supportive role of ARBs in glioblastoma management.}}

Gleevec (Imatinib)

2025-01-18T08:22:57Z

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{{TreatmentInfo
|drug_name=Gleevec (Imatinib)
|FDA_approval=Yes (for chronic myelogenous leukemia and other cancers, not specifically approved for gliomas)
|used_for=Investigational use in gliomas, specifically targeting overexpression of platelet-derived growth factor receptor (PDGFR)
|clinical_trial_phase=Exploratory/Investigational (Specific phase for gliomas not provided)
|common_side_effects=Varies; for leukemia treatment includes fluid retention, nausea, muscle cramps, rashes, and fatigue. Brain tumor studies may have different profiles due to combination treatments and patient population.
|OS_with=Not applicable; studies focusing on PFS-6 as a primary endpoint
|PFS_with=PFS-6 value was 53% in a restricted patient population with overexpression of PDGFR
|usefulness_rating=3
|notes=Gleevec, known for its role in leukemia treatment, has shown potential in inhibiting glioma growth due to its targeting of PDGF. Its effectiveness in brain tumors has been limited, possibly due to issues crossing the blood-brain barrier and various resistance mechanisms. Its use has been explored in patients with recurrent tumors and PDGFR overexpression, showing some promise in early research.
|treatment_category=Other Chemotherapy and Cancer Drugs
|links=
|toxicity_level=3
|toxicity_explanation=Gleevec (Imatinib) is at a moderate toxicity level. This is because while it does have side effects such as fluid retention, nausea, muscle cramps, rashes, and fatigue, these are common to most treatments and they vary from patient to patient. Also, it has not been specifically approved for glioma treatment, indicating that it might have unexpected results, slightly increasing the risk factor. However, it has shown some potential benefits in early research, hence the moderate, not high, toxicity rating.
|book_text=Gleevec (also known as imatinib), a small molecule which targets a specific gene involved
in the growth of a form of leukemia, received a great deal of publicity because of its
unprecedented effectiveness. As will be discussed later, this general strategy of
identifying the growth signals for tumor growth and then targeting those signals, or their
receptors, is one of the major new areas in cancer research. Such growth signaling
channels often are involved in several different types of cancer. Although Gleevec was
developed specifically for chronic myelogenous leukemia, it also has been shown to
inhibit a more general type of growth signal, platelet-derived growth factor (PDGF),
which is also involved in the growth of gliomas and other forms of cancer (e.g., small-
cell lung cancer). Laboratory research has supported the importance of this similarity in
that gleevec has been shown to strongly inhibit glioma growth, with the result that there
now have been a number of studies reporting its use with high-grade gliomas.

The generally disappointing results using gleevec for brain tumors may have occurred

for several different reasons. It may not readily cross the blood-brain-barrier, and it may
engender different mechanisms of resistance than other treatment agents. In the study of
gleevec for leukemia, for example, high levels of autophagy have been observed, which
can be inhibited by the concurrent use of chloroquine or other autophagy inhibitors.

An important variation in the use of gleevec was to restrict its usage to patients with
recurrent tumors who tested positive for overexpression of the platelet-derived growth
factor receptor (90). PDGFR is overexpressed in 50-65% of tumors, especially tumors

labeled secondary glioblastomas, which are believed to have evolved from lower-grade
tumors (in contrast to de novo glioblastomas that occur without such evolution). For this
restricted patient population, the PFS-6 value was 53%.
|overview=Gleevec (Imatinib) is an FDA-approved drug primarily used for chronic myelogenous leukemia, with investigational use in gliomas targeting overexpression of platelet-derived growth factor receptor (PDGFR). While it has shown some promise in inhibiting glioma growth, especially in patients with PDGFR overexpression, its effectiveness is limited by challenges such as crossing the blood-brain barrier and varying resistance mechanisms.}}

Bevacizumab (Avastin)

2025-01-18T08:22:44Z

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{{TreatmentInfo
|drug_name=Procarbazine
|FDA_approval=Yes
|used_for=Glioblastoma
|clinical_trial_phase=Not specified
|common_side_effects=Hematological toxicity, nausea, and neurological effects
|OS_with=Not specified
|usefulness_rating=3
|notes=Combination of Temodar and procarbazine showed a high percentage of tumor regressions, suggesting effectiveness.
|treatment_category=Other Chemotherapy and Cancer Drugs
|toxicity_level=4
|toxicity_explanation=The drug Procarbazine is considered quite toxic. This rating is based on the common side effects like hematological toxicity, which refers to potential harm to your blood cells, nausea, and neurological effects such as headache or dizziness. These side effects are relatively common and could significantly affect your day-to-day life. Remember, all treatments come with potential risks, and it's important to discuss these with your doctor.
|book_text=Temodar has also been combined with procarbazine (64). While the report of that study
did not include the PFS-6 statistic, it did report an unusually high percentage of tumor
regressions, suggesting that this combination might be effective.
|overview=Procarbazine is an FDA-approved chemotherapy drug primarily used for treating glioblastoma, known for its effectiveness when combined with Temodar, as evidenced by a high percentage of tumor regressions. However, it carries a toxicity level of 4, with common side effects including hematological toxicity, nausea, and neurological effects that can significantly impact daily life.}}

Procarbazine

2025-01-18T08:22:32Z

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Platinum Compounds

2025-01-18T08:22:18Z

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{{TreatmentInfo
|drug_name=Platinum Compounds
|FDA_approval=Yes
|used_for=Glioblastoma
|clinical_trial_phase=Various, including Phase II
|common_side_effects=Nephrotoxicity, ototoxicity, and neurotoxicity
|OS_with=Not specified
|usefulness_rating=3
|notes=Combining Temodar with cisplatin has shown improved PFS-6 in recurrent tumors. A protocol combining Temodar, cisplatin, and etoposide reported median survival of 25 months.
|treatment_category=Other Chemotherapy and Cancer Drugs
|toxicity_level=4
|toxicity_explanation=The treatment with Platinum Compounds (Cisplatin) is considered relatively high in toxicity due to potential side effects like kidney damage (Nephrotoxicity), hearing loss (ototoxicity), and nervous system damage (neurotoxicity). It's important for patients to discuss these risks with their healthcare provider before starting therapy. A toxicity level of 4 out of 5 means this treatment carries significant risks, but it may be necessary for managing glioblastoma.
|book_text=An improvement in results relative to those obtained with Temodar alone has also been
reported when Temodar has been combined with cisplatin. In a pair of clinical studies
performed in Italy (61, 62) with patients with recurrent tumors, the PFS-6 was 34% and
35%. A treatment protocol with newly diagnosed patients that also seems to have
produced better results than Temodar as a single agent combined Temodar with both
cisplatin and etoposide (VP-16), given through the carotid artery (63). Cisplatin and
etoposide were given after surgery and continued for three cycles spaced every 3 weeks
apart, followed by the standard protocol of radiation plus low-dose Temodar, then
high-dose Temodar on the schedule of days 1-5 of every month. For 15 patients studied,
median survival was 25 months.
|overview=Platinum Compounds, particularly cisplatin, are FDA-approved chemotherapy agents used in the treatment of glioblastoma, showing improved progression-free survival when combined with Temodar and etoposide, despite a high toxicity profile characterized by nephrotoxicity, ototoxicity, and neurotoxicity. Clinical trials indicate a median survival of 25 months for patients receiving this combination therapy, though significant risks must be discussed with healthcare providers.}}

BCNU (Carmustine) and Gliadel (Carmustine Wafers)

2025-01-18T08:22:04Z

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{{TreatmentInfo
|drug_name=BCNU (Carmustine) and Gliadel (Carmustine Wafers)
|FDA_approval=Yes
|used_for=High-grade gliomas
|clinical_trial_phase=Phase III (Europe for Gliadel)
|common_side_effects=Low blood counts, pulmonary problems, infection, and seizures for Gliadel
|OS_with=Gliadel: 13.9 months median survival; Combination with TMZ: Median survival ranges from 17 to 20.7 months
|usefulness_rating=4
|toxicity_level=4
|toxicity_explanation=The combination of BCNU and Gliadel Wafers in treatment for glioblastoma is assigned a toxicity level of 4, this is relatively high on a scale of 1 to 5. This means that the treatment has serious side effects which may include low blood counts, pulmonary problems, infections, and seizures. Despite these side effects, the improvement in survival rates may make this treatment an important option for many patients. However, managing these side effects could potentially be challenging and may significantly impact the quality of life. It's important to discuss these risks and potential benefits with your healthcare provider.
|book_text=The combination of Temodar with BCNU, the traditional chemotherapy for glioblastomas,
has also been studied, but has been complicated by issues of toxicity and the optimal
schedule of dose administration for the two drugs. However, a recent published report
involving patients with tumors recurring after radiation but no prior chemotherapy failed
to show any benefit of combining BCNU with Temodar, compared to Temodar alone, as
the PFS-6 for the combination was only 21%, accompanied by considerable toxicity (53).

An important variation in the use of BCNU has been the development of polymer wafers
known as gliadel. A number of such wafers are implanted throughout the tumor site at the
time of surgery. BCNU then gradually diffuses from the wafers into the surrounding
brain. A possible problem with the treatment is that the drug will diffuse only a small
distance from the implant sites, and thus fail to contact significant portions of the tumor.
However, a phase III clinical trial has demonstrated that survival time for recurrent high-
grade gliomas is significantly increased by the gliadel wafers relative to control subjects
receiving wafers without BCNU, although the increase in survival time, while

statistically significant, was relatively modest (54). Probably the best estimate of the
benefit of gliadel as an initial treatment comes from a randomized clinical trial,
conducted in Europe (55), which reported a median survival of 13.9 months for patients
receiving gliadel compared to a median survival of 11.6 months for patients implanted
with placebo wafers. As with other forms of chemotherapy, larger differences were
evident for long-term survival. After a follow-up period of 56 months, 9 of 120 patients
who received gliadel were alive, compared to only 2 of 120 of those receiving the

placebo. However, the results were not reported separately for glioblastomas vs. other
high-grade gliomas, suggesting that the outcome results would have been more modest
for the glioblastoma patients alone.

When gliadel has been combined with the standard TMZ + radiation protocol, survival
time seems to be significantly improved, as assessed in three different retrospective
clinical studies. In the first, from the Moffitt Cancer Center in Florida (56), the
combination produced a median overall survival of 17 months, and a 2-year survival rate
of 39%. In a second clinical trial reported by Johns Hopkins, where gliadel was
developed (57), 35 patients receiving the combination had a median survival time of 20.7
months and a 2-year survival of 36%. In a third trial conducted at Duke University (58),
36 patients receiving gliadel in addition to the standard TMZ protocol had a median
survival of 20.7 months and a 2-year survival of 47%. The Duke cohort also received
rotational chemotherapy (which included TMZ) subsequent to radiation. It is important
to keep in mind that patients eligible to receive gliadel must have operable tumors, which
excludes patients who have received a biopsy only and have a generally poorer prognosis
as a result. The effect of this selection bias is difficult to evaluate but it is likely to
account for a significant fraction of the improvement in survival time when gliadel
+TMZ is compared to TMZ alone.

A major advantage of gliadel is that it avoids the systemic side effects of intravenous
BCNU, which can be considerable, not only in terms of low blood counts but also in
terms of a significant risk of major pulmonary problems. But gliadel produces its own
side effects, including an elevated risk of intracranial infections and seizures. However,
the lack of systemic toxicity makes gliadel a candidate for various drug combinations.
Especially noteworthy is a recent phase II trial with 50 patients with recurrent tumors
that combined gliadel with 06-BG, a drug that depletes the MGMT enzyme involved in
repair of chemotherapy-induced damage, but also causes unacceptable bone marrow
toxicity when chemotherapy is given systemically. Survival rates at six months, one year

and two years were 82%, 47%, and 10%, respectively (59) which seems notably better than
the earlier clinical trial with recurrent tumors using gliadel without the 06-BG, in which
the corresponding survival rates were 56%, 20%, and 10%. Median survivals were also
notably improved by the addition of 06-BG (50.3 weeks versus 28 weeks).

The combination of Temodar with BCNU, the traditional chemotherapy for glioblastomas,
has also been studied, but has been complicated by issues of toxicity and the optimal
schedule of dose administration for the two drugs. However, a recent published report
involving patients with tumors recurring after radiation but no prior chemotherapy failed
to show any benefit of combining BCNU with Temodar, compared to Temodar alone, as
the PFS-6 for the combination was only 21%, accompanied by considerable toxicity (53).

An important variation in the use of BCNU has been the development of polymer wafers
known as gliadel. A number of such wafers are implanted throughout the tumor site at the
time of surgery. BCNU then gradually diffuses from the wafers into the surrounding
brain. A possible problem with the treatment is that the drug will diffuse only a small
distance from the implant sites, and thus fail to contact significant portions of the tumor.
However, a phase III clinical trial has demonstrated that survival time for recurrent high-
grade gliomas is significantly increased by the gliadel wafers relative to control subjects
receiving wafers without BCNU, although the increase in survival time, while

statistically significant, was relatively modest (54). Probably the best estimate of the
benefit of gliadel as an initial treatment comes from a randomized clinical trial,
conducted in Europe (55), which reported a median survival of 13.9 months for patients
receiving gliadel compared to a median survival of 11.6 months for patients implanted
with placebo wafers. As with other forms of chemotherapy, larger differences were
evident for long-term survival. After a follow-up period of 56 months, 9 of 120 patients
who received gliadel were alive, compared to only 2 of 120 of those receiving the

placebo. However, the results were not reported separately for glioblastomas vs. other
high-grade gliomas, suggesting that the outcome results would have been more modest
for the glioblastoma patients alone.

When gliadel has been combined with the standard TMZ + radiation protocol, survival
time seems to be significantly improved, as assessed in three different retrospective
clinical studies. In the first, from the Moffitt Cancer Center in Florida (56), the
combination produced a median overall survival of 17 months, and a 2-year survival rate
of 39%. In a second clinical trial reported by Johns Hopkins, where gliadel was
developed (57), 35 patients receiving the combination had a median survival time of 20.7
months and a 2-year survival of 36%. In a third trial conducted at Duke University (58),
36 patients receiving gliadel in addition to the standard TMZ protocol had a median
survival of 20.7 months and a 2-year survival of 47%. The Duke cohort also received
rotational chemotherapy (which included TMZ) subsequent to radiation. It is important
to keep in mind that patients eligible to receive gliadel must have operable tumors, which
excludes patients who have received a biopsy only and have a generally poorer prognosis
as a result. The effect of this selection bias is difficult to evaluate but it is likely to
account for a significant fraction of the improvement in survival time when gliadel
+TMZ is compared to TMZ alone.

A major advantage of gliadel is that it avoids the systemic side effects of intravenous
BCNU, which can be considerable, not only in terms of low blood counts but also in
terms of a significant risk of major pulmonary problems. But gliadel produces its own
side effects, including an elevated risk of intracranial infections and seizures. However,
the lack of systemic toxicity makes gliadel a candidate for various drug combinations.
Especially noteworthy is a recent phase II trial with 50 patients with recurrent tumors
that combined gliadel with 06-BG, a drug that depletes the MGMT enzyme involved in
repair of chemotherapy-induced damage, but also causes unacceptable bone marrow
toxicity when chemotherapy is given systemically. Survival rates at six months, one year
and two years were 82%, 47%, and 10%, respectively (59) which seems notably better than
the earlier clinical trial with recurrent tumors using gliadel without the 06-BG, in which
the corresponding survival rates were 56%, 20%, and 10%. Median survivals were also
notably improved by the addition of 06-BG (50.3 weeks versus 28 weeks).

|notes=While Gliadel wafers alone offer modest improvement, combining them with the standard TMZ protocol seems to significantly improve outcomes.
|treatment_category=Other Chemotherapy and Cancer Drugs
|overview=BCNU (Carmustine) and Gliadel (Carmustine Wafers) are FDA-approved treatments for high-grade gliomas, with a median survival of 13.9 months for Gliadel alone and 17 to 20.7 months when combined with Temozolomide (TMZ). While Gliadel wafers provide a localized treatment option that minimizes systemic side effects, they carry significant risks, such as low blood counts and seizures, and are associated with a toxicity level of 4 out of 5.}}

CCNU (Lomustine)

2025-01-18T08:21:49Z

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{{TreatmentInfo
|drug_name=CCNU (Lomustine)
|FDA_approval=Yes
|used_for=Glioblastoma
|clinical_trial_phase=Phase 3 (Germany)
|common_side_effects=Hematological toxicity, nausea, vomiting, and pulmonary toxicity
|OS_with=23 months median survival, with 47% at 2 years
|usefulness_rating=4
|notes=A combination of TMZ with CCNU showed promising results including a 5-year survival rate of 16% among a small patient cohort. MGMT methylation status significantly influenced outcomes.
|treatment_category=SOC Chemotherapy
|toxicity_level=4
|toxicity_explanation=The toxicity level of CCNU is quite high due to several common side effects. Most notably, it can cause hematological toxicity, which means it can damage your blood cells and affect your body's ability to fight infections and clot properly. It can also cause nausea, vomiting, and pulmonary toxicity, which can lead to lung damage. On a scale from 1 to 5, with 5 being the most toxic, CCNU is rated as a 4. However, despite these side effects, the treatment showed promising results in a clinical trial.
|book_text=A report from Germany combined TMZ with CCNU (lomustine), the nitrosourea
component of the PCV combination (52). Patients (N=39) received CCNU on day 1 of
each 6-week cycle, and TMZ on days 2-6. Eight patients received intensified doses of
both drugs, with somewhat better survival results (but with substantially increased
toxicity). For present purposes, the results of all patients are aggregated. Median survival
time was 23 months, and survival rates were 47%, 26%, 18%, and 16% at 2, 3, 4, and5
years, respectively. Four of the 39 patients had no recurrence at the 5-year mark. Only 23
of the 39 patients were assessable for the status of the MGMT gene. Those with
methylated MGMT had a median survival of 34 months, while those with unmethylated
MGMT had a median survival of only 12.5 months.

These results, including a 5-year survival rate of 16%, are among the best yet reported,
albeit with a relatively small number of patients. But it also should be appreciated that
patients who suffered a recurrence received extensive salvage therapy of various types,
which may have contributed substantially to survival time. The addition of CCNU to
standard therapy for newly diagnosed glioblastoma is currently being tested in a phase 3
trial in Germany.
|overview=CCNU (Lomustine) is an FDA-approved chemotherapy drug used for treating glioblastoma, demonstrating a median survival of 23 months with a 47% two-year survival rate; however, it is associated with significant side effects, including hematological toxicity, nausea, and pulmonary toxicity, which contribute to its high toxicity level rating of 4. A clinical trial in Germany has shown promising results, particularly in patients with methylated MGMT, indicating potential benefit when used in combination with TMZ.}}

MDNA55

2025-01-18T08:21:35Z

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{{TreatmentInfo
|drug_name=MDNA55
|FDA_approval=No
|used_for=Recurrent malignant gliomas
|clinical_trial_phase=Early phase trials
|common_side_effects=Not specified in the provided text
|OS_with=Not specified in the provided text
|PFS_with=Not specified in the provided text
|usefulness_rating=3
|notes=MDNA55, a fusion of IL-4 and Pseudomonas exotoxin A, targets cells with high IL-4R expression, common in tumor tissue. Preliminary data shows significant efficacy with a 56% response rate and a 20% complete response rate in recurrent glioblastoma patients treated with a single infusion, highlighting potential as a highly effective treatment.
|treatment_category=Antibody-Drug Conjugates and other protein-drug conjugates
|links=
|toxicity_level=2.5
|toxicity_explanation=The treatment, MDNA55, is in its early phase of trials, meaning that its potential side effects are still being evaluated. Currently, it's not fully approved by the FDA and exact toxicity is not specified. However, MDNA55 is designed to target cells common in tumor tissue, creating a high potential for effectiveness with fewer harmful effects on healthy tissue. It has shown significant positive response rates, suggesting a manageable toxicity profile. Nevertheless, every treatment carries some risk, and potential side effects might still be discovered. The toxicity rating of 2.5 out of 5 indicates a moderate risk of toxic side effects at this point in time.
|overview=MDNA55 is an investigational treatment for recurrent malignant gliomas that combines IL-4 and Pseudomonas exotoxin A, targeting tumor cells with high IL-4R expression. Early-phase trials have shown promising efficacy, with a 56% response rate and a 20% complete response rate, though it remains unapproved by the FDA and its side effects are still under evaluation.}}