Glioblastoma Treatments - User contributions [en]

Proton Pump Inhibitors

2024-11-12T18:58:34Z

69.163.248.232:

{{TreatmentInfo
|drug_name=Proton Pump Inhibitors (e.g., Lansoprazole, Nexium)
|FDA_approval=Yes (for heartburn and acid-related issues)
|used_for=Investigational use in enhancing sensitivity of cancer cells to chemotherapy
|clinical_trial_phase=Preclinical studies and observational studies in animals and humans
|common_side_effects=Common PPI side effects include headache, nausea, diarrhea, abdominal pain, fatigue, and dizziness
|OS_without=Not specified
|OS_with=Studies suggest PPIs may improve progression-free survival in cancer treatment
|PFS_without=7.5 months in metastatic breast cancer patients receiving only chemotherapy
|PFS_with=9.5 months with 100 mg Nexium; 10.9 months with 80 mg Nexium
|usefulness_rating=3
|notes=PPIs, commonly used for acid-related stomach issues, may suppress tumor growth by disrupting cancer cells' acid extrusion. Pre-treatment with PPIs has shown to sensitize cancer cells to cytotoxic drugs and improve treatment outcomes in preliminary studies. Further research is necessary to understand the optimal dosing and clinical efficacy in human cancer treatment.
|treatment_category=Repurposed Drugs
|links=
|toxicity_level=2
|toxicity_explanation=The drug being tested, a Proton Pump Inhibitor, is commonly used for heartburn and acid-related issues, and is now being tested for its potential benefits in treating cancer. Its side effects include common, non-severe symptoms like headache, nausea, diarrhea, abdominal pain, fatigue, and dizziness. Although these can be uncomfortable, they are manageable and often temporary. Thus, we rate its toxicity a 2 out of 5. However, the drug is still under preclinical and observational studies for its use in cancer treatment, meaning its effects are not fully understood. Always consult with your physician when considering new treatments.
}}

Methadone

2024-11-12T18:58:23Z

69.163.248.232:

{{TreatmentInfo
|drug_name=Methadone (D,L-methadone)
|FDA_approval=Yes (for pain management and replacement therapy for addiction)
|used_for=Investigational use in glioblastoma treatment for its chemosensitizing effects
|clinical_trial_phase=Preclinical studies and a retrospective safety and tolerability study in glioma patients
|common_side_effects=Nausea, constipation (obstipation); side effects commonly resolved after one month of therapy
|OS_without=Not specified in provided details
|OS_with=In a study with newly diagnosed GBM patients, progression-free survival at 6 months was 91% when methadone was added to the standard of care
|PFS_without=Not specified
|PFS_with=Significant in the context of preliminary findings from retrospective studies
|usefulness_rating=3
|notes=Methadone, primarily known for severe pain management and opioid replacement therapy, has demonstrated potential as a chemosensitizer in glioma cells through in vitro studies and mouse models. It exhibits this effect by inhibiting the activity of the DNA-repair enzyme MGMT and sensitizing cells to chemotherapy, along with blocking adenyl cyclase leading to decreased expression of anti-apoptotic proteins. Early clinical data suggest a positive impact on progression-free survival in glioblastoma patients when combined with standard treatments, although further research is needed to confirm efficacy and optimal dosing.
|treatment_category=Repurposed Drugs
|links=
|toxicity_level=2
|toxicity_explanation=The toxicity level for Methadone, when used for investigational purposes in treating glioblastoma, is relatively low. It is well-established for its use in pain management and replacement therapy for addiction, known to have common side effects such as nausea and constipation, which usually resolve after one month. It has been found to have potential as a chemosensitizer in glioma cells, meaning that it makes the cancer cells more sensitive to chemotherapy. However, this use is currently in the research and investigative stage. It's important to note that the side effects may vary among individuals, and adequate supervision from healthcare providers is necessary during administration of this treatment.
}}

Keppra

2024-11-12T18:58:11Z

69.163.248.232:

{{TreatmentInfo
|drug_name=Keppra (Levetiracetam)
|FDA_approval=Yes (as an anti-seizure medication, 1999)
|used_for=Seizure prevention in brain tumor patients, potential sensitizer for glioblastoma cells to temozolomide chemotherapy
|clinical_trial_phase=Retrospective studies and laboratory research
|common_side_effects=Common side effects associated with Keppra include fatigue, dizziness, and mood changes, but it is generally well-tolerated in the context of brain tumor treatment.
|OS_without=Median OS for glioblastoma patients not taking Keppra: 16.7 months
|OS_with=Median OS for glioblastoma patients taking Keppra during chemotherapy: 25.7 months
|PFS_without=Median PFS for patients not taking Keppra: 6.7 months
|PFS_with=Median PFS for patients taking Keppra: 9.4 months
|usefulness_rating=4
|notes=Keppra has become a prevalent choice for seizure prevention in brain tumor patients, with emerging evidence suggesting it can also enhance the efficacy of temozolomide chemotherapy by inhibiting MGMT enzyme activity. Significant increases in progression-free and overall survival were observed in patients receiving Keppra alongside chemotherapy in a retrospective study. Further research is needed to understand the full scope of benefits and whether they extend to patients with unmethylated MGMT status.
|treatment_category=Repurposed Drugs
|links=
|toxicity_level=2
|toxicity_explanation=Keppra (Levetiracetam) is generally well-tolerated when used in the treatment of glioblastoma. Its side effects including fatigue, dizziness, and mood changes are fairly mild. However, like all medication, it does come with some level of toxicity which is why it's ranked at a 2 on a scale of 1 to 5. It's important to always discuss potential side effects with your healthcare provider to ensure this treatment is a good fit for you.
}}

Disulfiram

2024-11-12T18:58:00Z

69.163.248.232:

{{TreatmentInfo
|drug_name=Disulfiram (Antabuse)
|FDA_approval=Yes (for preventing alcohol consumption)
|used_for=Exploratory treatment for GBM in combination with temozolomide and potentially copper gluconate
|clinical_trial_phase=Phase I pharmacodynamics trial at Washington University, ongoing research
|common_side_effects=At higher doses: delirium and peripheral motor neuropathy; minimal toxicity when alcohol is not consumed
|OS_without=Not specified
|OS_with=Early results suggest potential efficacy in enhancing chemotherapy response; ongoing trials
|PFS_without=Not specified
|PFS_with=Initial results indicate a need for dosage optimization to balance efficacy and side effects
|usefulness_rating=3
|notes=Disulfiram, a drug traditionally used to prevent alcohol consumption, shows promise in GBM treatment through mechanisms such as blocking glycoprotein pumps and inhibiting MGMT enzyme and metalloproteinase activity. It's believed to inhibit the growth of cancer stem cells, a major source of treatment failures. Its anticancer effects may be potentiated by concurrent use of copper gluconate. Current trials are investigating optimal dosing and combination strategies to maximize therapeutic outcomes.
|treatment_category=Repurposed Drugs
|links=
|toxicity_level=2
|toxicity_explanation=Disulfiram shows a relatively low toxicity for treating Glioblastoma, especially when no alcohol is consumed. This means it could be a safer choice for treatment. Potential side effects like delirium and peripheral motor neuropathy were only reported at higher dosages. However, ongoing research is important to maximize therapeutic outcomes and minimize any potential side effects.
}}

Chloroquine

2024-11-12T18:57:48Z

69.163.248.232:

{{TreatmentInfo
|drug_name=Chloroquine and Hydroxychloroquine
|FDA_approval=No (for glioblastoma treatment)
|used_for=Glioblastoma, in combination with traditional chemotherapy agents
|clinical_trial_phase=Reviewed in recent meta-analyses and studies
|common_side_effects=Generally well-tolerated; specific studies noted minimal impact on adverse event incidence
|OS_without=BCNU alone: median survival of 11 months
|OS_with=Chloroquine with BCNU: median survival significantly improved to 25-33 months; recent meta-analysis supports decreased mortality and improved survival time in glioblastoma patients
|PFS_without=Not specified in the recent analysis
|PFS_with=Not directly specified; chloroquine shown to induce remission rates without increasing adverse events significantly
|usefulness_rating=4
|notes=Recent studies highlight Chloroquine's potential in glioblastoma treatment, significantly improving survival rates when combined with chemotherapy. Chloroquine acts as an autophagy inhibitor, potentially enhancing chemotherapy's effectiveness by inhibiting a survival mechanism in cancer cells. Hydroxychloroquine's efficacy at the maximum tolerated dose has not shown improvement in survival, suggesting Chloroquine as the more promising agent for future clinical trials, especially considering tumor genetic profiles such as EGFR status.
|treatment_category=Repurposed Drugs
|toxicity_level=1
|book_text=Chloroquine and Hydroxychloroquine

In a series 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.
|links=
* [Chloroquine Supplementation for the Treatment of Glioblastoma: A Meta-analysis of Randomized Controlled Studies - PubMed](https://pubmed.ncbi.nlm.nih.gov/36409625)
* [Chloroquine in Cancer Therapy: A Double-Edged Sword of Autophagy - AACR Journals](https://aacrjournals.org/cancerres/article/73/1/3/584147/Chloroquine-in-Cancer-Therapy-A-Double-Edged-Sword)
* [ study with TMZ] ( https://pubmed.ncbi.nlm.nih.gov/24991840/?dopt=Abstract)
|toxicity_explanation=
|toxicity_explanation=Chloroquine and Hydroxychloroquine are generally well-tolerated when used for glioblastoma treatment. Most studies observed minimal impact on the occurrence of adverse events. This implies that these drugs, especially Chloroquine, carry a low risk of causing harmful side effects or discomfort, therefore they are assigned the lowest toxicity level of 1.
}}

Accutane

2024-11-12T18:57:37Z

69.163.248.232:

{{TreatmentInfo
|drug_name=Isotretinoin (Accutane)
|FDA_approval=Yes (for acne treatment)
|used_for=Neuroblastoma, severe acne
|clinical_trial_phase=Used in various studies for cancer treatment
|common_side_effects=Dry skin, liver problems, increased blood lipid levels, dry mouth, muscle or joint pain, sun sensitivity
|OS_without=Not specified
|OS_with=Not specified
|PFS_without=Not specified
|PFS_with=Not specified
|usefulness_rating=3
|treatment_category=Repurposed Drugs
|toxicity_level=3
|book_text=Accutane (isotretinoin, 13-cis retinoic acid)

When Temodar has been combined with accutane, a retinoid used for acne treatment
(also known as 13-cis-retinoic acid, or isotretinoin), the PFS-6 (for recurrent tumors
improved from the 21% historical value of Temodar alone, to 32% (96).

In contrast to the improvement in clinical outcome when accutane was combined with
Temodar for recurrent tumors, a clinical trial with newly diagnosed patients that
combined Temodar with accutane produced less impressive results (97). Fifty-five
evaluable patients used both accutane and low-dosage Temodar during radiation,
followed by full-dose Temodar + accutane, and produced a median survival time of only
57 weeks and a two-year survival of 20%, both below the survival rates from the large
clinical trial with the same protocol that used Temodar without accutane. A second,
retrospective clinical trial in Canada (98) that combined accutane with Temodar with
newly diagnosed patients produced a median survival of 15.1 months and a two-year
survival of 26.7%, both comparable to when Temodar has been used alone.

Although accutane appears not to improve outcome when added to the standard Temodar
protocol, it does seem to have activity as a single agent. A phase II clinical trial

evaluating accutane for recurrent gliomas was conducted at the M. D. Anderson Brain
Tumor Center (99). The median survival time was 58 weeks for glioblastoma patients and
34 weeks for grade III gliomas. Aggregated over both tumor types (43 evaluable patients)
3 achieved a partial tumor regression, 7 had minor regressions, and 13 had tumor
stabilization. A more complete report, using accutane with 86 glioblastoma patients with
recurrent tumors was less impressive (100). Median survival time from the onset of
treatment was 25 weeks and PFS-6 was 19%. Accutane now is used at M. D. Anderson as
a "maintenance therapy" for patients after initial treatment with radiation or traditional
chemotherapy. It also has been used in Germany for patients who have had a complete
response to other treatment modalities as a maintenance therapy (101). The major side
effects have been dry skin, cracked lips, and headaches, although occasional liver toxicity
has also occurred. Increases in blood lipid levels frequently occur, often requiring anti-
cholesterol medication such as Lipitor. Accutane also may produce severe birth defects if
taken during pregnancy.

Although various data now suggest that accutane should not be combined with
chemotherapy (for example, see the discussion below in this chapter entitled A trial of 3
repurposed drugs plus Temodar), a series of studies with various types of cancer,
including pancreatic, ovarian, colorectal, and melanoma (although not yet with brain
tumors), suggest it can be very effective for patients who get a good response from their
initial treatment protocol. This is especially relevant to GBM patients who have clean
MRIs either after surgery or after treatment with radiation and chemotherapy. An
example of the protocol with ovarian cancer involved 65 patients who received the
standard treatment of a taxane and a platinum drug (316). After one year of the
standard treatment those receiving a benefit were moved to a maintenance treatment
using subcutaneous low-dose IL-2 plus oral 13 cRA at a dose of 0.5 mg/kg. This plan was
continued for one year after which frequency of dosing was gradually reduced. Patients
receiving this treatment plan had a median PFS of 23 months and a median survival of 53
months. Concomitantly, various measures of immune function (lymphocyte count, NK
cell count) were substantially improved and there was a substantial reduction in the level
of VEGF, reflecting a reduction in angiogenesis.

|notes=Isotretinoin, a retinoid related to vitamin A, controls cell growth by acting on specific nuclear receptors. It's used to treat severe acne and explored for cancer therapy potential, notably in neuroblastoma. It's important to avoid vitamin A supplements during treatment to prevent adverse interactions. Monitoring for liver function and blood lipid levels is advised due to possible side effects.
|links=[St. Jude’s comprehensive guide on isotretinoin](https://together.stjude.org/en-us/about-pediatric-cancer/treatment/medicines/isotretinoin.html)
|toxicity_explanation=Isotretinoin is rated as moderately toxic. While it has common side effects like dry skin and increased blood lipid levels, it has also been associated with severe side effects such as liver problems. This means that while taking Isotretinoin, frequent monitoring of health condition is required. Moreover, the use of this drug must be strictly monitored in pregnant women due to potential severe birth defects.
}}

[[Category:Treatments]]

Vitamin D

2024-11-12T18:57:26Z

69.163.248.232:

{{TreatmentInfo
|drug_name=Vitamin D
|FDA_approval=No
|used_for=Glioblastoma Multiforme (GBM), various types of cancer
|clinical_trial_phase=Various studies, including recent meta-analyses and reviews
|common_side_effects=Hypercalcemia at high doses of calcitriol; other forms generally safe
|OS_without=Not explicitly detailed in recent reviews
|OS_with=Recent meta-analyses suggest potential for improving cancer treatment outcomes
|PFS_without=Not specified
|PFS_with=Not specified
|usefulness_rating=4
|notes=Recent reviews underscore Vitamin D's potential in cancer prevention and treatment, emphasizing its impact on biological mechanisms related to cancer regulation and its possible synergistic effects with chemo/immunotherapeutic drugs. The dosage and supplementation strategies are critical for optimizing its therapeutic benefits.
|treatment_category=Hormones and Cancer Therapy
|links=
* [The impact of vitamin D on cancer: A mini review - PubMed](https://pubmed.ncbi.nlm.nih.gov/37054849/)
* [Vitamin D supplementation and total cancer incidence and mortality - British Journal of Cancer](https://www.nature.com/articles/s41416-020-01188-1)
|toxicity_level=2
|toxicity_explanation=A toxicity level of 2 for this treatment implies that it has a low toxicity level, meaning the common side effects observed are generally mild and tolerable. The main known side effect is a condition called Hypercalcemia, which is an excessive level of calcium in your blood, that occurs only at high doses of one type of Vitamin D variant. But, it's essential to follow recommended dosage and supplementation strategies for the best therapeutic benefits. The treatment lacks FDA approval currently, hence, it's important to have a conversation with your healthcare provider before starting any new supplement or treatment.
|book_text=Numerous laboratory studies have shown that Vitamin D is highly cytotoxic to cancer
cells, due to several different mechanisms (although labeled as a vitamin it more properly
should be considered a hormone). While most research has focused on its ability to
activate genes that cause cancer cells to differentiate into mature cells, other effects have
also been identified, including cell cycle regulation, inhibition of the insulin-like growth
factor, and the inhibition of angiogenesis (246). However, the calcitriol form of Vitamin
Dis not readily usable for cancer treatments because the dosages producing anti-cancer
effects also cause hypercalcemia, which can be life threatening (the major function of
Vitamin D is to regulate calcium absorption and resorption from the bones and teeth).
But like many vitamins/hormones, the generic designation refers not to a specific
chemical structure but to a family of related molecules that may have different properties
of various sorts. For Vitamin D several of these variants (commonly referred to as
analogues) have been shown to effectively inhibit cancer cell growth but without the
same degree of toxic hypercalcemia. In a 2002 paper in the Journal of Neuro-oncology
(247), 10 patients with glioblastoma and one with a grade III AA tumor received a form
of Vitamin D called alfacalcidol in a dosage of .o4 micrograms/kg each day, a dosage
that produced no significant hypercalcemia. The median survival was 21 months, and
three of the eleven were long-term survivors (greater than 5 years). Although the
percentage of patients who responded to the treatment was not high, the fact that any
relatively non-toxic treatment can produce any number of long-term survivors is
remarkable. There is also strong reason to believe that Vitamin D is synergistic with
retinoids such as accutane (248). Its effectiveness is also increased in the presence of
dexamethasone (249) and a variety of anti-oxidants, notably carnosic acid, but also
lycopene, curcumin, silibinin, and selenium (250).

Alfacalcidol is not available in the USA, but is available in Europe and Canada. For those
in the USA it is possible obtain it from various online marketers. It also should be noted
that several other Vitamin D analogues are available, which also have much reduced
hypercalcemic effects. One of these, paricalcitol, was developed for treatment of a
disorder of the parathyroid gland, and recently has been the subject of several
experimental studies (251, 252, 253) that have shown it to be highly cytotoxic to
34

many different types of cancer. Given that other forms of Vitamin D have been shown to
be highly cytotoxic to for glioblastoma cells, and that glioma cells are known to have
receptors for Vitamin D, it seems likely that paricalcitol should have efficacy for
glioblastoma as well. Unfortunately, its routine use is complicated by the fact it is
available only in a form that requires intravenous injection.

The most common version of Vitamin D3 found in health food stores is cholecalciferol,
which is the precursor of calcitriol, the form of Vitamin D utilized by the body. A recent
study of cholecalciferol with prostate cancer patients who had progressed after standard
therapy (254) suggests that this common form of Vitamin D3 may be clinically
beneficial. Fifteen patients who had failed standard treatments were given 2000 I.U.
daily. PSA levels were reduced or stayed the same for nine patients, and there was a
reliable decrease in the rate of PSA increase for the remainder. No side effects of the
treatment were reported by any of the patients.

Because serum Vitamin D levels have recently been shown to be inversely related to
cancer incidence, there recently has been considerable discussion about the dosage that is
toxic. Doses as high as 5000-10,000 I.U. per day appear to be safe. Recently, it has
become common for women suffering from osteoporosis with low Vitamin D levels to be
given as much as 50,000, I.U./day for short time periods. Nevertheless, it is important to
note that all forms of Vitamin D can occasionally produce dangerous serum calcium
levels, in part because there is a great deal of variability in their effects across individuals.
It is thus important that blood calcium levels be monitored, especially while a nontoxic
dosage is being established.
}}

Melatonin

2024-11-12T18:57:14Z

69.163.248.232:

{{TreatmentInfo
|drug_name=Melatonin
|FDA_approval=No
|used_for=Jet lag, insomnia, various types of cancer including Glioblastoma Multiforme (GBM)
|clinical_trial_phase=Phase-2 and Phase-3 trials
|clinical_trial_explanation=Melatonin has been part of numerous clinical trials, particularly in Italy, often in combination with chemotherapy or immunotherapy. The outcomes have shown potential benefits including increased survival rates and tumor regression:

* In a study with 30 GBM patients, those treated with melatonin in addition to radiation therapy showed significantly higher survival rates compared to those receiving only radiation.
* Larger trials involving various types of advanced metastatic cancers have reported that melatonin enhanced the efficacy of chemotherapy, leading to higher rates of tumor regression and increased survival.
* Despite these positive findings, the studies often involved small sample sizes or patients in terminal stages, which might influence broader clinical acceptance.
|common_side_effects=No known toxic side effects
|OS_without=1 out of 16 patients was alive after one year.
|OS_with= 6 out of 14 patients were alive after one year
|PFS_without=Not specified
|PFS_with=Not specified
|usefulness_rating=4
|notes=Melatonin is a hormone that regulates the body's diurnal rhythm and is used for the treatment of sleep disorders. In cancer treatment, it's hypothesized to boost the immune system, inhibit angiogenesis, and have direct cytotoxic effects on certain cancer cells. Clinical research, primarily in Italy, has explored its use alone or in combination with chemotherapy or immunotherapy, showing potential for increasing survival rates and reducing chemotherapy toxicity.

Patients considering melatonin for GBM should consult with their oncologist. It’s essential to discuss the potential benefits and risks, considering that the most compelling evidence supports its use alongside chemotherapy. There might also be concerns about interactions with other medications and the appropriate dosage for anti-cancer effects, typically higher than those used for sleep disorders.

== GBM Study ==
* '''Trial''': Randomly assigned 30 GBM patients to radiation alone or radiation with 20 mg/day of melatonin.
* '''Survival''':
** With Melatonin: 6 out of 14 patients were alive after one year.
** Without Melatonin: 1 out of 16 patients was alive after one year.
* '''Reference''': [Melatonin in the Treatment of Cancer (PDF)](https://www.acesototalhealth.com/wp-content/uploads/2020/07/Melatonin-in-the-tx-of-cancer.pdf).

== Larger Trials (Advanced Metastatic Cancer) ==
* '''Trial''': 250 patients with advanced metastatic cancer of various types were randomized to chemotherapy alone or chemotherapy plus 20 mg of melatonin per day.
* '''Tumor Regression''':
** With Melatonin: 42 out of 124 patients had tumor regression (including 6 complete regressions).
** Without Melatonin: 19 out of 126 patients had tumor regression (with zero complete regressions).
* '''Survival''':
** With Melatonin: 63 out of 124 patients were alive after one year.
** Without Melatonin: 29 out of 126 patients were alive after one year.
* '''Reference''': [Melatonin in Cancer Management: Progress and Promise](https://aacrjournals.org/cancerres/article/79/18/4827/636539/Melatonin-in-Cancer-Management-Progress-and-Promise).

== Metastatic Non-Small-Cell Lung Cancer Study ==
* '''Trial''': 100 patients with metastatic non-small-cell lung cancer compared chemotherapy alone versus chemotherapy with melatonin.
* '''Tumor Regression''':
** With Melatonin: 17 out of 49 patients had either complete (2) or partial (15) regression.
** Without Melatonin: 9 out of 51 patients had a partial tumor regression.
* '''Survival''':
** With Melatonin: 40% of patients survived for one year and 30% for two years.
** Without Melatonin: 20% of patients survived for one year and 0% for two years.
* '''Reference''': [Memorial Sloan Kettering Cancer Center](https://www.mskcc.org/cancer-care/integrative-medicine/herbs/melatonin) and [Melatonin Research](https://www.melatonin-research.net/index.php/MR/article/view/45).

== Aggregate Study (Lung, Colorectal, and Gastric Cancer) ==
* '''Patients''': 370 patients with lung cancer, colorectal cancer, and gastric cancer.
* '''Response Rate''':
** With Melatonin: 36% response rate (tumor regression).
** Without Melatonin: 20% response rate.
* '''Survival''':
** With Melatonin: 25% two-year survival rate.
** Without Melatonin: 13% two-year survival rate.

== Ongoing Research ==
* '''Research''': Mayo Clinic is investigating the use of melatonin to enhance glioblastoma treatment with temozolomide.
* '''Reference''': [Mayo Clinic](https://www.mayo.edu/research/labs/brain-tumor-stem-cell-research/research/melatonin-enhance-cancer-treatments).

|usefulness_explanation=
* '''Immune System Enhancement''': Augmentation of T-helper cell activity, crucial for targeting cancer cells.
* '''Inhibition of Angiogenesis''': Reduction in blood vessel formation essential for tumor growth.
* '''Direct Cytotoxic Effects''': Induction of apoptosis in cancer cells, including glioblastoma.
* '''Reduction of Chemotherapy Toxicity''': Mitigation of chemotherapy side effects, improving tolerability and adherence to treatment schedules.
* '''Modulation of Tumor Metabolism''': Affects energy production pathways in cancer cells, making them more susceptible to treatments.

|treatment_category=Hormones and Cancer Therapy
|links=https://www.mdpi.com/2073-4409/11/21/3467
https://www.mdpi.com/2073-4409/9/3/599
https://academic.oup.com/noa/article/3/Supplement_1/i13/6186371?login=false
https://www.mayo.edu/research/labs/brain-tumor-stem-cell-research/research/melatonin-enhance-cancer-treatments
|toxicity_level=1
|toxicity_explanation=Melatonin is considered to have a low toxicity level, with no known toxic side effects. It is generally regarded as safe for use in the dosages typically administered for both sleep disorders and experimental cancer treatment protocols.
|mechanism=Immune System Enhancement: Melatonin is believed to augment the activity of T-helper cells, which play a significant role in orchestrating the immune response against cancer cells.

Inhibition of Angiogenesis: Melatonin has been shown to inhibit the formation of new blood vessels (angiogenesis) necessary for tumor growth.

Direct Cytotoxic Effects: Some studies suggest that melatonin may directly kill cancer cells, as observed in melanoma cells.

Reduction of Chemotherapy Toxicity: Clinical trials have indicated that melatonin can reduce the side effects of chemotherapy, especially in blood counts, making it a potential adjuvant in cancer treatment.
|book_text=This is a naturally occurring hormone secreted by the pineal gland that regulates the
body's diurnal rhythm. It is commonly used for the treatment of jet lag and for insomnia.
It is readily available in any health food store and most drug stores. Its role in cancer
treatment has been based on the assumption that it boosts the immune system, with the
current hypothesis being that it augments the activity of T-helper cells. It recently also
has been shown to inhibit angiogenesis (225). It may also have direct cytotoxic effects on
some types of cancer cells, notably melanoma cells. It has no known toxic side effects.

Clinical research on the use of melatonin for cancer treatment has been done primarily in
Italy, where it has been used either as a single agent after radiation treatments, or in
combination with various chemotherapy or immunotherapy regimens, most frequently
interleukin-2. Part of the rationale for such combinations is that it decreases the side
effects of the chemotherapy, especially with respect to blood counts. One of the clinical
32

studies (226) randomly assigned 30 GBM patients either to radiation alone (n=16) or to
radiation concomitant with 20 mg/day of melatonin (n=14). Melatonin was continued
after completion of the radiation. Survival was significantly greater for subjects receiving
the melatonin. In terms of one-year survival rates, 6/14 patients receiving melatonin were
alive, while only 1/16 patients without melatonin was alive.

This GBM study involved a relatively small number of patients, so that the effects
should be considered tentative until a larger study is conducted. However, comparable
effects have been reported in a similar design for the use of melatonin with advanced
lung cancer (227). Like the GBM study, a substantial increase in survival rate occurred
for the patients receiving melatonin.

To date there have been at least a dozen phase-2 clinical trials using melatonin either
alone or in combination with other agents and five phase-3 trials involving random
assignment of subjects to melatonin versus some type of control group. The majority of
these has been relatively small and has involved patients in the terminal stages of their
disease, which is perhaps why American oncologists have largely ignored them.

However, some trials have been much larger and seem to leave little doubt that melatonin
significantly increases the efficacy of chemotherapy. One of the most extensive
randomized clinical trials involved 250 patients with advanced metastatic cancer of
various types (228). Patients were randomly assigned to chemotherapy alone (using
different chemotherapies for different types of cancer) or chemotherapy plus 20 mg of
melatonin per day. Objective tumor regression occurred in 42 (including 6 complete
regressions) of 124 patients receiving melatonin but in only 19/126 (with zero complete
regressions) of the control patients. A comparable difference occurred for survival rate:
63/124 of those receiving melatonin were alive after one year while only 29/126 were
alive of those receiving chemotherapy alone. A different trial, involving 100 patients with
metastatic non small-cell lung cancer (229), compared chemotherapy alone with
chemotherapy in combination with melatonin. With chemotherapy alone, 9 of 51 patients
had a partial tumor regression, while 17 of 49 chemo + melatonin patients had either a
complete (n=2) or partial (n=15) regression. Twenty percent of the chemo-alone patients
survived for one year and zero for two years, while the corresponding numbers for chemo
+ melatonin were 40% and 30%. Melatonin not only increased the efficacy of
chemotherapy, but also significantly reduced its toxicity.

The most extensive report included 370 patients, subdivided into three different types of
cancer: lung cancer (non-small cell), colorectal cancer, and gastric cancer (230).
Aggregated over all three types, the response rate (percentage of patients with tumor
regression) was 36% for those treated with chemotherapy and melatonin, versus 20% for
those treated with chemotherapy alone. The corresponding two-year survival rates were
25% vs. 13%. Melatonin’s benefits occurred for all three cancer types that were included.
Moreover, patients receiving melatonin had fewer side effects.
33

These trials leave little doubt that the effects of melatonin are of clinical significance.
Moreover, a recent study has shown that using multiple components of the pineal gland
secretions instead of melatonin alone enhances clinical effectiveness still further (231).
One caveat about the use of melatonin is that a recent randomized trial compared
radiation treatment for metastatic brain cancer with and without melatonin and found no
benefit of the melatonin (232). Given that almost all of the supporting evidence for the
use of melatonin has come from its addition to chemotherapy, it is possible that it offers
no benefit when added to radiation, perhaps because of its strong antioxidant properties.
}}

Parthenolide

2024-11-12T18:50:19Z

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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.
}}

Metformin

2024-11-12T18:49:53Z

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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.
}}

Sulforaphane

2024-11-12T18:49:27Z

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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.
}}

Resveratrol

2024-11-12T18:49:00Z

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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.
}}

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

2024-11-12T18:48:33Z

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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.
}}

Herpes Virus

2024-11-12T18:47:40Z

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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).
}}

Newcastle Disease Virus

2024-11-12T18:47:14Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{TreatmentInfo
|drug_name=Newcastle Disease Virus
|treatment_category=Oncolytic virotherapy
|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.
}}

DNX-2401 adenovirus

2024-11-12T18:46:48Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{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.
}}

Genetically modified Poliovirus (PVS-RIPO)

2024-11-12T18:46:21Z

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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.
}}

Rindopepimut (CDX-110)

2024-11-12T18:45:29Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{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=Tumor-associated antigen vaccines
}}

Anti-CMV Dendritic Cell Vaccine

2024-11-12T18:45:02Z

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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.
|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).
|treatment_category=Tumor-associated antigen vaccines

}}

SL-701

2024-11-12T18:44:36Z

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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.
|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
|treatment_category=Tumor-associated antigen vaccines

}}

ICT-107

2024-11-12T18:44:10Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{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
}}

Dendritic Cell Vaccine (DCVax-L)

2024-11-12T18:43:18Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{TreatmentInfo
|drug_name=Dendritic Cell Vaccine (DCVax-L)
|treatment_category=Specialized Treatments
|treatment_category=Clinical Trials
|treatment_category=Right to Try
|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
}}

CPT-11 (Irinotecan)

2024-11-12T18:42:52Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{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
}}

Carboplatin

2024-11-12T18:42:26Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{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
}}

Fotemustine

2024-11-12T18:42:00Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{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
}}

BCNU (Carmustine)

2024-11-12T18:41:33Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{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
}}

VAL-083 (Dianhydrogalactitol)

2024-11-12T18:41:07Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{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
}}

Optune

2024-11-12T18:38:58Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{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
}}

Chloroquine and Hydroxychloroquine

2024-11-12T18:38:06Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{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.
}}

Silibinin (an ingredient in Milk Thistle)

2024-11-12T18:37:40Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{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.
}}

MN-166

2024-11-12T18:37:13Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{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.
}}

Letrozole

2024-11-12T18:36:47Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{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.
}}

VT-122

2024-11-12T18:36:21Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{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
}}

Angiotensin-II Receptor Blockers (ARB)

2024-11-12T18:35:55Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{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
|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.
}}

Gleevec (Imatinib)

2024-11-12T18:35:28Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{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%.
}}

Bevacizumab (Avastin)

2024-11-12T18:35:02Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{TreatmentInfo
|drug_name=Bevacizumab (Avastin)
|FDA_approval=Yes, for recurrent glioblastoma
|used_for=Glioblastoma
|clinical_trial_phase=Phase III
|common_side_effects=Hypertension, proteinuria, and hemorrhage
|OS_with=AVAglio trial: 16.8 months; RTOG trial: 15.7 months
|usefulness_rating=4
|notes=Avastin improves PFS when used initially, but no significant benefit for overall survival compared to Avastin given at recurrence.
|treatment_category=Other Chemotherapy and Cancer Drugs
|toxicity_level=3
|toxicity_explanation=Bevacizumab has an intermediate level of toxicity. Although it is a powerful medication against glioblastoma, it can have serious side effects including high blood pressure (hypertension), presence of excess proteins in the urine (proteinuria), and bleeding (hemorrhage). These side effects can impact your general health and daily activities. Therefore, this treatment needs regular monitoring by your health care provider and should be used with caution.
|book_text=The most notable development in drug combinations has been the addition of the anti-
angiogenic drug, Avastin (also known as bevacizumab), to the standard Stupp protocol.
As will be discussed later, Avastin has FDA approval for the treatment of glioblastomas
that have recurred or progressed after initial treatment. Several clinical trials have now
investigated its combination with the gold standard Temodar protocol.

Recently, there have been two large randomized phase III clinical trials comparing

the Stupp protocol and the Stupp protocol + Avastin, for newly diagnosed patients. In the
first of these (70), known as the AVAglio trial, median PFS was 10.6 months for those
receiving Avastin versus 6.2 months for those receiving only the Stupp protocol, a
statistically significant difference. However, median overall survival was not different
(16.8 months vs. 16.7 months). It should be noted that patients in the control group

typically received Avastin after tumor progression occurred, so that the comparison was

really between Avastin given early versus Avastin given only after recurrence. Additional
results were that 72% of the Avastin group was alive at one year, compared to 66% of the
control group, while two year survival was 34% vs. 30%.

In the second of these large trials (71), conducted by the RTOG consortium, the design
was essentially similar to the AVAglio trial, as were the results. Median PFS was 10
months for those receiving Avastin vs. 7.3 months for the control group (again statistically
significant), while median overall survival was 15.7 months for the Avastin group
compared to 16.1 months for the control, a nonsignificant difference.

The best interpretation of these results is that patients have a longer time without tumor
progression, and presumably a better quality of life, when Avastin is used as part of the
initial treatment. However, there is no benefit for overall survival, when compared to
withholding Avastin until recurrence is detected. An additional feature of the results, not
emphasized by the authors of the reports, is that the overall survival times were not
notably better, and in many cases worse, than those obtained when the Stupp protocol is
combined with various other treatment agents.
}}

Procarbazine

2024-11-12T18:34:35Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{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.
}}

Platinum Compounds

2024-11-12T18:34:08Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{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.
}}

BCNU (Carmustine) and Gliadel (Carmustine Wafers)

2024-11-12T18:33:42Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{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
}}

CCNU (Lomustine)

2024-11-12T18:33:15Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{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=Other Chemotherapy and Cancer Drugs
|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.
}}

MDNA55

2024-11-12T18:32:49Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{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.
}}

ABT-414

2024-11-12T18:32:23Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{TreatmentInfo
|drug_name=ABT-414
|FDA_approval=No
|used_for=Targeting EGFR overexpressing glioblastoma cells
|clinical_trial_phase=Phase 1
|common_side_effects=Eye toxicities, especially blurred vision
|OS_with=Not reached at a median follow-up of 5.8 months
|PFS_with=6.1 months for all patients, 5.9 months for EGFR amplified patients
|usefulness_rating=2
|notes=ABT-414, an antibody-drug conjugate, selectively targets EGFR expressing tumor cells with minimal effects on healthy tissue. The phase 1 study highlighted challenges such as variable doses, study drug discontinuations due to toxicities, and small sample size, advising caution in evaluating efficacy parameters.
|treatment_category=Antibody-Drug Conjugates and other protein-drug conjugates
|links=
|toxicity_level=4
|toxicity_explanation=The drug ABT-414 is in phase 1 of its clinical trials. It demonstrates a tendency towards eye toxicities, especially causing blurred vision. This is an indication of potentially high toxicity. However, due to small sample size and other variables in the study, the evaluations should be taken with caution. It is advised to expect a higher level of toxicity until tested further in next clinical trial phases.
}}

Celebrex

2024-11-12T18:31:56Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{TreatmentInfo
|drug_name=Celebrex (Celecoxib) and Other NSAIDs
|FDA_approval=Yes (Celebrex is FDA-approved for arthritis and pain, but not specifically for cancer treatment)
|used_for=Investigational use in cancer treatment due to anti-inflammatory, anti-angiogenic, and potential tumor growth inhibition properties
|clinical_trial_phase=Early clinical trials and observational studies, including phase 2 trials combining Celebrex with conventional cancer treatments
|common_side_effects=Generally well-tolerated; potential gastrointestinal issues with long-term use of some NSAIDs. Celebrex designed to minimize COX-1 inhibition and related stomach issues.
|OS_with=Not specifically documented; clinical trials have shown mixed results, with some indicating significant benefit when added to standard chemotherapy protocols
|PFS_with=Variable across studies; for example, a study combining Temodar with Celebrex showed a PFS-6 of 35%, another combining Celebrex with CPT-11 showed PFS-6 of 25%
|usefulness_rating=3
|notes=The use of Celebrex and other NSAIDs in cancer treatment is based on their anti-inflammatory properties, inhibition of COX-2 enzymes, and subsequent reduction in angiogenesis and tumor growth. While preclinical and early clinical research indicates potential benefits, including immune system enhancement and apoptosis induction, results from clinical trials have been mixed. The mechanisms underlying NSAIDs' anti-cancer effects, particularly in gliomas, suggest a promising avenue for research, emphasizing the need for further large-scale, randomized clinical trials to better understand their efficacy and optimal integration into cancer therapy regimens.
|treatment_category=Repurposed Drugs
|toxicity_level=2.5
|book_text=Celebrex (and other NSAIDs)

Carcinogenesis of several types involves an inflammatory process. When anti-
inflammatory drugs such as aspirin or ibuprofen are taken on a regular basis the
incidence of colon cancer is reduced as much as 50%. This substantial effectiveness has
motivated investigation of the mechanisms of these benefits. One component of the
inflammatory process is angiogenesis, which is now believed to be a critical component of
cancer growth. COX-2 enzymes play an important role in inflammation, so that COX-2
inhibitors should reduce angiogenesis and inhibit tumor growth. Many nonsteroidal anti-
inflammatory drugs (NSAIDs) are known to be COX-2 inhibitors, but most (e.g.,
ibuprofen) also inhibit COX-1 enzymes, which are necessary for healthy maintenance of
the stomach lining, which is why many users of NSAIDs eventually develop intolerance
to them. Thus, much recent attention has been given to the new COX-2 inhibitors such as
Celebrex that were developed to avoid COX-1 inhibition for the purposes of arthritis
treatment. Because inhibition of angiogenesis is one of the major new approaches to the
treatment of cancer, some oncologists have begun adding Celebrex to their regular
treatment protocols, based on laboratory findings that COX-2 inhibitors inhibit tumor
growth. In recent meetings of American Society for Clinical Oncology (ASCO), there

have been various clinical trials reported that combined one or another COX-2 inhibitor
with conventional radiation, chemotherapy, and new targeted treatments. The great
majority of these were phase 2 clinical trials which had only historical controls with the
conventional treatment alone to assess the value of the added COX-2 inhibitors, but most
concluded there appeared to be a significant benefit, Some larger randomized clinical
trials (115, 116) have shown substantial outcome improvements when celebrex has been
added to standard chemotherapy protocols, but others have failed to find a benefit.

Two clinical trials have been reported that have used celebrex in the treatment of gliomas
In a clinical trial conducted jointly by several hospitals in New York, Temodar was
combined with celebrex (117). For the 46 patients in the study (37 with GBM), the PFS-6
was 35%. However, an unusual schedule of Temodar was also used, so whether the results
were due to the new schedule or the celebrex is uncertain. Celebrex has also been
combined with CPT-11 (118), a chemotherapy agent used widely for colon cancer, with
�patients with recurrent tumors, and produced a PFS-6 value of 25%.

Because of the mild toxicity of NSAIDS, considerable recent research has investigated
the mechanisms of their clinical benefit. Whereas initial research focused on the anti-
angiogenic properties of this class of drugs, several other mechanisms have been
identified, including the enhancement of various aspects of the immune system, and
inhibition of the genes that prevent damaged cells from undergoing apoptosis (119). It is
critical to note that many of the mechanisms by which NSAIDS work are strongly
involved in the growth of high-grade gliomas, and that the expression of the
cyclooxygenase enzyme that is the target of COX-2 inhibitors correlates strongly with the
proliferation rate of glioblastoma tumors and correlates inversely with survival time (120,
121).

|links=
|toxicity_explanation=The toxicity level of 2.5 indicates that Celecoxib (Celebrex) and other NSAIDs have a moderate level of side effects, which are mostly related to potential stomach issues with long-term use. However, Celebrex has been designed to minimize these issues. Even though their use in cancer treatment is experimental, these drugs are generally well-tolerated. A toxicity level of 5 would represent a treatment with severe and frequent side effects.
}}

Thyroid Hormone T4 (Thyroxine) Suppression

2024-11-12T18:31:30Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{TreatmentInfo
|drug_name=Thyroid Hormone T4 (Thyroxine) Suppression
|FDA_approval=No (Used off-label for cancer treatment; specific regimen for cancer not FDA-approved)
|used_for=Investigational use in cancer treatment, particularly in glioblastoma, based on observations of improved outcomes with hypothyroid status
|clinical_trial_phase=Early clinical trials and case studies, including a phase 2 clinical trial in Israel (NCT02654041)
|common_side_effects=Carefully monitored to avoid clinical symptoms of hypothyroidism; includes potential for fatigue if not properly managed
|OS_with=In early studies, hypothyroid patients showed median survival of 10.1 months compared to 3.1 months in non-hypothyroid patients. Remarkable long-term survivors in informal cohort studies with advanced cancer, including glioblastoma patients surviving 36 and 48 months.
|PFS_with=Not specifically documented; focus on overall survival improvements
|usefulness_rating=3
|notes=Thyroid Hormone T4 Suppression Therapy involves inducing chemical hypothyroidism via propylthiouracil or suppressing T4 levels with methimazole and supplementing with synthetic T3 (Cytomel) to mitigate cancer-promoting effects of thyroid hormones while avoiding hypothyroidism symptoms. Discovery of thyroid hormone receptors on cancer cells provides a mechanism for their potential cancer-promoting effects. Early studies and case reports suggest potential benefits in cancer treatment, especially glioblastoma, with notable long-term survival in some patients. Further research, including ongoing clinical trials, is needed to validate these findings and optimize treatment protocols.
|treatment_category=Hormones and Cancer Therapy
|links=NCT02654041
|toxicity_level=2
|toxicity_explanation=The toxicity level of Thyroid Hormone T4 Suppression Therapy is rated as a 2, which indicates a low level of toxicity. This is because the therapy is designed to suppress the hormone levels in the body and replace them with a synthetic version to help fight cancer cells. The side effects, such as fatigue, are typically manageable, especially when the treatment is carefully monitored. Nonetheless, this therapy is not without potential side effects and it is applied off-label, hence it's necessary to discuss with your healthcare provider.
|book_text=Based on observations of the relationship between hypothyroid status (depressed thyroid
function) and improved outcomes in cancer patients dating at least back to 1988, Aleck
Hercbergs and colleagues at the Cleveland Clinic conducted a clinical trial, published in
2003, in which 22 high grade glioma patients were treated with propylthiouracil to induce
chemical hypothyroidism, and high dose tamoxifen (349). 15 of the patients had the
diagnosis of glioblastoma and the remainder were grade 3 gliomas. Half of the patients
(11 of 22) attained hypothyroid status, although no clinical symptoms of hypothyroidism
were observed. A survival analysis determined that median survival in the 11 hypothyroid
patients was 10.1 months, while median survival in the non-hypothyroid group was only
3.1months. After adjusting for the younger age of the hypothyroid patients, survival was
still longer in the hypothyroid group, with borderline statistical significance (p=0.08).

Later, in 2005, the discovery of cell surface receptors for thyroid hormones on avB3
(alphaVbeta3) integrins, provided a mechanism for their cancer-promoting effects (350).
This particular integrin tends to be overexpressed on cancer cells, and stimulation of this
integrin by thyroid hormones leads to increased angiogenesis, tumor cell proliferation,
and resistance to apoptosis (351).

Following publication of the 2003 trial, many cancer physicians and cancer patients
reached out to Hercbergs, resulting in a cohort of 23 advanced cancer patients treated
informally with thyroid suppression therapy in addition to standard treatments (351).
Patients who were taking synthetic T4 for pre-existing hypothyroidism were abruptly
switched to synthetic T3 (Cytomel) and in three of these patients there was a rapid and
durable tumor remission observed in conjuction with standard treatments. In the
remaining patients, methimazole was used to depress T4 levels to below the reference
range, and patients again received synthetic T3 hormone (Cytomel). The rationale for this
31

is that even though T3 is the active form of thyroid hormone, the affinity for T4 at the
thyroid hormone receptor on the integrin is greater than for T3, and T4 is a stronger
inducer of cancer cell proliferation. The suppression of T4 and supplementation with T3
(Cytomel) is therefore thought to reduce the major cancer-promoting effect of thyroid
hormones while avoiding the clinical symptoms of hypothyroidism, such as fatigue.

Four patients with glioblastoma were included in this study, including a 67 year old male
with a KPS of 70 and a partial resection who survived 36 months (3 years), and a 64 year
old male with a KPS of 60 who had undergone a biopsy only and lived for 48 months (4
years). Both of these patients had an expected survival of 10 months. A third female
glioblastoma patient, aged 68, had a low KPS of 40 and survived for 8 months.

Several patients were excluded from the study who had either failed to achieve free T4
depletion, or who voluntary discontinued treatment (perhaps due to a perception of lack
of benefit or an actual lack of benefit). Therefore the 100% response rate observed in this
study is perhaps an exaggeration, although the long survival of two out of four advanced
GBM patients certainly suggests an effect of the treatment, as standard treatments alone
rarely lead to such positive outcomes. Additionally, Hercbergs et al. published a case
report of a 64 year old patient with optic pathway glioma, progressive after standard
treatments, who responded to T4 depletion with propylthiouracil followed by carboplatin
chemotherapy with a remission period of 2.5 years and overall survival of 4.5 years (352).

A phase 2 clinical trial testing T4 suppression with methimazole and Cytomel (synthetic
T3) in addition to standard treatment for newly diagnosed glioblastoma has started
recruiting in Tel-Aviv, Israel early in 2016 (NCT02654041).
}}

Garlic

2024-11-12T18:31:04Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{TreatmentInfo
|drug_name=Garlic (Allium sativum)
|FDA_approval=No (Utilized as a dietary supplement; not FDA-approved for cancer treatment)
|used_for=Investigational use in oncology, focusing on its cytotoxic effects against cancer cells and HDAC inhibition
|clinical_trial_phase=Mostly preclinical, involving cell culture studies and some early-stage human research
|common_side_effects=Generally well-tolerated; known side effects include gastrointestinal discomfort and a strong odor. Rare cases of allergic reactions.
|OS_with=Not applicable; the majority of evidence is from preclinical studies, without detailed human data on overall survival impacts.
|PFS_with=Not applicable; current research has not progressed to detailed assessments of progression-free survival in cancer patients.
|usefulness_rating=3
|notes=Garlic, recognized for centuries for its medicinal properties, has shown promise in preclinical studies for its potential anti-cancer effects. These include inducing apoptosis in glioblastoma cell lines and acting as a potent HDAC inhibitor. While these mechanisms suggest garlic could play a role in cancer prevention and possibly treatment, comprehensive clinical trials are needed to substantiate its efficacy and determine its therapeutic utility in oncology.
|treatment_category=Nutraceuticals
|links=
|toxicity_level=1
|toxicity_explanation=Garlic is used as a dietary supplement and is generally well-tolerated by most people. The most common side effects reported include gastrointestinal discomfort and a strong odor. There is currently not enough research to suggest that garlic as a treatment for glioblastoma has severe toxic side effects. So, it has a low toxicity level of 1.
}}

Fish oil

2024-11-12T18:30:36Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{TreatmentInfo
|drug_name=Fish Oil (Omega-3 Fatty Acids: EPA and DHA)
|FDA_approval=No (Used as a dietary supplement; not specifically FDA-approved for cancer treatment)
|used_for=Investigational use in cancer treatment for potential cytotoxic effects and enhancement of chemotherapy and radiation therapy efficacy
|clinical_trial_phase=Clinical trials (e.g., advanced cancer study with cachexia, metastatic breast cancer Phase II trial, advanced non-small cell lung cancer trial)
|common_side_effects=Well-tolerated; potential side effects include fishy aftertaste, gastrointestinal discomfort
|OS_without=Malnourished advanced cancer patients: 110 days; adequately nourished patients: 350 days; chemotherapy alone in non-small cell lung cancer: 39% one-year survival
|OS_with=Fish oil supplementation: Malnourished advanced cancer patients: 210 days; adequately nourished patients: 500 days; metastatic breast cancer trial with high-DHA: median survival of 34 months vs. low-DHA: 18 months; non-small cell lung cancer with fish oil: 60% one-year survival
|PFS_with=Not specifically documented; research highlights increased survival and potential for enhanced treatment efficacy
|usefulness_rating=4
|notes=Omega-3 fatty acids, EPA and DHA, from fish oil have shown anti-cancer properties in both lab and clinical settings, including apoptosis induction and chemotherapy/radiation enhancement. Clinical trials indicate fish oil increases survival times and reduces chemotherapy toxicity in patients with advanced cancers, suggesting a beneficial role in cancer therapy. The data underscore the need for additional research to establish efficacy, optimal dosing, and integration into conventional cancer treatment protocols.
|treatment_category=Nutraceuticals
|toxicity_level=1
|book_text=Fish oil (source of omega-3 fatty acids)

The major omega-3 fatty acids found in cold-water fish oil, eicosapentaenoic acid (EPA)
and docosahexaenoic acid (DHA), have also been demonstrated to have potent cytotoxic
effects on cancer cells in various laboratory experiments. Part of their mechanism of
action is similar to that of GLA, in that the metabolism of these fatty acids creates high
levels of free radicals. In addition, a recent laboratory study has shown that EPA-treated
tumors showed a significant arrest of cell division due to inhibition of cyclins at the G1
phase of cell division, which resulted in an increased rate of programmed cell death
known as apoptosis (241).

A clinical trial comparing fish-oil supplements versus a placebo has also been reported,
involving patients with several different types of advanced cancer (242). Thirty
malnourished patients suffering from cachexia were randomly assigned to receive 18 g of
fish oil per day or a placebo sugar pill. An additional thirty subjects, adequately
nourished, received a similar random assignment. For both groups the fish oil
significantly increased survival. For the malnourished patients the median survival times,
as estimated from their survivor functions, were 110 days for the patients receiving
placebo and 210 days for patients in the fish oil group. For the adequately nourished
patients, the corresponding numbers were 350 versus 500 days.

In laboratory studies (243) fish oil has also been shown to increase the effectiveness of
chemotherapy and radiation. A phase II trial involving 25 heavily pretreated metastatic
breast cancer patients, used 1.8 g/day of DHA, one of the two major fatty acids in fish oil,
in combination with standard anthracycline-based chemotherapy (244). Patients
previously had failed both chemotherapy and hormone treatments and many had
multiple metastases, including many liver metastases. Because this was a phase II trial,
there was no control group that received chemotherapy alone, but patients were
subdivided according to their level of plasma DHA. The two groups were approximately
equal with respect to all major prognostic variables. Median survival for the high DHA
patients was 34 months, vs. 18 months for the low-DHA patients.

A second clinical trial presented 2200 mg of EPA plus 240 mg of DHA to patients with
advanced non small cell lung cancer (245). Patients either received only the standard of
care of chemotherapy, or the same treatment in combination with daily fish oil. Response
rate (tumor regressions) was 60% in the fish oil group and 26% in those receiving only
the standard of care. One-year survival was 60% in the fish oil group versus 39% in those
receiving only chemotherapy. Chemotherapy toxicity was also decreased in those using
fish oil.

|links=
|toxicity_explanation=Fish Oil, or Omega-3 Fatty Acids (EPA and DHA), is well-tolerated by patients. This supplement is not typically associated with severe or dangerous side effects. The most common side effects include a fishy aftertaste and minor gastrointestinal discomfort. Therefore, it's toxicity level is low.
}}

Ellagic acid

2024-11-12T18:30:10Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{TreatmentInfo
|drug_name=Ellagic Acid
|FDA_approval=No (Utilized as a dietary component; not FDA-approved for cancer treatment)
|used_for=Investigational use in cancer prevention and treatment; noted for potential anti-cancer properties in laboratory studies
|clinical_trial_phase=Preclinical and early clinical trials (e.g., prostate cancer study at UCLA)
|common_side_effects=Not specifically documented; as a naturally occurring compound in fruits and nuts, it is generally considered safe
|OS_with=Not applicable; current research focuses on biochemical effects and prevention metrics like PSA doubling time in prostate cancer
|PFS_with=Not applicable; direct impacts on progression-free survival in cancer patients are not yet established
|usefulness_rating=3
|notes=Ellagic Acid, found in various fruits and nuts, exhibits anti-cancer properties in laboratory experiments, including the inhibition of cell division and induction of apoptosis. Although clinical trials specific to brain cancer are lacking, a study with prostate cancer patients demonstrated that pomegranate juice, rich in ellagitannins (ellagic acid precursors), significantly slowed the increase in PSA levels, suggesting a potential for cancer management. These findings indicate ellagic acid's promise in cancer prevention and warrant further clinical investigation to confirm its efficacy and therapeutic application in oncology.
|treatment_category=Nutraceuticals
|book_text=Ellagic Acid

This is a family of phenolic compounds present in fruits and nuts, including raspberries,
blueberries, strawberries, pomegranate juice, and walnuts. In laboratory experiments it
has been shown to potently inhibit the growth of various chemical-induced cancers, with
the basis of the effect being an arrest of cell division in the G stage, thus

inducing the programmed cell death known as apoptosis. While there have been no trials
to assess its clinical effects with brain cancer, a recent clinical trial, performed at UCLA
with prostate cancer demonstrate its potential (288). Patients with prostate cancer, whose
PSA levels were rising after initial treatment with either surgery or radiation, drank
pomegranate juice (8 oz/ daily), which contains high levels of eligitannnins (precursors to
ellagic acid). The dependent measure was the rate of increase in the PSA level, which
typically rises at a steady rate for this category of patients. Pomegranate juice produced
�an increase in PSA doubling time, from 15 months at baseline to 54 months after
consuming the juice. Of the 46 patients in the trial, 85% exhibited a notable increase in
the doubling time, and 16% had decreases in their PSA.

Fish oil (source of omega-3 fatty acids)

The major omega-3 fatty acids found in cold-water fish oil, eicosapentaenoic acid (EPA)
and docosahexaenoic acid (DHA), have also been demonstrated to have potent cytotoxic
effects on cancer cells in various laboratory experiments. Part of their mechanism of
action is similar to that of GLA, in that the metabolism of these fatty acids creates high
levels of free radicals. In addition, a recent laboratory study has shown that EPA-treated
tumors showed a significant arrest of cell division due to inhibition of cyclins at the G1
phase of cell division, which resulted in an increased rate of programmed cell death
known as apoptosis (241).

A clinical trial comparing fish-oil supplements versus a placebo has also been reported,
involving patients with several different types of advanced cancer (242). Thirty
malnourished patients suffering from cachexia were randomly assigned to receive 18 g of
fish oil per day or a placebo sugar pill. An additional thirty subjects, adequately
nourished, received a similar random assignment. For both groups the fish oil
significantly increased survival. For the malnourished patients the median survival times,
as estimated from their survivor functions, were 110 days for the patients receiving
placebo and 210 days for patients in the fish oil group. For the adequately nourished
patients, the corresponding numbers were 350 versus 500 days.

In laboratory studies (243) fish oil has also been shown to increase the effectiveness of
chemotherapy and radiation. A phase II trial involving 25 heavily pretreated metastatic
breast cancer patients, used 1.8 g/day of DHA, one of the two major fatty acids in fish oil,
in combination with standard anthracycline-based chemotherapy (244). Patients
previously had failed both chemotherapy and hormone treatments and many had
multiple metastases, including many liver metastases. Because this was a phase II trial,
there was no control group that received chemotherapy alone, but patients were
subdivided according to their level of plasma DHA. The two groups were approximately
equal with respect to all major prognostic variables. Median survival for the high DHA
patients was 34 months, vs. 18 months for the low-DHA patients.

A second clinical trial presented 2200 mg of EPA plus 240 mg of DHA to patients with
advanced non small cell lung cancer (245). Patients either received only the standard of
care of chemotherapy, or the same treatment in combination with daily fish oil. Response
rate (tumor regressions) was 60% in the fish oil group and 26% in those receiving only
the standard of care. One-year survival was 60% in the fish oil group versus 39% in those
receiving only chemotherapy. Chemotherapy toxicity was also decreased in those using
fish oil.

|toxicity_level=1
|links=
|toxicity_explanation=Ellagic Acid, derived from fruits and nuts, is generally considered safe due to its natural origins. It has not been documented to cause specific side effects. However, it's important to note it's still in preclinical and early trial phases, with a focus on cancer prevention rather than treatment. A toxicity level of 1 signifies that it has not been associated with severe harm or side effects, though more extensive clinical research is needed.
}}

Curcumin

2024-11-12T18:29:44Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{TreatmentInfo
|drug_name=Curcumin
|FDA_approval=No (Used as a dietary supplement; not FDA-approved for cancer treatment)
|used_for=Investigational use in cancer treatment and prevention; also used for symptom management like dermatitis from radiotherapy
|clinical_trial_phase=Preclinical studies and early clinical trials
|clinical_trial_explanation=Curcumin is being studied in preclinical and early clinical trials to assess its potential as an anti-cancer agent. While not directly focusing on survival metrics like OS or PFS, these studies explore its biochemical mechanisms that could influence cancer cell behavior and patient symptoms.
|common_side_effects=Generally well-tolerated; bioavailability issues are noted, but can be improved with piperine
|OS_with=Not applicable; studies focus on cellular and symptom management 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=Curcumin has demonstrated potential in laboratory studies for its anti-cancer properties including inhibition of key signaling pathways, promotion of cancer cell apoptosis, and reduction of inflammation and angiogenesis. Its clinical utility in cancer care, particularly in glioblastoma, remains under investigation with early evidence suggesting benefits in symptom management and possibly enhancing the effects of conventional treatments.
|toxicity_level=1
|notes=Curcumin, derived from turmeric, exhibits multiple anti-cancer properties in laboratory studies, including inhibition of tyrosine kinase signaling, angiogenesis, and promotion of apoptosis via NF-kB inhibition. Its bioavailability is limited but can be enhanced with piperine. Clinical evidence of its effectiveness includes reducing dermatitis in breast cancer radiotherapy and decreasing polyp size and number in colon conditions. While promising in laboratory settings for its anti-cancer potential, further research is required to fully understand its clinical efficacy and optimal use in cancer treatment.
|treatment_category=Nutraceuticals
|book_text=Curcumin

This is an ingredient in the Indian cooking spice, turmeric. It has been shown to inhibit
the growth of cancer cells of various types in laboratory studies via numerous different
mechanisms (272). Like genistein, it inhibits the tyrosine kinase signaling and also
inhibits angiogenesis. Perhaps most importantly, it inhibits proteins that prevent
damaged cells from undergoing apoptosis, a family of genes known as nuclear factor
kappa B. Of all of the supplements on this list it is the most potent anti-cancer agent in
laboratory studies. However, it also should be noted that its bioavailability from oral
intake is limited, although bioavailability supposedly is increased when curcumin is
combined with piperine (the main ingredient in black pepper). The Life Extension
Foundation sells a version of curcumin that they claim has much greater bioavailability
than anything else on the market. Despite the limited bioavailability, there is some
evidence of clinical effectiveness. In a study of dermatitis induced by radiotherapy for
breast cancer, a double-blind placebo controlled trial compared a placebo with curcumin
(2 grams three times/day), both of which were taken throughout radiation treatment.
Significantly less dermatitis occurred in patients receiving curcumin (273).

Curcumin has also been used in combination with a second supplement, quercetin, (see
below) for the treatment of an inherited disorder of the colon in which hundreds of
adenomas develop and eventually colon cancer (274). Five patients with the disorder
received 480 mg of curcumin and 20 mg of Quercetin three times daily. Polyp number
and size were assessed at baseline and then six months after starting the supplements.
For all patients there was a decrease in polyp size and number, which was statistically
significant.
|links=* [ClinicalTrials.gov study of Liposomal Curcumin in combination with RT and TMZ](https://clinicaltrials.gov/ct2/show/NCT03552471)
* [Systematic review of clinical effects of curcumin in cancer therapy](https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-5760-2)
* [Antitumor Activity of Curcumin in Glioblastoma](https://www.mdpi.com/1422-0067/21/24/9435)
* [Curcumin and Cancer (PDQ®) - NCI](https://www.cancer.gov/about-cancer/treatment/cam/patient/curcumin-pdq)
|toxicity_explanation=Curcumin, the active ingredient in turmeric, is generally well-tolerated with minimal side effects. As a dietary supplement, it has the lowest toxicity rating. This number (1) represents minimal toxicity. Remember, however, that while curcumin is showing some promising results in laboratory studies, it is not an FDA-approved cancer treatment and is currently under investigation.
}}

Cannabis

2024-11-12T18:29:17Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{TreatmentInfo
|drug_name=Cannabis and Cannabis-derived Products (e.g., Sativex)
|FDA_approval=Sativex is approved in Canada and some European countries for neuropathic pain; cannabis itself is not FDA-approved for cancer treatment
|used_for=Investigational use in cancer treatment, including glioblastoma, for its direct anti-cancer and anti-nausea effects
|clinical_trial_phase=Phase 2 trial for glioblastoma with Sativex combined with temozolomide
|common_side_effects=Varies; cannabis is known for minimal side effects such as dry mouth, red eyes, and increased appetite. Sativex may have additional side effects similar to other cannabis products.
|OS_without=Dose-intense temozolomide alone: Median survival from trial start was 369 days (12.1 months)
|OS_with=Sativex combined with dose-intense temozolomide: Median survival exceeded 550 days (over 18 months)
|PFS_with=Not specifically mentioned; research primarily focused on overall survival and symptomatic relief
|usefulness_rating=4
|notes=In a Phase 2 clinical trial conducted in 2021, Sativex in combination with temozolomide showed promising results for recurrent glioblastoma patients, significantly extending median survival compared to temozolomide alone. This trial underscores the potential of cannabis-based products, like Sativex, as adjunct therapies in cancer treatment, particularly in glioblastoma. These results mark a critical step forward in cannabis research within oncology, warranting further investigation to establish comprehensive benefits and usage protocols.
|treatment_category=Nutraceuticals
|links=
|toxicity_level=1
|toxicity_explanation=The treatment mentioned, Cannabis and Cannabis-derived products like Sativex, generally have minimal side effects. These may include dry mouth, red eyes, and increased appetite, causing mild discomfort rather than serious complications. Therefore, the toxicity is considered low (rated 1 out of 5), meaning it's generally safe with a low risk of harm. However, please note that all individuals may respond differently, and it's important to discuss any new treatments with your healthcare provider.
}}

CBG

2024-11-12T18:28:50Z

69.163.248.232: Updated category= to treatment_category= in TreatmentInfo template

{{TreatmentInfo
|drug_name=Cannabigerol (CBG)
|FDA_approval=No (CBG is a cannabinoid compound under investigation; not FDA-approved for any condition)
|used_for=Investigational use in cancer research for potential anti-tumor effects
|clinical_trial_phase=Preclinical studies and early research
|common_side_effects=Not specifically documented; cannabinoids are generally considered to have a favorable safety profile, but specific studies on CBG's side effects are limited
|OS_with=Not applicable; research is still in preclinical stages, focusing on cellular and animal models
|PFS_with=Not applicable; ongoing studies aim to determine the potential impacts on tumor progression
|usefulness_rating=3
|notes=Cannabigerol (CBG), a non-psychoactive cannabinoid found in the cannabis plant, has garnered attention in preclinical studies for its potential anti-cancer properties. Research has explored CBG's effects on various cancer cell lines, including its ability to induce apoptosis, inhibit cell proliferation, and potentially target cancer stem cells. While findings are promising, indicating CBG could influence pathways involved in cancer progression, conclusive evidence from human clinical trials is awaited to fully establish its efficacy and optimal use in cancer treatment.
|treatment_category=Nutraceuticals
|links=
|toxicity_level=2
|toxicity_explanation=Cannabigerol (CBG) is generally considered safe, as it's a non-psychoactive compound found in the cannabis plant. However, specific studies on CBG’s side effects are limited owing to the fact that it is in the early stages of research. Therefore, a rating of 2 is given, indicating a low level of potential toxicity. However, definitive conclusions about its toxicity can only be made after detailed human clinical trials have been conducted.
}}