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Property "Has original text" (as page type) with input value "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." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.
Property "Has clinical trial explanation" (as page type) with input value "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." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.
Property "Has original text" (as page type) with input value "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%." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.
Property "Has original text" (as page type) with input value "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." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.
Property "Has original text" (as page type) with input value "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)." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.
Property "Has original text" (as page type) with input value "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)." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.
Property "Has original text" (as page type) with input value "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." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.
Property "Has original text" (as page type) with input value "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." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.
Property "Has original text" (as page type) with input value "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)." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.
Property "Has original text" (as page type) with input value "A variation in the use of dendritic cells first subjected tumor tissue to a heat-shock treatment to elevate the expression of heat-shock proteins, which were extracted from the blood and incubated with dendritic cells from individual patients. In a clinical trial (163) conducted at UCSF and Columbia for patients with recurrent heavily pretreated tumors, the vaccine produced a median survival of 42.6 weeks (about 9.8 months), which compares favorably to the 6-month survival time for historical controls, and is comparable to the 9-11 months when Avastin is used with patients with recurrent tumors.
A subsequent news release from Agenus, Inc, a biotech company sponsoring the research, reported the results of phase II clinical trial in which the heat-shock dendritic vaccine was combined with the standard Stupp protocol (164). Median progression-free survival was 17.8 months and median survival was 23.8 months. This median progression-free survival of 17.8 months is perhaps the longest PFS yet seen in any substantially sized phase 2 trial for newly diagnosed glioblastoma.
Follow-up data (reference 339, abstract 2011) presented at the ASCO 2015 conference revealed that patients with high PD-L1 expression (the ligand for the PD-1 immune checkpoint on the surface of immune cells which is the target for the therapeutic antibodies nivolumab and pembrolizumab) had a median survival of 18 months, while those with low expression of PD-L1 had a median survival of 44.7 months. This finding suggests that efficacy of the heat shock protein peptide vaccine could be greatly improved by co-administration of PD-1 antibodies such as nivolumab or pembrolizumab." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.
