C3: median survival of 14.6 months from dx with standard tx of surgery, RT and TMZ. TMZ current first-line chemo agent.
E5: Gliomas are the most common form of primary brain tumors. Grade IV GBM has an overall survival of 12-15 months. Most tumors are past the point of resection when they are discovered. Therefore, healthcare providers must use “salvage therapy” which typically leads to only a 15-16% 6 month PFS.
J10: From the time of recurrence, median survival is 6-8 months.
Current Standard of Treatment
C3: MGMT expression is correlated with resistance to TMZ, but TMZ will eventually overcome this. When comparing standard adjuvant TMZ vs. a dose-dense schedule, there is no difference in overall survival or progression-free survival. However, there is an increased toxicity with dose-dense, with the most commonly experienced toxic side effects including lymphoma and fatigue. Currently no good data, but suggests that patients who progress early may respond differently to continuous dose-dense TMZ.
E5: Current standard therapy is resection of the tumor plus radiotherapy and TMZ.
G7: TMZ dose of 75 mg per square meter of body surface area daily during standard fractionation therapy at 60 Gy for 6-7 weeks and then a dose of 150-200 mg per square meter per day for 5 days each 28 day cycle after radiotherapy.
C3: BRAIN study showed that BEV + standard RT and TMZ vs. RT and TMZ alone increased PFS (87% to 52%, P=0.0001). Some evidence (don’t know where from) that anti-VEGF therapy increases tumor invasion.
E5: Bevacizumab (BEV) is a monoclonal antibody that inhibits VEGF. It had previously been approved for treatment of metastatic colorectal cancer, non-small cell lung cancer, breast, ovarian , and renal cancer. The E5 retrospective study evaluated the success of treatment with MRIs and neurological function with the Response Assessment in Neuro-Oncology. When comparing patients with grade IV GBM treated with the standard radiotherapy and concomitant chemotherapy with TMZ either with or without salvage BEV, the median survival was 8.9 months for those treated with BEV and 5.6 months for patients who did not receive BEV. BEV was first used to treat recurrent malignant glioma in 2005. BEV has a significant survival benefit for patients with grade IV glioma. It may also lead to a decreased required dose of corticosteroids. Side effects of BEV include hypertension and proteinuria.
Breaking the Blood-Brain Barrier (Convection Enhanced Delivery and Gliadel Wafers)
C3: The blood-brain barrier blocks most molecules that are larger than 500 Daltons. BCNU wafers increase mean survival to 13.1 months compared to 10.9 months placebo. FDA approved Gliadel for treatment of newly diagnosed GBM in 2003. Combo of wafers and concomitant radiochemotherapy with TMZ may reduce systemic toxicity because it takes advantage of the sensitizing effects of TMZ and BCNU. Complications of implantation include cerebral edema,...