Current Treatment Options for Adults with Glioblastoma

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Inro/General Info 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. Bevacizumab 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 , ... ... middle of paper ... chemoradiotherapy (using TMZ) to radiotherapy alone. DNA isolated and MGMT status established for 206 (36%) of total participant tumors. Methylation of the MGMT promoter was detected in nearly half of those 206 tumors. Patients with MGMT promoter methylation have a longer median survival that those without (18.2 months vs. 12.2 months, P<0.001), regardless of treatment. TMZ has a more pronounced effect in improving survival in patients whose tumors have MGMT promoter methylation than those who do not, but treatment with TMZ leads to prolonged PFS irrespective of methylation status. G7: This study recommends using cryopreserved tumor specimens to determine methylation status and then to treat with TMZ first-line if methylated, noting that methylation of the MGMT promoter gene is a positive prognostic factor for overall survival and progression free survival.

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