Temozolomide (TMZ) and bevacizumab (BV) as initial treatment for unresectable or multifocal glioblastoma multiforme (GBM).

e13025 Background: GBMs are vascular tumors and inherently resistant to therapy. The prognosis for patients is poor with a median survival of 9-15 months. Patients with unresectable or multifocal GBMs have an even poorer prognosis, with a median survival of 6-8 months. Given the angiogenic phenotype of GBM, we conducted a phase II trial of upfront BV and 5-day TMZ in newly diagnosed unresectable or multifocal GBMs. METHODS: Patients had histologically documented newly diagnosed GBMs that were unresectable or multifocal. Patients received up to 4 cycles of temozolomide at 200 mg/m(2)/d days 1-5 and BV at 10 mg/kg on days 1 and 14 in a 28 day cycle. An MRI was performed after every cycle and patients continued on therapy as long as there was no tumor progression, grade 4 non-hematologic toxicity or recurrent grade 4 hematologic toxicity after a dose reduction to 150 mg/m(2)/d. The primary endpoint was tumor response using the modified MacDonald criteria plus FLAIR and T2 sequences to evaluate non-enhancing tumor. Results were evaluated by two independent reviewers. RESULTS: 41 patients were enrolled between October 2007 and September 2008 and 31 patients were analyzed after completion of cycle 2. As the best response, there were 8 (25.8%) partial responses, 19 (61.3 %) patients with stable disease, and 4(12.9 %) had disease progression. 19 of the 41 patients enrolled completed four cycles without tumor progression. The regimen was tolerable, with 3 grade 4 hematologic toxicities including neutropenia and thrombocytopenia. There were 2 grade 4 non-hematologic toxicities, including pulmonary embolism. There were two CNS hemorrhages. The median PFS was 3.6 months (2.9 months, 4.4 months) and the median OS was 4.5 months (3.7 months, 5.3 months). CONCLUSIONS: Upfront temozolomide and bevacizumab was well tolerated, but synergistic chemotherapy or growth factor inhibitors need to be added to produce meaningful clinical benefit, particularly for unresectable or multifocal GBM. No significant financial relationships to disclose.

Duke Scholars

Author James Emmett Herndon II Biostatistics & Bioinformatics, Division of Biostatistics

Author Henry Seth Friedman Neurosurgery, Neuro-Oncology

Author Darell Doty Bigner Neurosurgery