Role of a second chemotherapy in recurrent malignant glioma patients who progress on a bevacizumab-containing regimen

Abstract

2008 Background: Bevacizumab is a humanized VEGF monoclonal antibody with promising activity in recurrent glioblastomas, alone and in combination with irinotecan. Patients who progress on this regimen are frequently maintained on bevacizumab and the concurrent chemotherapeutic agent is changed. The benefit of this therapeutic strategy is unknown. Methods: We retrospectively reviewed the clinical features and radiologic studies of 44 patients with recurrent malignant glioma who progressed on a bevacizumab-containing regimen and were then treated with an alternate bevacizumab-containing regimen. All patients received bevacizumab 10 mg/kg IV every 2 weeks. As the initial bevacizumab-containing regimen, 37 patients received irinotecan, 4 bevacizumab alone, 1 temozolomide and 2 carboplatin. As a second bevacizumab-containing regimen, 32 patients received carboplatin, 6 irinotecan, 2 BCNU, 1 CCNU, 1 etoposide, 1 erlotinib/rapamycin and 1 erlotinib. There was no limit on the number of prior therapies. Clinical characteristics and outcomes were reviewed. Tumor progression was determined by a combination of clinical status and radiographic changes. Results: Patient characteristics were 28 male, 16 female; median age 49 years (range 22–72); median KPS prior to receiving both regimens 70 (range 60–100 with first regimen and 40–100 with second regimen); median prior chemotherapy regimens including the first bevacizumab-containing regimen was 3 (range 2–5). Median PFS on first bevacizumab-containing regimen was 123.5 days. 6 month PFS was 33%. Median PFS on the second bevacizumab-containing regimen was 40 days (range 14 to 359 days). 6 month PFS was 2%. The number of grade 3/4 adverse events was similar between the two groups (7 with the first regimen and 8 with the second regimen). Conclusions: Patients with malignant gliomas who progress following treatment with a bevacizumab-containing chemotherapeutic regimen generally respond poorly to a second chemotherapy combined with bevacizumab. Other therapeutic options should be considered for these patients. No significant financial relationships to disclose.