An exploratory survival analysis of anti-angiogenic therapy for recurrent malignant glioma.

Recent clinical trial results suggest that anti-angiogenic therapy may be effective against recurrent malignant glioma. Though these treatments prolong progression-free survival, the extent to which they prolong overall survival is unknown. We pooled data from 34 patients treated at a single institution on phase II clinical trials of bevacizumab and cediranib, and we compared these data to 18 patients treated on clinical trials of cytotoxic chemotherapies. In univariate and multivariate analyses, treatment group was a significant predictor of progression-free but not overall survival. Median progression-free survival was 8 vs. 22 weeks in patients treated with cytotoxic as compared to anti-angiogenic therapy (P = 0.01). Median overall survival was nearly identical in the two groups (39 vs. 37 weeks). The results of this exploratory analysis suggest that anti-angiogenic therapy may fail to prolong overall survival in patients with recurrent malignant glioma. If this conclusion proves correct, progression-free survival may be an inappropriate endpoint for phase II trials of anti-angiogenic therapies.

A pilot safety study of lenalidomide and radiotherapy for patients with newly diagnosed glioblastoma multiforme.

PURPOSE: To define the maximum tolerated dose (MTD) of lenalidomide, an analogue of thalidomide with enhanced immunomodulatory and antiangiogenic properties and a more favorable toxicity profile, in patients with newly diagnosed glioblastoma multiforme (GBM) when given concurrently with radiotherapy. PATIENTS AND METHODS: Patients with newly diagnosed GBM received radiotherapy concurrently with lenalidomide given for 3 weeks followed by a 1-week rest period and continued lenalidomide until tumor progression or unacceptable toxicity. Dose escalation occurred in groups of 6. Determination of the MTD was based on toxicities during the first 12 weeks of therapy. The primary endpoint was toxicity. RESULTS: Twenty-three patients were enrolled, of whom 20 were treated and evaluable for both toxicity and tumor response and 2 were evaluable for toxicity only. Common toxicities included venous thromboembolic disease, fatigue, and nausea. Dose-limiting toxicities were eosinophilic pneumonitis and transaminase elevations. The MTD for lenalidomide was determined to be 15 mg/m(2)/d. CONCLUSION: The recommended dose for lenalidomide with radiotherapy is 15 mg/m(2)/d for 3 weeks followed by a 1-week rest period. Venous thromboembolic complications occurred in 4 patients, and prophylactic anticoagulation should be considered.