Effects of bevacizumab plus irinotecan on response and survival in patients with recurrent malignant glioma: a systematic review and survival-gain analysis

BACKGROUND: The combination of bevacizumab and irinotecan is a new chemotherapy protocol increasingly used for recurrent malignant glioma. Results from phase II trials suggest this drug combination is beneficial to patients, but no conclusive comparisons between this and other treatment protocols have been published. METHODS: We performed a systematic review and survival gain analysis of phase II studies to evaluate the efficacy and safety of bevacizumab plus irinotecan treatment. To do this, we utilized a preexisting database from which the mean overall survival and response rate of patients could be predicted. Survival gain, which characterized the influence of treatment, was defined as the difference between observed and predicted mean overall survival. Response gain was calculated similarly. RESULTS: 741 cohorts were enrolled in the database. Among them, 282 cohorts were based on recurrent adult HGG, mean reported median overall survival was 10.96 ± 8.4 months, and mean response rate was 18.9% ± 20.5. We found that compared with other treatment protocols, bevacizumab plus irinotecan largely improved response rates (P = 0.00002) and had a possible moderate effect on overall survival time (P = 0.024). Hemorrhage, thromboembolic complications, and gastrointestinal toxicities were the most frequently reported side effects. CONCLUSION: The combination of bevacizumab and irinotecan might improve outcome in patients with recurrent malignant glioma. Randomized controlled trials are recommended to evaluate this treatment protocol and the additional value of irinotecan.