Adult Brain Tumors Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Recurrent Adult Brain Tumors
Re-resection of recurrent brain tumors is used in some patients. However, the majority of patients do not qualify because of a deteriorating condition or technically inoperable tumors. The evidence is limited to noncontrolled studies and case series on patients who are healthy enough and have small enough tumors to technically debulk. The impact of reoperation versus patient selection on survival is not known.
Carmustine wafers have been investigated in the setting of recurrent malignant gliomas, but the impact on survival is less clear than at the time of initial diagnosis and resection. In a multicenter randomized, placebo-controlled trial, 222 patients with recurrent malignant primary brain tumors requiring reoperation were randomly assigned to receive implanted carmustine wafers or placebo biodegradable wafers. Approximately half of the patients had received prior systemic chemotherapy. The two treatment groups were well balanced at baseline. Median survival was 31 versus 23 weeks in the two groups. The statistical significance between the two overall survival (OS) curves depended upon the method of analysis. The hazard ratio (HR) for risk of dying in the direct intention-to-treat comparison between the two groups was 0.83 (95% confidence interval [CI], 0.63-1.10; P = .19). The baseline characteristics were similar in the two groups, but the investigators did an additional analysis, adjusting for prognostic factors, because they felt that even small differences in baseline characteristics could have a powerful influence on outcomes. In the adjusted proportional hazards model, the HR for risk of death was 0.67 (95% CI, 0.51-0.90, P = .006). The investigators put their emphasis on this latter analysis and reported this as a positive trial.[Level of evidence: 1iA] However, a Cochrane Collaboration systematic review of chemotherapeutic wafers for high-grade glioma focused on the unadjusted analysis and reported the same trial as negative.
In 2009, the U.S. Food and Drug Administration (FDA) granted accelerated approval of bevacizumab monotherapy for patients with progressive glioblastoma. The indication was granted under the FDA's accelerated approval program that permits the use of certain surrogate endpoints or an effect on a clinical endpoint other than survival or irreversible morbidity as bases for approvals of products intended for serious or life-threatening illnesses or conditions. The approval was based on the demonstration of improved objective response rates observed in two historically controlled, single-arm, or noncomparative phase II trials.[3,4][Level of evidence: 3iiiDiv]