Multi-drug versus single agent chemotherapy for high grade astrocytoma; Results of a meta-analysis

Background: The addition of chemotherapy to postoperative radiation therapy in the treatment of high grade astrocytoma results in a modest increase in 12 and 24 month survival. It is, at present, unclear whether single agent or combination drug therapy constitutes the best drug regimen for these patients. Despite this uncertainty, multi-drug regimens have become standard therapy for some high grade astrocytomas. Methods: One year survival data derived from over 2100 patients enrolled in 9 randomized clinical trials were analyzed using the meta-analytic techniques previously described by Peto et al. This analysis compared the proportion of patients surviving one year treated with multi-drug regimens versus single agent treatment (usually BCNU). All patients included in this analysis also underwent surgery and radiation therapy as part of their clinical management. Results: A summary odds ratio was calculated following a statistical analysis showing a lack of heterogeneity among the included studies in terms of their estimate of effect. The calculated Peto odds ratio was 1.22 with a 95% confidence interval of 0.99-1.36. These data indicate that combination drug treatment is associated with an approximately 22% decreased 1 year survival as compared with single agent therapy. Conclusion: This analysis suggests that the available data do not support the use of combination chemotherapy regimens in this patient population. Additional randomized clinical trials are needed to clearly determine whether any multidrug treatment scheme is superior to currently available single agent therapies.