Temozolomide Versus Procarbazine, Lomustine, and Vincristine in Recurrent High-Grade Glioma

Brada, M. et al. (2010) Temozolomide Versus Procarbazine, Lomustine, and Vincristine in Recurrent High-Grade Glioma. Journal of Clinical Oncology, 28(30), pp. 4601-4608. (doi:10.1200/JCO.2009.27.1932)

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Publisher's URL: http://dx.doi.org/10.1200/JCO.2009.27.1932

Abstract

Purpose Temozolomide (TMZ) is an alkylating agent licensed for treatment of high-grade glioma (HGG). No prospective comparison with nitrosourea-based chemotherapy exists. We report, to our knowledge, the first randomized trial of procarbazine, lomustine, and vincristine (PCV) versus TMZ in chemotherapy-naive patients with recurrent HGG. Patients and Methods Four hundred forty-seven patients were randomly assigned to PCV (224 patients) or TMZ (sub-random assignment: TMZ-5 [200 mg/m(2) for 5 days, 112 patients] or TMZ-21 [100 mg/m(2) for 21 days, 111 patients]) for up to 9 months or until progression. The primary outcomes were survival (PCV v TMZ) and 12-week progression-free survival (PFS; TMZ-5 v TMZ-21). This study is registered as ISRCTN83176944. Results Percentages of patients completing 9 months of treatment in the PCV, TMZ-5, and TMZ-21 arms were 17%, 26%, and 13%, respectively. Major toxicity was similar across all three groups. With a median follow-up time of 12 months and 382 deaths, there was no clear survival benefit when comparing PCV with TMZ (hazard ratio [HR], 0.91; 95% CI, 0.74 to 1.11; P = .350). For TMZ-5 versus TMZ-21, 12-week PFS rates were similar (63.6% and 65.7%, respectively; P = .745), but TMZ-5 improved overall PFS (HR, 1.38; 95% CI, 1.05 to 1.82; P = .023), survival (HR, 1.32; 95% CI, 0.99 to 1.75; P = .056), and global quality of life (49% v 19% improved > 10 points at 6 months, respectively; P = .005). Conclusion Although TMZ (both arms combined) did not show a clear benefit compared with PCV, comparison of the TMZ schedules demonstrated that the 21-day schedule was inferior to the 5-day schedule in this setting. This challenges the current understanding of increasing TMZ dose-intensity by prolonged scheduling.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Rampling, Professor Roy
Authors: Brada, M., Stenning, S., Gabe, R., Thompson, L.C., Levy, D., Rampling, R., Erridge, S., Saran, F., Gattamaneni, R., Hopkins, K., Beall, S., Collins, V. P., and Lee, S.-M.
College/School:College of Medical Veterinary and Life Sciences
Journal Name:Journal of Clinical Oncology
ISSN:0732-183X

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