A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse

作者：W.K. Alfred Yung, Robert E. Albright, Jeffrey J. Olson, Ruth K. Fredericks, Karen Fink, Michael D. Prados, M. Brada, A. Spence, Raymond J. Hohl, William Shapiro, Michael Glantz, H. S. Greenberg, Robert G. Selker, Nicholas A. Vick, R. Rampling, Henry S. Friedman, Peter C. Phillips∥, Janet Bruner, N C Yue, David Osoba, Sara Zaknoen, Victor A. Levin · 发表于：British Journal of Cancer · 年份：2000 · DOI：10.1054/bjoc.2000.1316 · 被引用次数：941 · 研究领域：Glioma Diagnosis and Treatment、Brain Metastases and Treatment、Management of metastatic bone disease

A randomized, multicentre, open-label, phase II study compared temozolomide (TMZ), an oral second-generation alkylating agent, and procarbazine (PCB) in 225 patients with glioblastoma multiforme at first relapse. Primary objectives were to determine progression-free survival (PFS) at 6 months and safety for TMZ and PCB in adult patients who failed conventional treatment. Secondary objectives were to assess overall survival and health-related quality of life (HRQL). TMZ was given orally at 200 mg/m(2)/day or 150 mg/m(2)/day (prior chemotherapy) for 5 days, repeated every 28 days. PCB was given orally at 150 mg/m(2)/day or 125 mg/m(2)/day (prior chemotherapy) for 28 days, repeated every 56 days. HRQL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 [+3]) and the Brain Cancer Module 20 (BCM20). The 6-month PFS rate for patients who received TMZ was 21%, which met the protocol objective. The 6-month PFS rate for those who received PCB was 8% (P = 0.008, for the comparison). Overall PFS significantly improved with TMZ, with a median PFS of 12.4 weeks in the TMZ group and 8.32 weeks in the PCB group (P = 0.0063). The 6-month overall survival rate for TMZ patients was 60% vs. 44% for PCB patients (P = 0.019). Freedom from disease progression was associated with maintenance of HRQL, regardless of treatment received. TMZ had an acceptable safety profile; most adverse events were mild or moderate in severity.