A179
A randomised trial of procarbazine, CCNU and vincristine (PCV) vs temozolomide (5-day or 21-day schedule) for recurrent high grade glioma (MRC BR12, ISRCTN83176944)
Michael Brada, BR12 Collaborators
Institute of Cancer Research, Sutton, UK
Background
Nitrosourea-based chemotherapy (NBC) is widely used for patients with recurrent high grade glioma (HGG) not receiving prior chemotherapy. Although Temozolomide (TMZ) is increasingly used, this is the first randomised trial to report a direct comparison with NBC. We also investigate two different TMZ dosing schedules.
Method
Chemo-naïve patients with radiologically confirmed, recurrent HGG were randomised 2:1:1 to PCV, TMZ-5, and TMZ-21. TMZ schedules: 200mg/m2 for 5 days (TMZ-5) or 100mg/m2 for 21 days (TMZ-21), both repeated every 28 days for 9 cycles or until progression. PCV: procarbazine 100mg/m2 p.o. days 1-10, CCNU 100mg/m2 p.o. day 1 and vincristine 1.5mg/m2 (max 2mg) i.v. day 1; cycles repeated 6 weekly for 6 cycles or until progression.
The primary comparison is PCV vs. TMZ (either schedule); the primary outcome is
survival. The trial is powered to detect a 2-3 month increase in median
survival with TMZ. 500 patients randomised over 4 years were anticipated, with
a planned subgroup analysis in 300 glioblastoma multiforme (GBM) patients.
Progression-free survival (PFS) at 3 months is the primary outcome for the
comparison of the two TMZ schedules.
Results
The trial closed 31/01/08 with 447 patients randomised (317 GBM). We will conduct the primary analysis after 380 deaths (anticipated 06/08). Kaplan-Meier curves will be presented with hazard ratios and 95% confidence intervals and compared by the logrank test. Overall survival: TMZ vs. PCV (all patients and GBM subgroup). PFS: PCV vs. TMZ and TMZ-5 vs. TMZ-21. Compliance and toxicity data will be presented by trial arm.
