Treatment > PCV

Meeting Abstract

Medical Research Council (MRC) Randomised Trial of Adjuvant Chemotherapy in High Grade Glioma (HGG)

M Brada, DG Thomas, NM Bleehen, JT Roberts, F Senanayake, P Abram, PL Lantos, TH Moss, JW Ironside, JB Whaley, SP Stenning

Background. Meta-analyses of published literature suggest a survival benefit to adjuvant chemotherapy for HGG, which individual small trials have been unable to demonstrate reliably. 
The MRC Brain Tumour Working Party initiated a large randomised trial in an attempt to provide a definitive answer. 

Design. Following surgery, patients aged <=70, with histologically proven HGG (WHO grades 3 or 4), were randomised to radiotherapy (RT) alone (institutional choice, either 45Gy/20 fractions, 60Gy/30 fractions or other radical dose), or RT plus PCV (RTPCV) q 6 weeks: procarbazine 100 mg/m[Superscript 2] d 1--10, CCNU 100 mg/m[Superscript 2] d1, vincristine 1.5 mg/m[Superscript 2] (max 2mg) day 1. 
Target sample size was 600 patients, to reliably detect a 10% increase in 2 year survival. 

Results. Between September 1988 and May 1997, 15 UK centres randomised 674 patients (339 allocated RT, 335 allocated RTPCV). 
All cases were independently reviewed by a neuropathology panel. 
Mean age was 52 years, 42% had partial and 16% macroscopic removal; WHO performance status was <= grade 1 in 75% of patients pre-RT; 76% had WHO grade 4 tumours. 
The planned RT schedule was 60Gy in 74% of patients in each arm. 
The median number of chemotherapy cycles received was 3; no grade 3 or 4 neurotoxicity was seen. 
With median follow-up for survivors of 1 year, 544 patients have died, 272 in each arm. 
Median survival was 9.5 months for RT, 10 months for RTPCV, hazard ratio = 0.95, 95% CI (0.80, 1.12) logrank p = 0.55. Tests for interaction revealed no significant differences in treatment effect according to tumour grade, age, performance status or extent of neurosurgery. 

Conclusions. This trial shows no benefit to PCV chemotherapy, and current data exclude an increase in median survival of >10 weeks, and in 1 or 2 year survival of >7%. 
This suggests that no-chemotherapy control arms remain ethical in randomised trials in HGG.

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