A medical research council randomized trial in patients with primary cerebral non-Hodgkin lymphoma - Cerebral radiotherapy with and without cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy

BACKGROUND. The role of chemotherapy in the treatment of patients with prim ary central nervous system lymphoma (PCL) remains unclear, with no randomiz ed trials available to aid in the interpretation of the current data. The M edical Research Council therefore conducted the current randomized trial to assess the impact on survival of postradiotherapy chemotherapy with cyclop hosphamide, doxorubicin, vincristine, and prednisone (CHOP) in nonimmunocom promised adult patients with pathologically proven PCL. METHODS. After surgery, patients were randomized at a ratio of 1:2 to radio therapy alone (RT: 40 grays [Gy] in 20 fractions to the whole brain followe d by a 14-Gy boost to the tumor plus a 2-cm tumor margin) or to the same ra diotherapy fallowed by six cycles of CHOP chemotherapy given at 3-week inte rvals (RT-CHOP). The target sample size was 90 patients, which allowed 90% power to detect a doubling of the median survival time. RESULTS. Between 1988 and 1995, 53 patients were randomized: Fifteen patien ts were randomized to RT, and 38 patients were randomized to RT-CHOP. The t rial closed earlier than planned through poor accrual. The median patient a ge was 57 years, 57% of the patients were male, and 75% of the patients had unifocal disease. The median number of chemotherapy cycles received was 6 (mean, 4 cycles). Forty-three patients have died, and the median follow-up of survivors is 5 years (range, 1-9 years). There was no evidence of a bene fit from RT-CHOP with respect to overall survival (hazard ratio [HR], 1.19; 95% confidence interval, 0.51-2.76) after adjustment for prognostic factor s (patient age and neurologic performance status) in an analysis in which H R > 1 favored the control (RT) group. CONCLUSIONS. CHOP has no clear role in the postradiotherapy treatment of pa tients with PCL. Chemotherapy is poorly tolerated and largely palliative in older, less fit patients. In younger patients, initial chemotherapy design ed to penetrate the blood-brain barrier warrants further investigation. (C) 2000 American Cancer Society.