Superiority of PCNU over AZQ in the treatment of primary brain tumors: results of a prospective randomized trial (81-20) by the brain tumor study group

Purpose: A two-arm randomized clinical trial was performed to determine the efficacy of PCNU and AZQ in the treatment of de novo or recurrent primary brain tumors. An additional objective was to gather information on the administration and toxicity of these compounds, supplementing that obtained previously in phase I/II studies. Methods: During 1982 and 1983 the Brain Tumor Study Group randomized 152 adult patients with primary brain tumors to receive PCNU 75-100 mg/m² intravenously (IV) every 8 weeks or AZQ 15 mg/m² IV once a week for 4 weeks, every 6-8 weeks. All patients who had not received 'full dose' radiotherapy before randomization received it concurrently with the first course of protocol chemotherapy. The data were analyzed for the total randomized population (RP), and for 130 patients in the valid study group (VSG) formed by excluding 22 patients for whom the histologic diagnosis was not documented by central review. Results: Median survival times were 11.0 months for the PCNU group and 8.4 months for the AZQ group. The difference in survival curves was statistically significant for the RP (p=0.01) and the VSG (p=0.02). Lifetable analysis of the VSG showed estimated 2-year survivals of 34% for PCNU and 11% for AZQ. The advantage of PCNU remained significant (p=0.006) after adjustment for histopathologic category, age, initial performance status, and interval from initial reported surgery. Myelosuppression was the principal toxicity in both groups.