Randomized trial of radiation therapy (RT) plus dibromodulcitol (DBD) versus RT plus BCNU in high grade astrocytoma

Purpose: We performed a randomized trial to compare survival distributions and toxicity of radiation therapy (RT) and DBD with RT and BCNU in patients with high-grade astrocytoma. Methods: A total of 238 patients with supratentorial grade 3 and grade 4 astrocytoma were studied. Patients were stratified by age, extent of surgery, tumor grade, and performance score and randomly assigned to receive RT 55-60 Gy and either DBD, 200 mg/m(2) orally on Days 1-10 every five weeks or BCNU, 200 mg/m(2) intravenously every seven weeks. Median age was 60 years; 62% were 55 years or older. Eighty-three percent had subtotal resection, 58% had grade 4 tumors, and 83% had performance scores of 0-2. Results: Survival distributions for all patients in the two arms were similar, with median survival of 41 weeks in each arm. Time to progression distributions were virtually identical, with medians of 22 weeks. BCNU produced significantly greater hematologic toxicity; median leukocyte and platelet nadirs on the first cycle were 3.6 vs. 4.7 (P = 0.0001) and 117 vs. 162 (P < 0.0001), and overall platelet nadirs were 80.5 vs. 114 (P = 0.0019). Non-hematologic toxicities were also significantly greater with BCNU, including nausea (57% vs. 31%; P < 0.0001) and vomiting (45% vs. 17%; P < 0.0001). Conclusion: This trial found no evidence of differences in treatment efficacy when either DBD or BCNU is combined with radiation therapy for patients with high-grade astrocytoma.