Treatment of brain metastases of small-cell lung cancer: Comparing teniposide and teniposide with whole-brain radiotherapy - A phase III study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group

Purpose: Approximately 60% of patients with small-cell lung cancer (SCLC) develop brain metastases, Whole-brain radiotherapy (WBRT) gives symptomatic improvement in more than 50% of these patients. Because brain metastases are a sign of systemic progression, and chemotherapy was found to be effective as well, ir becomes questionable whether WBRT is the only appropriate therapy in this situation. Patients and Methods: In a phase III study, SCLC patients with brain metastases were randomized to receive teniposide with or without WBRT. Teniposide 120 mg/m(2) wets given intravenously three rimes a week, every 3 weeks. WBRT(10 fractions of 3 Gy) had to start within 3 weeks from the start of chemotherapy. Response was measured clinically and by computed tomography of the brain. Results: One hundred twenty eligible patients were randomized. A 57% response race wets seen in the combined-modality arm (95% confidence interval [CI], 43% to 69%), and a 22% response rate was seen in the teniposide-alone arm (95% CI, 12% to 34%) (P <.001). Time to progression in the brain was longer in the combined-modality group (P =.005). Clinical response and response outside the brain were nor different. The median survival time was 3.5 months in the combined-modality arm and 3.2 months in the teniposide-alone arm. Overall survival in both groups was not different (P =.087). Conclusion: Adding WBRT to teniposide results in a much higher response rate of brain metastases and in a longer time to progression of brain metastases than teniposide alone. Survival was poor in both groups and not significantly different. J Clin Oncol 18:3400-3408. (C) 2000 by American Society of Clinical Oncology.