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

Purpose: Approximately 60% of patients with small-cell lung cancer (SCLC) d evelop brain metastases, Whole-brain radiotherapy (WBRT) gives symptomatic improvement in more than 50% of these patients. Because brain metastases ar e a sign of systemic progression, and chemotherapy was found to be effectiv e as well, ir becomes questionable whether WBRT is the only appropriate the rapy in this situation. Patients and Methods: In a phase III study, SCLC patients with brain metast ases were randomized to receive teniposide with or without WBRT. Teniposide 120 mg/m(2) wets given intravenously three rimes a week, every 3 weeks. WB RT(10 fractions of 3 Gy) had to start within 3 weeks from the start of chem otherapy. Response was measured clinically and by computed tomography of th e brain. Results: One hundred twenty eligible patients were randomized. A 57% respon se 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 ar m (95% CI, 12% to 34%) (P <.001). Time to progression in the brain was long er in the combined-modality group (P =.005). Clinical response and response outside the brain were nor different. The median survival time was 3.5 mon ths 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 rat e of brain metastases and in a longer time to progression of brain metastas es than teniposide alone. Survival was poor in both groups and not signific antly different. J Clin Oncol 18:3400-3408. (C) 2000 by American Society of Clinical Oncology.