A Phase III Trial Evaluating the Combination of Cisplatin, Etoposide, and Radiation Therapy with or Without Tamoxifen in Patients with Limited-stage Small Cell Lung Cancer: Cancer and Leukemia Group B Study (9235)

Based on both clinical and laboratory data that suggested that tamoxifen (TAM) enhanced the effectiveness of cisplatin (DDP)-based chemotherapy regimens, the Cancer and Leukemia Group B (CALGB) designed and initiated a prospective, randomized phase III trial to test the efficacy of the addition of high-dose TAM to a standard chemoradiation regimen of DDP and etoposide (VP-16) in patients with limited-stage small cell lung cancer (LS-SCLC). Between August 6, 1993, and January 15, 1999, 319 patients with LSSCLC were accrued to CALGB 9235. Patients were randomized to receive chemotherapy with or without high-dose TAM. Treatment on the non-TAM containing arm (arm 1) included DDP (80 mg/m2 intravenously day 1 only) and VP-16 (80 mg/m2 intravenously days 1-3) given every 3 weeks for a total of 5 cycles. Patients treated on arm 2 received the identical chemotherapy regimen as described here with the addition of high-dose TAM (80 mg orally twice per day), which was given for 5 days each cycle starting 1 day before the DDP. Thoracic radiation (XRT) given at 200 cGy 5 days per week to a total dose of 50 Gy began on day 1 of cycle 4 of chemotherapy and overlapped with cycle 5. Prophylactic cranial irradiation was offered to all patients who achieved a complete response or near-complete response. A total of 307 patients are evaluable for response. After the completion of the chemoradiation portion of the treatment, the overall response rate (ORR) was 88% for 154 patients treated without tamoxifen and 84% for 153 patients treated with tamoxifen with complete response (CR) rates of 49% and 50%, respectively. The median failure-free survivals of 12.3 months and 10.5 months and the overall survivals of 20.6 months and 18.4 months, respectively, were not statistically significant between the 2 arms. Toxicity was similar with and without tamoxifen. This phase III trial failed to demonstrate a positive effect on either the response or survival for the addition of TAM to standard etoposide-cisplatin-radiation management for patients with LS-SCLC. However, these data continue to support a positive effect of chemoradiation in the treatment of patients with LS-SCLC.