Phase II Study of Induction Cisplatin and Irinotecan Followed by Concurrent Carboplatin, Etoposide, and Thoracic Radiotherapy for Limited-Stage Small-Cell Lung Cancer, CALGB 30206

Introduction: We sought to determine the efficacy of using both irinotecan- and etoposide-containing regimens sequentially for patients with untreated limited-stage small-cell lung cancer. Methods: Patients with untreated, measurable, limited-stage small-cell lung cancer with performance status 0 to 2, and adequate organ function were eligible. Treatment consisted of induction with cisplatin 30 mg/m(2) and irinotecan 65 mg/m(2) intravenously on day 1 and 8, every 21 days for two cycles. Beginning day 43, daily chest irradiation to 70 Gy was administered concurrently with carboplatin area under curve 5 on day 1, and etoposide 100 mg/m2 on days 1 to 3, every 21 days for three cycles. The primary objective was to differentiate between 45% and 60% 2-year survival. Results: Two induction cycles were delivered to 72 of 75 eligible patients (96%) and all planned treatment was delivered to 59 patients (79%). Cisplatin and irinotecan induction chemotherapy resulted in complete responses in 7% and partial responses in 64% (response rate 71%, 95% confidence interval [CI], 59%-81%). The best response to all therapy included 88% complete or partial responses (95% CI, 78%-94%). With median follow-up of 57 months, the median progression-free survival and overall survival are 12.6 (95% CI, 9.4-14.7) and 18.1 months (15.8-22.9), respectively. The 1- and 2-year survival was 69% and 31%, respectively. Frequent (>20%) grade 3 and 4 toxicities were neutropenia in 84%, hemoglobin in 36%, platelets in 51%, esophagitis in 22%, and dehydration in 24%. There were no fatal toxicities. Conclusions: This treatment regimen of irinotecan-cisplatin induction chemotherapy followed by 70 Gy concurrent radiation and etoposide-carboplatin had tolerable toxicity but did not meet the pre-planned 2-year survival target for further development.