IS7-7 - Randomized Phase III Study Comparing Etoposide and Cisplatin (EP) with Irinotecan and Cisplatin (IP) Following EP Plus Concurrent Accelerated Hyperfractionated Thoracic Radiotherapy (EP/AHTRT) for the Treatment of Limited-Stage Small-Cell Lung Cancer (LD-SCLC): JCOG0202

Abstract

ABSTRACT Background Four cycles of EP plus AHTRT is the standard treatment for LD-SCLC. IP demonstrated statistically significant overall survival (OS) improvement compared with EP for extensive-stage SCLC (JCOG9511; Noda et al., N Eng J Med, 2002). EP plus AHTRT followed by three cycles of IP is feasible with acceptable toxic effects for LD-SCLC (Kubota et al., CCR, 2005). Method Eligibility criteria included patients with previously untreated LD-SCLC with measurable lesion, ECOG PS of 0-1, age: ≤20, ≤70 years old. Eligible patients received one cycle of EP (etoposide 100 mg/m2 on days 1–3 and cisplatin 80 mg/m2 on day 1) plus AHTRT (1.5 Gy b.i.d. total 45 Gy/3 weeks). Patients who achieved CR, good PR, PR or SD with induction EP/AHTRT were randomized to receive either three cycles of consolidation EP or IP (irinotecan 60 mg/m2 and cisplatin 60 mg/m2 on days 1, 8, 15). Patients with CR or good PR after consolidation chemotherapy received prophylactic cranial irradiation. The primary end point is OS after the randomization. The planned sample size for randomization is 250 with a one-sided alpha of 2.5% and at least 70% power to detect a difference between groups, 30% in EP versus 42.5% in IP group in 3-year survival. Results From September 2002 to September 2006, 281 patients from 36 institutions were registered. After the induction EP/AHTRT, 258 patients were randomized to consolidation EP (n = 129) or IP (n = 129). Patient demographics were well balanced between the two groups. At the final analysis, the superiority of IP in OS was not demonstrated (hazard ratio of IP to EP, 1.085 [95% CI 0.80–1.46]; one-sided P = 0.70, stratified log-rank test). Median OS, 3-year survival and 5-year survival on EP were 3.2 years, 53% and 36%, versus 2.8 years, 47% and 34%, respectively (one-sided P = 0.7030). Median PFS on EP was 1.14 years and 1.03 years on IP (P = 0.7259). Grade 3/4 neutropenia (95%/78%), anemia (35%/39%), thrombocytopenia (21%/5%), neutropenic fever (17%/14%), diarrhea (2%/10%) were observed in EP and IP groups, respectively. Conclusion EP plus AHTRT followed by three cycles of IP failed to demonstrate survival advantage over four cycles of EP plus AHTRT which still is the standard treatment of LD-SCLC.