Phase III Trial of Irinotecan/Cisplatin Compared With Etoposide/Cisplatin in Extensive-Stage Small-Cell Lung Cancer: Clinical and Pharmacogenomic Results From SWOG S0124

作者：Primo N. Lara, Ronald B. Natale, John Crowley, Heinz Josef Lenz, Mary Weber Redman, Jane E. Carleton, James R. Jett, Corey Jay Langer, J. Philip Kuebler, Shaker R. Dakhil, Kari Chansky, David R. Gandara · 发表于：Journal of Clinical Oncology · 年份：2009 · DOI：10.1200/jco.2008.20.1061 · 被引用次数：525 · 研究领域：Lung Cancer Research Studies、Cancer therapeutics and mechanisms、Lung Cancer Treatments and Mutations

PURPOSE: Irinotecan plus cisplatin (IP) improved survival over etoposide plus cisplatin (EP) in Japanese patients with extensive-stage small-cell lung cancer (E-SCLC). To confirm those results and discern the potential role of population-related pharmacogenomics (PG) in outcomes, we conducted a large randomized trial of identical design to the Japanese trial in North American patients with E-SCLC. PATIENTS AND METHODS: Patients were randomly assigned to IP (irinotecan 60 mg/m(2) on days 1, 8, and 15; cisplatin 60 mg/m(2) day 1, every 4 weeks) or EP (etoposide 100 mg/m(2) on days 1 through 3; cisplatin 80 mg/m(2) day 1, every 3 weeks). Blood specimens for genomic DNA analysis were collected before random assignment in 169 patients. RESULTS: Of 671 patients, 651 were eligible (324 and 327 patients in the IP and EP arms, respectively). Response rates with IP and EP were 60% and 57%, respectively (P = .56). Median progression-free survival for IP and EP was 5.8 and 5.2 months, respectively (P = .07). Median overall survival for IP and EP was 9.9 and 9.1 months, respectively (P = .71). Severe diarrhea was more common with IP (19% v 3%); severe neutropenia and thrombocytopenia were higher with EP versus IP (68% v 33% and 15% v 4%, respectively). PG analysis showed that ABCB1 (C3435T)T/T (membrane transport) was associated with IP-related diarrhea; UGT1A1 (G-3156A)A/A (drug metabolism) was associated with IP-related neutropenia. CONCLUSION: This large North American trial failed to ...