Originally published as JCO Early Release 10.1200/JCO.2008.20.1061 on April 6 2009

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lara, P. N. Articles by Gandara, D. R. Search for Related Content PubMed PubMed Citation Articles by Lara, P. N., Jr Articles by Gandara, D. R. Social Bookmarking                            What's this?

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

From the University of California Davis Cancer Center, Sacramento; Cedars Sinai Cancer Center; University of Southern California Norris Cancer Center, Los Angeles, CA; Southwest Oncology Group Statistical Center, Seattle, WA; North Shore–Long Island Jewish Health System, Manhasset, NY (Cancer and Leukemia Group B); Mayo Clinic, Rochester, MN (North Central Cancer Treatment Group); University of Pennsylvania Abramson Cancer Center, Philadelphia, PA (Eastern Cooperative Oncology Group); Columbus Community Clinical Oncology Program, Columbus, OH; and Wichita Community Clinical Oncology Program, Wichita, KS.

Corresponding author: Primo N. Lara Jr, MD, University of California Davis Cancer Center, 4501 X St, Sacramento, CA 95817; e-mail: primo.lara{at}ucdmc.ucdavis.edu.

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/m² on days 1, 8, and 15; cisplatin 60 mg/m² day 1, every 4 weeks) or EP (etoposide 100 mg/m² on days 1 through 3; cisplatin 80 mg/m² 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 confirm the previously reported survival benefit observed with IP in Japanese patients. Both regimens produced comparable efficacy, with less hematologic and greater gastrointestinal toxicity with IP. These results emphasize the potential importance of PG in interpreting trials of cancer therapy.

Supported in part by the following Public Health Service Cooperative Agreement grants awarded by the National Cancer Institute, United States Department of Health and Human Services: Grants No. CA32102, CA38926, CA46441, CA58882, CA35261, CA35431, CA35119, CA22433, CA58658, CA11083, CA46441, CA37981, CA45560, CA58861, CA04919, CA67663, CA12644, CA45807, CA67575, CA35281, CA20319, CA45808, CA35178, CA58416, CA14028, CA76448, CA35090, CA52654, CA58882, CA76447, CA76429, CA35128, CA46282, CA63848, CA46113, CA58723, CA63844, CA46368, CA35192, CA68183, CA45450, CA35176, CA76132, CA13612, CA16385, CA45377, CA63850, CA74647, CA58348, CA42777, CA35279 (CALGB), CA27525, and CA21115 from the Eastern Cooperative Oncology Group; Pfizer Inc; and Grant No. CA114771 from the National Institutes of Health Strategic Partnering to Evaluate Cancer Signatures in Lung Cancer.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical trial information can be found for the following: NCT00045162.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?