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Randomized Phase III Trial Comparing Irinotecan/Cisplatin With Etoposide/Cisplatin in Patients With Previously Untreated Extensive-Stage Disease Small-Cell Lung Cancer

Nasser Hanna, Paul A. Bunn, Jr, Corey Langer, Lawrence Einhorn, Troy Guthrie, Jr, Thaddeus Beck, Rafat Ansari, Peter Ellis, Michael Byrne, Mark Morrison, Subramanian Hariharan, Benjamin Wang, Alan Sandler

From Indiana University; Hoosier Oncology Group, Indianapolis; Michiana Hematology/Oncology, South Bend, IN; University of Colorado Cancer Center, Aurora, CO; Fox Chase Cancer Center, Philadelphia, PA; Baptist Cancer Institute, Jacksonville, FL; Highlands Oncology Group, Springdale, AR; Pfizer Inc, New York, NY; Vanderbilt-Ingram Cancer Center; Vanderbilt-Ingram Community Cancer Center Affiliate Network, Nashville, TN; Juravinski Cancer Centre, Hamilton, Canada; Sir Charles Gairdner Hospital, Nedlands, Australia.

Address reprint requests to Nasser Hanna, MD, Indiana University, 535 Barnhill Dr, RT 473, Indianapolis, IN 46202; e-mail: nhanna{at}iupui.edu

PURPOSE: Etoposide and cisplatin (EP) has been a standard treatment for extensive-disease small-cell lung cancer (SCLC). An earlier phase III trial reported improved survival for patients receiving irinotecan plus cisplatin (IP) versus EP. Our trial was designed to determine if a modified weekly regimen of IP would provide superior survival with less toxicity than EP.

PATIENTS AND METHODS: The primary objective was to compare overall survival in extensive-disease SCLC patients randomly assigned to receive IP (n = 221) or EP (n = 110). Patients were randomly assigned in 2:1 ratio to cisplatin 30 mg/m² intravenously (IV) + irinotecan 65 mg/m² IV on days 1 and 8 every 21 days, or cisplatin 60 mg/m² IV on day 1, and etoposide 120 mg/m² IV on days 1 to 3 every 21 days for at least four cycles, until progressive disease, or until intolerable toxicity resulted.

RESULTS: Selected grade 3/4 toxicities for IP/EP were: neutropenia (36.2% v 86.5%; P < .01), febrile neutropenia (3.7% v 10.4%; P = .06), anemia (4.8% v 11.5%; P = .02), thrombocytopenia (4.3% v 19.2%; P < .01), vomiting (12.5% v 3.8%; P = .04), and diarrhea (21.3% v 0%; P < .01). There was no significant difference in response rates (48% v 43.6%), median time to progression (4.1 v 4.6 months), or overall survival (median survival time, 9.3 months v 10.2 months; P = .74).

CONCLUSION: Treatment with this dose and schedule of IP did not result in improved survival when compared with EP. Fewer patients receiving IP had grade 3/4 anemia, thrombocytopenia, neutropenia, and febrile neutropenia compared with patients receiving EP, but more had grade 3/4 diarrhea and vomiting.

Supported by Pfizer Inc, New York, NY.

Presented in part (abstract and oral presentation) at the 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 13-17, 2005, and at the 11th World Conference on Lung Cancer, Barcelona, Spain, July 3-6, 2005.

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

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Related Editorial

• Reponses to Topoisomerase-I Inhibitors in Extensive Small-Cell Lung Cancer: Chance or Chromosomes?
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• Fractionated Administration of Irinotecan and Cisplatin in Japanese Patients With Extensive-Stage–Disease Small-Cell Lung Cancer
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  JCO 2006 24: 5175 [Full Text]

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