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Originally published as JCO Early Release 10.1200/JCO.2007.14.4824 on March 31 2008 © 2008 American Society of Clinical Oncology. Phase III Trial of Maintenance Gefitinib or Placebo After Concurrent Chemoradiotherapy and Docetaxel Consolidation in Inoperable Stage III Non–Small-Cell Lung Cancer: SWOG S0023
From the University of Kansas Medical Center, Kansas City, MO; Southwest Oncology Group Statistical Center, Seattle, WA; University of Colorado Health Sciences Center, Denver, CO; Loyola University School of Medicine, Maywood, IL; Mayo Clinic Rochester, Rochester, MN; University of California at Davis, Sacramento, CA; and Toronto-Sunnybrook Regional Cancer Center, Toronto, Ontario, Canada Corresponding author: Karen Kelly, MD, University of Kansas Medical Center, 4030 Robinson Hall, Mail Stop 1027, 3901 Rainbow Blvd, Kansas City, KS 66160; e-mail: kkelly{at}kumc.edu Purpose: Early clinical studies with gefitinib showed promising efficacy and mild toxicity in patients with advanced non–small-cell lung cancer (NSCLC). Thus, gefitinib was an ideal agent to evaluate in a maintenance setting in stage III disease. Patients and Methods: Untreated patients with stage III NSCLC, a performance score of 0 to 1, and adequate organ function were eligible. All patients received cisplatin 50 mg/m2 on days 1 and 8 plus etoposide 50 mg/m2 on days 1 to 5, every 28 days for two cycles with concurrent thoracic radiation (1.8- to 2-Gy fractions per day; total dose, 61 Gy) followed by three cycles of docetaxel 75 mg/m2. Patients whose disease did not progress were randomly assigned to gefitinib 250 mg/d or placebo until disease progression, intolerable toxicity, or the end of 5 years. The planned sample size was 672 patients to confer power of 0.89 to detect a 33% increase over the expected median survival time of 21 months (one-sided P = .025, log-rank test). Random assignment was stratified by stage, histology, and measurable versus nonmeasurable disease. Results: Enrollment began in July 2001. An unplanned interim analysis conducted in April 2005 rejected the alternative hypothesis of improved survival at the P = .0015 level for 243 randomly assigned patients. The study closed, and preliminary results were reported. Now, with a median follow-up time of 27 months, median survival time was 23 months for gefitinib (n = 118) and 35 months for placebo (n = 125; two-sided P = .013). The toxic death rate was 2% with gefitinib compared with 0% for placebo. Conclusion: In this unselected population, gefitinib did not improve survival. Decreased survival was a result of tumor progression and not gefitinib toxicity. published online ahead of print at www.jco.org on March 31, 2008. Supported in part by AstraZeneca and Sanofi-aventis and the following National Cancer Institute, Department of Health and Human Services, Public Health Service Cooperative Agreement Grants No.: CA38926, CA32102, CA46441, CA35431, CA37663, CA46282, CA35261, CA14028, CA35119, CA45377, CA35178, CA45450, CA42777, CA67575, CA20319, CA04919, CA35090, CA46368, CA35176, CA45808, CA45560, CA35192, CA52654, CA63844, CA35281, CA45807, CA35128, CA35262, CA63845, CA74647, CA86780, CA63850, CA13612, CA45461, CA63848, CA11083, CA58882, and CA74811. Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL. Authors disclosures of potential conflicts of interest and author contributions are found at the end of this article. Related Editorial
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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