Originally published as JCO Early Release 10.1200/JCO.2009.21.8909 on August 31 2009

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Phase III Trial of Four Cisplatin-Containing Doublet Combinations in Stage IVB, Recurrent, or Persistent Cervical Carcinoma: A Gynecologic Oncology Group Study

From the University of California, Irvine, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Chao Family Comprehensive Cancer Center, Orange, CA; Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute; Department of Biostatistics, University at Buffalo, Buffalo, NY; University of Oklahoma, Oklahoma City, OK; The Ohio State University, Columbus, OH; M. D. Anderson Cancer Center, Houston, TX; Virginia Commonwealth University, Richmond, VA; University of Iowa, Iowa City, IA; Center on Outcomes, Research and Education, Evanston Northwestern Healthcare, Evanston; and Northwestern University Feinberg School of Medicine, Chicago, IL.

Corresponding author: Bradley J. Monk, MD, University of California, Irvine Medical Center, Building 56, Room 262, 101 The City Dr, Orange, CA 92868; e-mail: bjmonk{at}uci.edu.

Purpose Assess toxicity and efficacy of cisplatin (Cis) doublet combinations in advanced and recurrent cervical carcinoma.

Patients and Methods Patients were randomly assigned to paclitaxel 135 mg/m² over 24 hours plus Cis 50 mg/m² day 2 every 3 weeks (PC, reference arm); vinorelbine 30 mg/m² days 1 and 8 plus Cis 50 mg/m² day 1 every 3 weeks (VC); gemcitabine 1,000 mg/m² day 1 and 8 plus Cis 50 mg/m² day 1 every 3 weeks (GC); or topotecan 0.75 mg/m² days 1, 2, and 3 plus Cis 50 mg/m² day 1 every 3 weeks (TC). Survival was the primary end point with a 33% improvement relative to PC considered important (85% power, alpha = 5%). Quality-of-life data were prospectively collected.

Results A total of 513 patients were enrolled when a planned interim analysis recommended early closure for futility. The experimental-to-PC hazard ratios of death were 1.15 (95% CI, 0.79 to 1.67) for VC, 1.32 (95% CI, 0.91 to 1.92) for GC, and 1.26 (95% CI, 0.86 to 1.82) for TC. The hazard ratios for progression-free survival (PFS) were 1.36 (95% CI, 0.97 to 1.90) for VC, 1.39 (95% CI, 0.99 to 1.96) for GC, and 1.27 (95% CI, 0.90 to 1.78) for TC. Response rates (RRs) for PC, VC, GC, and TC were 29.1%, 25.9%, 22.3%, and 23.4%, respectively. The arms were comparable with respect to toxicity except for leucopenia, neutropenia, infection, and alopecia.

Conclusion VC, GC, and TC are not superior to PC in terms of overall survival (OS). However, the trend in RR, PFS, and OS favors PC. Differences in chemotherapy scheduling, pre-existing morbidity, and toxicity are important in individualizing therapy.

Supported by National Institutes of Health K-23 Grant No. CA 87558 (B.J.M.) and Grants No. CA 27469 to the Gynecologic Oncology Group (GOG) Administrative Office and CA 37517 to the GOG Statistical and Data Center from the National Cancer Institute.

Presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL.

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

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