Clinical trials of newer regimens for treating ovarian cancer: the rationale for Gynecologic Oncology Group Protocol GOG 182-ICON5

Objectives. The current standard of chemotherapy for previously untreated patients with stage III/IV ovarian cancer who have undergone optimal or suboptimal cytoreductive surgery leaves room for improvement in terms of response rate and both progression-free and overall survival. Gynecologic Oncology Group (GOG) 182-ICON5 is a five-arm international collaborative study designed to improve on the efficacy of standard platinum/taxane therapy by incorporating newer cytotoxic agents in sequential doublet and triplet combinations. Methods. The evolution of a standard regimen for treating advanced ovarian cancer is reviewed, and the reasons for selecting carboplatin and paclitaxel for the control arm of the study are presented. Among the newer agents available for the experimental treatment arms, three stood out-gemcitabine, polyethylene-glycol (PEG)-liposomal doxorubicin, and topotecan-based on evidence of their activity demonstrated in previous phase I and II trials and, with appropriate dosage modifications, manageable toxicity when used in combination with platinum. Results. GOG 182-ICON5 is now in its second year of accrual. Patient recruitment, which is anticipated to grow to between 3400 and 4000 patients by the time the study is closed, is meeting expectations, and no problems have been encountered, except for the initial slow pace of recruitment outside of the United States. Conclusions. Combination chemotherapy using newer cytotoxic agents with demonstrated activity in treating advanced-stage ovarian cancer and the ability to enhance platinum-based therapies appears to offer hope of prolonging life and reducing mortality from this disease. 0 2003 Elsevier Inc. All rights reserved.