Another Confirmation of the Inactivity of Topotecan in Ovarian Cancer

One decade ago, in an editorial in the Journal (1), I challenged investigators who were interested in improving outcomes to discontinue conducting multiple trials that addressed similar questions in the treatment of advanced ovarian carcinoma except when the purpose of such studies was to confirm possible practice-changing new treatment strategies. A negative report that appears in this issue (2) is the fifth study to investigate the addition of topotecan to the platinum and taxane backbone, the current standard of care for ovarian cancer that was confirmed here a decade ago (3). The authors even include a table in the article that demonstrates the accrual of 4451 patients to explore various permutations of the question: Does the addition of topotecan to a platinum and taxane backbone improve outcomes in patients with advanced ovarian carcinoma? The answer is a resounding “no” whether topotecan is used in a triplet (4), as part of a sequential doublet (2,5), or as consolidation (6,7). In the recently published trial by the Gynecologic Cancer Intergroup (5), 4321 ovarian cancer patients were accrued internationally from the United States, United Kingdom, Italy, Australia, and New Zealand. This five-arm study (GOG182/ICON5) explored the addition of topotecan, gemcitabine, or liposomal doxorubicin to the platinum and taxane backbone. None of the new agents improved any outcome measure, and each was more toxic in some fashion than the backbone alone. The accrual spanned the years 2001–2004. The current study (2) was developed during the same time period and accrued 819 patients from Canada, Spain, and several countries from the European Organization for Research and Treatment of Cancer between 2001 and 2005.