Maintenance Therapy for Ovarian Cancer: Of Helsinki and Hippocrates

In this issue of Journal of Clinical Oncology (JCO), an Italian consortium presents the results of a randomized, phase III trial 1 in ovarian cancer that addresses the potential value of continued therapy (ie, maintenance therapy) after attainment of a clinical or pathologic complete response to primary treatment. They conclude that six additional every-3-week cycles of paclitaxel monotherapy do not alter the important end points of progression-free or overall survival. Though there are some criticisms that can be leveled at the conduct of the trial, the negative results are not surprising in the context of the preponderance of data in ovarian cancer-as well as in other solid tumors-that fail to show convincingly that such a strategy is effective. One fault with this study is that 15% of patients in the control arm received some maintenance paclitaxel, 6% of the patients in the maintenance arm received no paclitaxel, and an additional 3% in the maintenance arm discontinued therapy early because of withdrawal of consent. However, in both the intent-to-treat analysis and the perprotocol analysis, no differences emerged in outcomes as a function of providing or withholding maintenance therapy. These data are in concert with multiple negative studies that have used the phase III, randomized trial design to test high-dose chemotherapy with stemcell rescue, intravenous topotecan, intravenous epirubicin, intravenous monoclonal antibody directed at CA-125 (ie, oregovomab), subcutaneous interferon alfa, intraperitoneal yttrium-90 -labeled monoclonal antibody directed against the MUC-1 antigen, intraperitoneal phosphorus-32 chromic phosphate, and whole-abdomen radiation therapy. In every instance, additional treatment has failed to alter progression or survival in patients who have no clinical evidence of disease after standard therapy with surgery and chemotherapy. These studies are referenced in the article by Pecorelli et al 1 in this issue of JCO for those readers unfamiliar with the specifics of each study.