Carboplatin/Paclitaxel Induction in Ovarian Cancer: The Finer Points

The carboplatin/paclitaxel doublet remains the chemotherapy backbone for the initial treatment of ovarian cancer. This two-drug regimen, with carboplatin dosed using the Calvert formula, yielded convincing noninferior outcomes when compared with the prior, more toxic, regimen of cisplatin/paclitaxel. Carboplatin's dose-limiting toxicity is thrombocytopenia; however, when this drug is properly dosed and combined with paclitaxel, the doublet's cycle 1 dose in chemotherapy-naive women is generally safe. Carboplatin (unlike cisplatin) contributes minimally to the cumulative sensory neuropathy of paclitaxel, thus ensuring noticeable reversibility of neuropathy symptoms following completion of 6 cycles and only occasionally requiring cessation or substitution of the taxane. Paclitaxel is responsible for the hair loss associated with the carboplatin/paclitaxel doublet; preventive measures must be considered for patients who would otherwise refuse treatment. Several first-line phase III trials, as well as ongoing trials for which only preliminary results have been published, have fueled debates on the optimal dose and schedule; these have focused not only on weekly vs q3-weeks paclitaxel, but also on other modifications and the advisability of adding bevacizumab. Our view is that results of this doublet in the first-line treatment of ovarian cancer are driven primarily by carboplatin, given that ovarian cancer is a platinum-sensitive disease. Consequently, the roles of the accompanying paclitaxel dose and schedule and the addition of bevacizumab are currently unsettled, and questions regarding these issues should be decided based on patient tolerance and comorbidities until additional data are available.