Relevance of chemotherapy dose and schedule to outcomes in ovarian cancer

Abstract

The current standard of care in ovarian cancer is complete surgical cytoreduction followed by adjuvant (postoperative) platinum-based chemotherapy. Taxanes are frequently combined with platinum compounds in the adjuvant chemotherapy setting and, whether they are given in combination or sequentially, they produce greater progression-free and overall survival than historical combination regimens. Because the treatment of ovarian cancer relies on chemotherapy, this article reviews the evidence for a correlation between chemotherapy delivered at full dose on schedule (FDOS) and patient outcomes. Meta-analyses have suggested that the dose intensities of cisplatin and carboplatin correlate with survival. However, the findings in these hypothesis-generating analyses have not been confirmed in prospective trials. In addition, increasing the dose of cisplatin above a certain threshold is not recommended in ovarian cancer because of the greater toxicity with higher doses of platinum compounds. The delivered dose intensities of taxanes used as single agents have not been shown to correlate with patient outcomes, but adding a taxane to platinum compounds appears both to attenuate the toxicity of the platinum compounds and to facilitate the delivery of FDOS chemotherapy. In the literature on ovarian cancer there is no clear consensus on the benefit of maintaining FDOS chemotherapy. Clinical studies, especially a proposed trial of a dose-dense carboplatin and paclitaxel combination, may provide stronger evidence for the effect of FDOS chemotherapy in ovarian cancer.