Activity of Anthracyclines in Refractory Ovarian Cancer: Recent Experience and Review

First-line approaches against epithelial ovarian cancer have undergone considerable evolution in the last two decades. Doxorubicin (Adriamycin) was initially used as part of polychemotherapy regimens combined with alkylating agents. Subsequently, the activity of cisplatin and efforts to maximize its dose intensity, together with randomized trials (1), led to questioning the importance of doxorubicin in these combinations. The chemotherapy of choice, therefore, became cisplatin-based regimens, usually in combination with cyclophosphamide. More recently paclitaxel showed major activity in platinum-refractory disease (2) and became incorporated into a combination with cisplatin. Following a randomized trial by the Gynecologic Oncology Group (GOG), the combination of paclitaxel and cisplatin is now considered the initial chemotherapy of choice for stage III and IV ovarian cancer (3). However, a number of studies and meta-analysis lend support for a positive contribution of anthracyclines in the treatment of ovarian cancer. Our recent experience with a liposomal doxorubicin formulation (Doxil) is a further indication of activity by this class of drugs in the management of this disease. This favorable experience raises renewed questions as to the role of anthracyclines in ovarian cancer and suggests a lack of cross-resistance to paclitaxel, which has also been observed in breast cancer (4). We review the potential for anthracyclines in this refractory setting and report the responses during a phase I trial of Doxil. A phase II study has recently been completed and reported elsewhere (4a).