Intravenous chemotherapy for ovarian cancer - the state of the art?
In 1999, two cytotoxic drug classes have emerged as essential components of intravenous chemotherapy for advanced ovarian cancer: the taxoids and the platinum compounds. Two large-scale randomized trials were required to convince most oncologists (and health care purchasers) that the combination of paclitaxel and cisplatin could be considered as standard therapy. Remarkably, the survival advantage achieved over treatment with cyclophosphamide and cisplatin (approximately 12 months) was virtually the same in the two trials (one in the USA, one an international Intergroup), despite differences in trial design. While these trials were proceeding, others continued to examine the role of carboplatin, and an overview by meta-analysis suggests this compound has equal efficacy as cisplatin at appropriate doses, but with much less toxicity. A paclitaxel-carboplatin regimen therefore has been widely adopted, particularly as this combination demonstrates the intriguing phenomenon of platelet-sparing, allowing full doses of both agents to be given. Preliminary results from three trials indicate equivalence between this combination and paclitaxel-cisplatin, with clear benefits in terms of toxicity, although mature survival data are not yet available. Many unanswered questions remain regarding intravenous chemotherapy. These include optimal duration (particularly for a taxoid) and the potential benefit for the addition of a third agent, either an established agent, such as an anthracycline or etoposide, or a newer agent, such as topotecan or gemcitabine. Three drug combinations may lead to innovative trial designs; a promising candidate might be sequential therapy. For the two lead drugs, other schedules, eg, a sequential approach, merit assessment, and alternative agents such as docetaxel and oxaliplatin also provide intriguing preclinical and early clinical data. Thus the stage is set for a number of interesting trials in the coming years.
CRC Department of Medical Oncology, University of Glasgow, CRC Beatson Laboratories and, Beatson Oncology Center, Western Infirmary, Glasgow, Scotland, UK.
S. B.
SB
Kaye