A Phase II Study of Docetaxel in Paclitaxel-Resistant Ovarian and Peritoneal Carcinoma
Abstract & Commentary
Synopsis: Docetaxel is active in paclitaxel-resistant ovarian and peritoneal cancer, but, in view of significant hematologic toxicity, further study is warranted to ascertain its optimal dose and schedule.
Source: Rose PG, et al. Gynecol Oncol. 2003;88: 130-135.
Within the Gynecologic Oncology Group, Rose and colleagues conducted this phase II study of a relatively new drug, docetaxel, which is a taxane agent (related to paclitaxel [Taxol]) that is an inhibitor of microtubule depolymerization and has demonstrated activity in paclitaxel-resistant breast cancer and gynecologic cancer. Sixty patients were entered and treated with a total of 256 courses, with all 50 evaluable for toxicity and 58 evaluable for response. Responses were observed in 22.4% of patients, with 5.2% achieving complete response and 17.2% achieving partial response. The median duration of response was 2.5 months. The likelihood of observing a response did not appear to be related to the length of the prior paclitaxel-free interval or duration of prior paclitaxel infusions. The principal adverse effect of grade 4 neutropenia occurred in 75% of patients. There was 1 treatment-related death. Dose reductions were required in 36% of patients. Rose et al concluded that docetaxel is active in paclitaxel-resistant ovarian and peritoneal cancer but also indicated that, in view of significant hematologic toxicity, further study is warranted to ascertain its optimal dose and schedule.
Comment by David M. Gershenson, MD
Like paclitaxel (Taxol®), docetaxel is a taxane drug that has activity against epithelial ovarian cancer. Randomized phase III trials have demonstrated that the combination of docetaxel + carboplatin has efficacy equivalent to the combination of paclitaxel + carboplatin in patients with newly diagnosed advanced epithelial ovarian cancer. Importantly, docetaxel has considerably less associated neurotoxicity than paclitaxel but more myelotoxicity. Docetaxel is being used increasingly in the first-line setting in combination with carboplatin, and it is also being used more commonly in the recurrent setting. In general, most oncologists have preliminarily considered docetaxel and paclitaxel to be interchangeable in terms of activity. Similarly, if a patient has demonstrated tumor resistance to one of the taxane agents, it has been thought that resistance to the other taxane is likely (cross-resistance). In fact, this study demonstrates that there is not complete cross-resistance, since 22.4% of all patients with paclitaxel-resistant ovarian and peritoneal cancer who received docetaxel responded. As expected, neutropenia was the most bothersome side effect, but the starting dose of docetaxel in this study was 100 mg/m2. Lower doses can ameliorate this toxicity. As Rose et al correctly note, the findings of this study clearly expand our armamentarium against ovarian cancer, but future studies will be required to establish the optimal dose and schedule for this interesting agent.
Dr. Gershenson is Professor and Chairman, Department of Gynecology, M.D. Anderson Cancer Center, Houston, Tex.