EUROPEAN-CANADIAN RANDOMIZED TRIAL OF PACLITAXEL IN RELAPSED OVARIAN-CANCER - HIGH-DOSE VERSUS LOW-DOSE AND LONG VERSUS SHORT INFUSION

Purpose: Taxol (paclitaxel; Bristol-Myers Squibb, Wallingford, CT) is a new anticancer agent with activity in a number of human tumors, incl uding epithelial ovarian cancer. In nonrandomized trials, doses studie d have ranged from 135 mg/m(2) to 250 mg/m(2) administered over 24 hou rs with premedication to avoid hypersensitivity reactions (HSRs). This study addressed two questions: the dose-response relationship of Taxo l in relapsed ovarian cancer and the safety of a short infusion given with premedication. Methods: Women with platinum-pretreated epithelial ovarian cancer and measurable recurrent disease were randomized in ct bifactorial design to receive either 175 or 135 mg/m(2) of Taxol over either 24 or 3 hours. Major end points were the frequency of signific ant HSRs and objective response rate. Secondary end points were progre ssion-free and overall survival. Results: Of 407 patients randomized, 391 were eligible and 382 assessable for response. Analysis was perfor med according to the bifactorial design. Severe HSRs were rare (1.5% p atients) and were not affected by either dose or schedule. Response wa s slightly higher at the 175-mg/m(2) dose (20%) than at 135 mg/m(2) (1 5%), but this was not statistically significant (P = .2). However, pro gression-free survival was significantly longer in the high-dose group (19 v 14 weeks; P = .02). Significantly more neutropenia was seen whe n Taxol was administered as a 24-hour infusion. Response rates were si milar in the 24- and 3-hour groups (19% and 16%, respectively; P = .6) . No survival differences were noted. Conclusion: The 3-hour infusion of Taxol is safe when given with premedication and is associated with less neutropenia. There is a modest dose effect with longer time to pr ogression at 175 mg/m(2). The observation that longer infusion produce s more myelosuppression but does not yield higher response rates shoul d lead to further studies to determine the optimal dose and schedule o f this interesting new agent.