European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: high-dose versus low-dose and long versus short infusion.

Taxol (paclitaxel; Bristol-Myers Squibb, Wallingford, CT) is a new anticancer agent with activity in a number of human tumors, including epithelial ovarian cancer. In nonrandomized trials, doses studied have ranged from 135 mg/m2 to 250 mg/m2 administered over 24 hours with premedication to avoid hypersensitivity reactions (HSRs). This study addressed two questions: the dose-response relationship of Taxol in relapsed ovarian cancer and the safety of a short infusion given with premedication.
Women with platinum-pretreated epithelial ovarian cancer and measurable recurrent disease were randomized in a bifactorial design to receive either 175 or 135 mg/m2 of Taxol over either 24 or 3 hours. Major end points were the frequency of significant HSRs and objective response rate. Secondary end points were progression-free and overall survival.
Of 407 patients randomized, 391 were eligible and 382 assessable for response. Analysis was performed according to the bifactorial design. Severe HSRs were rare (1.5% patients) and were not affected by either dose or schedule. Response was slightly higher at the 175-mg/m2 dose (20%) than at 135 mg/m2 (15%), but this was not statistically significant (P = .2). However, progression-free survival was significantly longer in the high-dose group (19 v 14 weeks; P = .02). Significantly more neutropenia was seen when Taxol was administered as a 24-hour infusion. Response rates were similar in the 24- and 3-hour groups (19% and 16%, respectively; P = .6). No survival differences were noted.
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 progression at 175 mg/m2. The observation that longer infusion produces more myelosuppression but does not yield higher response rates should lead to further studies to determine the optimal dose and schedule of this interesting new agent.
AuthorsE A Eisenhauer, W W ten Bokkel Huinink, K D Swenerton, L Gianni, J Myles, M E van der Burg, I Kerr, J B Vermorken, K Buser, N Colombo
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 12 Issue 12 Pg. 2654-66 (Dec 1994) ISSN: 0732-183X [Print] UNITED STATES
PMID7989941 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Paclitaxel
  • Adult
  • Aged
  • Canada
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Europe
  • Female
  • Humans
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local (drug therapy, mortality)
  • Ovarian Neoplasms (drug therapy, mortality)
  • Paclitaxel (administration & dosage, adverse effects, pharmacokinetics)
  • Premedication
  • Quality of Life
  • Remission Induction
  • Survival Analysis
  • Treatment Outcome

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