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Lookup NU author(s): Professor Alan Boddy, Huw ThomasORCiD, Lynsey Robson, Professor Alan Calvert
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The aim of this phase I study was to determine the maximum tolerated dose of a 3-h infusion of paclitaxel, combined with carboplatin at a fixed AUC of 7 mg ml-1 min every 4 weeks for up to six cycles and to evaluate any possible pharmacokinetic interaction. Twelve chemonaive patients with ovarian cancer were treated with paclitaxel followed by a 30-min infusion of carboplatin. Paclitaxel dose was escalated from 150 mg m-2 to 225 mg m-2 in cohorts of three patients. Carboplatin dose was based on renal function, Pharmacokinetic studies were performed in nine patients (at least two at each dose level). A total of 66 courses were evaluable for assessment. Grade 3 or 4 neutropenia was seen in 70% of the courses, however hospitalization was not required. Grade 3 or 4 thrombocytopenia occurred in 24% of the courses. Alopecia, myalgia and peripheral neuropathy were common but rarely severe. The pharmacokinetics of paclitaxel was non-linear and did not appear to be influenced by co-administration of carboplatin. The AUC of carboplatin was 7.0 ± 1.4 mg ml-1 min, indicating that there was no pharmacokinetic interaction. The combination of carboplatin and paclitaxel may be administered as first-line treatment for advanced ovarian cancer. Although myelosuppression is the dose-limiting toxicity of the component drugs, the severity of thrombocytopenia was less than anticipated. The results of this study, with only a small number of patients, need to be confirmed in future investigations.
Author(s): Siddiqui N, Boddy AV, Thomas HD, Bailey N, Robson L, Lind M, Calvert AH
Publication type: Article
Publication status: Published
Journal: British Journal of Cancer
Year: 1997
Volume: 75
Issue: 2
Pages: 287-294
Print publication date: 01/01/1997
ISSN (print): 0007-0920
ISSN (electronic):
URL: http://cat.inist.fr/?aModele=afficheN&cpsidt=2554588
PubMed id: 9010040