Lookup NU author(s): Professor Ruth Plummer,
Professor Alan Boddy,
Dr Mark Verrill
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Purpose: To determine the recommended phase II dose of combination ixabepilone plus carboplatin based on the maximum tolerated dose, pharmacokinetics, optimum schedule, and safety. Experimental Design: Patients with advanced solid malignancies were treated with escalating doses of carboplatin plus ixabepilone administered on day 1 (schedule A) or days 1 and 8 (schedule B) of a 21-day cycle. Blood was sampled during cycle 1 for pharmacokinetic analysis of ixabepilone (both schedules) and carboplatin (schedule B). Results: Fifty-two patientswere treated with ixabepilone doses rangingfrom30to50mg/m2 per 21-day cycle plus carboplatin area under curve (AUC) 5 or 6 (Calvert formula). On schedule A (ixabepilone 40 mg/m 2 over 1 hour plus carboplatin (AUC 6), 2 of 2 patients experienced dose-limiting toxicity (DLT). On schedule B (ixabepilone 25 mg/m2 over 1 hour on days 1 and 8 plus carboplatin AUC 6), 3 of 3 patients experienced DLT. DLT was myelosuppression; however, cumulative sensory neuropathy limited extended dosing on schedule A. Ixabepilone and carboplatin pharmacokinetics were similar to those using either drug as monotherapy, indicating an absence of pharmacokinetic drug interactions. Based on DLTs and tolerability with repeated dosing, the recommended doses were 30 mg/m2 ixabepilone (1-hour infusion) d1 q3wplus carboplatin AUC 6 (schedule A) and 20 mg/m2 ixabepilone (1 hour infusion) d1, d8 q3wplus carboplatin AUC 6 (schedule B). Conclusions: Data from the present study showthe feasibility and tolerability of combination ixabepilone plus carboplatin, with ixabepilone administered on day 1 or on days 1 and 8 on a 21-day cycle. © 2008 American Association for Cancer Research.
Author(s): Plummer R, Woll P, Fyfe D, Boddy AV, Griffin M, Hewitt P, Carmichael J, Namouni F, Cohen M, Verrill M
Publication type: Article
Publication status: Published
Journal: Clinical Cancer Research
ISSN (print): 1078-0432
ISSN (electronic): 1557-3265
Publisher: American Association for Cancer Research
PubMed id: 19088046
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