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01.02.2009 | Original Article

Phase I dose escalation study of weekly ixabepilone, an epothilone analog, in patients with advanced solid tumors who have failed standard therapy

verfasst von: Ahmad Awada, Martine J. Piccart, Suzanne F. Jones, Ronald A. Peck, Thierry Gil, David Lebwohl, Chi-Yuan Wu, Howard A. Burris III

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 3/2009

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Abstract

Purpose

To establish the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), safety and recommended Phase II dose of ixabepilone, administered weekly as an intravenous (IV) infusion to patients with solid tumors who have failed standard therapy.

Method

This was an open-label, single-arm, Phase I, dose-escalation study.

Results

The MTD of ixabepilone [30-min, weekly IV infusion on a 21-day schedule (N = 33)] was established at 25 mg/m². Grade 3 fatigue was the DLT in 2/4 patients treated at 30 mg/m². Ixabepilone was well tolerated at the MTD. Myelosuppression was rare, with no Grade 3/4 neutropenia. Due to the potential for cumulative neurotoxicity, the protocol was amended to a 1-h infusion, weekly for 3 weeks with a 1-week break. No DLT occurred at starting doses of 15, 20 and 25 mg/m² on this modified schedule (N = 51), although overall toxicity was less at 15 and 20 mg/m² than 25 mg/m². Five patients (2 on the 30-min/21-day schedule and 3 on the 60-min/28-day schedule) achieved durable objective partial responses across a variety of tumor types.

Conclusions

Ixabepilone had an acceptable safety profile at the MTD of 25 mg/m² (as a 30-min weekly infusion on a continuous 21-day schedule) and at 20 mg/m² (as a 1-h weekly infusion on a modified 28-day schedule). The clinical activity and acceptable tolerability profile warrant further single- or combination-agent evaluation.

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Titel: Phase I dose escalation study of weekly ixabepilone, an epothilone analog, in patients with advanced solid tumors who have failed standard therapy
verfasst von: Ahmad Awada
Martine J. Piccart
Suzanne F. Jones
Ronald A. Peck
Thierry Gil
David Lebwohl
Chi-Yuan Wu
Howard A. Burris III
Publikationsdatum: 01.02.2009
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 3/2009
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-008-0751-5

Springer Medizin

Phase I dose escalation study of weekly ixabepilone, an epothilone analog, in patients with advanced solid tumors who have failed standard therapy