A phase i study of ixabepilone in combination with epirubicin in patients with metastatic breast cancer

Henri Roché, Elena De Benedictis, Ewa Cottura, Silvia Govi, Florence Dalenc, Alberta Locatelli, Marion Deslandres, Milvia Zambetti, Laurence Gladieff, Marianne Messina, Luca Gianni

Research output: Contribution to journalArticle

Abstract

Purpose: The objectives of this phase I trial were to determine the maximum-tolerated dose (MTD), toxicity profile, dose-limiting toxicities (DLT), pharmacokinetics, and the recommended phase II dose for ixabepilone in combination with epirubicin in women with metastatic breast cancer. Patients and Methods: Patients 2) and escalating doses of ixabepilone (25, 30, and 35 mg/m2). Results: Forty-two women were treated at 3 different dose levels of ixabepilone: 25 (n = 6), 30 (n = 30), and 35 mg/m2 (n = 6) in combination with 75 mg/m2 epirubicin. The MTD of ixabepilone in combination with epirubicin 75 mg/m2 was 30 mg/m2, and the DLT dose was 35 mg/m2 with grade 4 neutropenia. Grade 3/4 neutropenia was the most frequent moderate-to-severe adverse event and was manageable and reversible. No deaths were reported. Objective responses were achieved in 18 of 32 patients with measurable disease (56% [90% CI, 40%-71%]) and in 9 of 22 evaluable patients treated at the MTD (41% [90% CI, 23%-61%]). Ixabepilone clearance and the epirubicin pharmacokinetic profile were similar across ixabepilone dose levels. Conclusions: The combination of ixabepilone and epirubicin was clinically active. The recommended dose for evaluation in phase II is epirubicin 75 mg/m2, followed by ixabepilone 30 mg/m 2 every 3 weeks.

Original languageEnglish
Pages (from-to)167-174
Number of pages8
JournalClinical Breast Cancer
Volume12
Issue number3
DOIs
Publication statusPublished - 2012

Keywords

  • Anthracycline
  • Epirubicin
  • Ixabepilone
  • Metastatic breast cancer
  • Taxane

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Roché, H., De Benedictis, E., Cottura, E., Govi, S., Dalenc, F., Locatelli, A., Deslandres, M., Zambetti, M., Gladieff, L., Messina, M., & Gianni, L. (2012). A phase i study of ixabepilone in combination with epirubicin in patients with metastatic breast cancer. Clinical Breast Cancer, 12(3), 167-174. https://doi.org/10.1016/j.clbc.2012.03.009