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A phase I/II trial and pharmacokinetic study of ixabepilone in adult patients with recurrent high-grade gliomas

  • Clinical Study – Patient Study
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An Erratum to this article was published on 01 June 2010

Abstract

Ixabepilone is an epothilone, a novel class of non-taxane microtubule stabilizing agents. A phase I/II and pharmacokinetic trial of ixabepilone was conducted in patients with recurrent high-grade gliomas. Adult patients received ixabepilone as a 1-h infusion daily for 5 days every 3 weeks. A modified continual reassessment method was used to escalate doses, beginning at 5.0 mg/m2, in patients stratified by use or non-use of enzyme inducing antiepileptic drugs (EIAED). In the phase I study, the maximum tolerated dose (MTD) and pharmacokinetics of ixabepilone were determined for each group. The phase II study used a two-stage design to evaluate response rate. Secondary endpoints were survival and 6-month progression free survival. In the phase I trial, 38 patients (median age 54 years) were enrolled. The MTD was 6.8 mg/m2 for patients not taking EIAEDs and 9.6 mg/m2 for those taking EIAEDs. The dose limiting toxicities in both groups were hematologic. Twenty-three patients (median age 54 years) were enrolled in the first stage of the phase II trial. No objective responses were observed. Median overall survival was 5.8 (95% CI, 5.0–8.6) months and 6-month PFS rate was 4% (95% CI, 0–22%). The overall mean total body clearance for ixabepilone was significantly higher (P = 0.003) in patients receiving EIAEDs (36 ± 11 l/h/m2) than those not (24 ± 9.2 l/h/m2). Patients on EIAEDs had a substantially higher MTD likely due to induction of cytochrome P450. Ixabepilone had no activity in patients with recurrent high-grade gliomas.

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Acknowledgments

This study was performed by the New Approaches to Brain Tumor Therapy CNS Consortium, Baltimore, MD, USA, and supported in part by National Cancer Institute UO1 Grant CA62475 (NABTT Central Office). Kathryn A. Carson’s work on the manuscript was supported by National Center for Research Resources grant UL1 RR 025005. We are grateful to Kimberly Busby for her support of this clinical trial development and manuscript.

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Authors and Affiliations

  1. Cleveland Clinic Brain Tumor and Neuro-Oncology Center, Cleveland, OH, USA

    David M. Peereboom

  2. Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Jeffrey G. Supko, Tracy Batchelor & Xiaoying He

  3. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Kathryn A. Carson

  4. Cedar Sinai Medical Center, Los Angeles, CA, USA

    Surasak Phuphanich

  5. Wake Forest University, Winston-Salem, NC, USA

    Glenn Lesser

  6. Henry Ford Hospital, Detroit, MI, USA

    Tom Mikkelson

  7. The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Cancer Research Building 2, Room 1M15, 1550 Orleans Street, Baltimore, MD, 21231, USA

    Joy Fisher, Serena Desideri & Stuart A. Grossman

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  1. David M. Peereboom
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  2. Jeffrey G. Supko
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  3. Kathryn A. Carson
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  8. Joy Fisher
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The New Approaches to Brain Tumor Therapy (NABTT) Consortium

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Correspondence to Joy Fisher.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s11060-010-0234-5

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Peereboom, D.M., Supko, J.G., Carson, K.A. et al. A phase I/II trial and pharmacokinetic study of ixabepilone in adult patients with recurrent high-grade gliomas. J Neurooncol 100, 261–268 (2010). https://doi.org/10.1007/s11060-010-0190-0

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  • DOI: https://doi.org/10.1007/s11060-010-0190-0

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