Annals of Oncology Advance Access originally published online on February 21, 2008
Annals of Oncology 2008 19(5):977-983; doi:10.1093/annonc/mdm591
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head and neck cancer |
A randomized phase II study of ixabepilone (BMS-247550) given daily x 5 days every 3 weeks or weekly in patients with metastatic or recurrent squamous cell cancer of the head and neck: an Eastern Cooperative Oncology Group study
1 Department of Medical Oncology, Division of Medical Sciences, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111
2 Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA
3 Department of Medicine, Thomas Jefferson University, Philadelphia, PA
4 Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh, Pittsburgh, PA
5 Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD, USA
* Correspondence to: Dr B. Burtness, Department of Medical Oncology, Division of Medical Sciences, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA. Tel: +1-215-728-3023; Fax: +1-215-728-3639; E-mail: barbara.burtness{at}fccc.edu
Ixabepilone is a tubulin-polymerizing agent with potential activity in squamous cell carcinoma of the head and neck (SCCHN). Patients were eligible who had incurable, measurable SCCHN and less than two prior regimens for metastatic/recurrent disease. Eastern Cooperative Oncology Group performance status of less than or equal to one and adequate renal/hepatic/hematological function were required. Patients were randomly assigned to receive ixabepilone 6 mg/m2/day x 5 days every 21 days (arm A) or 20 mg/m2 on days 1, 8, and 15 of a 28-day cycle (arm B). Each arm accrued taxane-naive and -exposed strata in a two-stage design. The primary end point was response. Eighty-five eligible patients entered; there was one response in a taxane-exposed patient among 32 patients on arm A. Five of 35 taxane-naive patients on arm B had partial responses (14%). No taxane-exposed patient on arm B responded. Common grades 3 and 4 toxic effects were fatigue, neutropenia, and sensory/motor neuropathy. Median survival for arm A taxane-naive and taxane-exposed patients is 5.6 and 6.5 months; for arm B, taxane-naive and taxane-exposed patients is 7.8 and 6.5 months. Weekly ixabepilone 20 mg/m2 is active in taxane-naive patients with SCCHN. A high incidence of motor and sensory grade 3 neuropathy resulted at this dose and schedule. Further development of ixabepilone in previously treated head and neck cancer is not warranted on the basis of these data.
Key words: antimicrotubule therapy, epothilone, squamous cell carcinoma of the head and neck
Received for publication July 12, 2007. Revision received December 7, 2007. Accepted for publication December 10, 2007.