title: 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.
abstract: 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/m(2)/day x 5 days every 21 days (arm A) or 20 mg/m(2) 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/m(2) 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.
authors.affiliation: Department of Medical Oncology, Division of Medical Sciences, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA. barbara.burtness@fccc.edu
authors.forename: B A
authors.initials: BA
authors.lastname: Burtness
authors.forename: J
authors.initials: J
authors.lastname: Manola
authors.forename: R
authors.initials: R
authors.lastname: Axelrod
authors.forename: A
authors.initials: A
authors.lastname: Argiris
authors.forename: A A
authors.initials: AA
authors.lastname: Forastiere
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000556:secondary / Q000628:therapy; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D000077143:Docetaxel; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D034261:Epothilones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000628:therapy; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D012008:Recurrence; D016879:Salvage Therapy; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D000903:Antibiotics, Antineoplastic; D034261:Epothilones; D043823:Taxoids; D000077143:Docetaxel; C430592:ixabepilone; D017239:Paclitaxel