title: A phase II study of ispinesib (SB-715992) in patients with metastatic or recurrent malignant melanoma: a National Cancer Institute of Canada Clinical Trials Group trial.
abstract: To assess the response rate and toxicity of the kinesin spindle protein (KSP) inhibitor, ispinesib, in malignant melanoma. Seventeen patients were enrolled from April to November 2005. Ispinesib was administered as a 1-hour infusion at a dose of 18 mg/m2 once every 3 weeks until disease progression. No objective responses were seen. Six patients (35%) had a best response of stable disease for a median duration of 2.8 months. Disease progression was documented in 9 (53%) after 1 or 2 cycles. Eighty-eight percent of patients received > or =90% of planned dose intensity. Grade 3 non-hematologic toxicities included dizziness (1) and blurred vision (1). There was one episode of febrile neutropenia, but no grade 3 or 4 biochemical adverse events. Pharmacokinetics was consistent with prior studies. KSP immunoreactivity was seen in 14 of 16 available archival tissue samples (88%). Ispinesib can be safely administered using the dose and schedule employed, with mild hematologic and non-hematologic toxicity. No objective responses were observed, and further development of single-agent ispinesib in malignant melanoma is not recommended. Although KSP expression appears to be common in melanoma, KSP may not be a suitable target for its treatment.
authors.affiliation: BC Cancer Agency - Fraser Valley Centre, 13750 96th Avenue, Surrey, BC, Canada V3V 1Z2. clee@bccancer.bc.ca
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Lee
authors.forename: Karl
authors.initials: K
authors.lastname: Bélanger
authors.forename: Sanjay C
authors.initials: SC
authors.lastname: Rao
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Petrella
authors.forename: Richard G
authors.initials: RG
authors.lastname: Tozer
authors.forename: Lori
authors.initials: L
authors.lastname: Wood
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Savage
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Eisenhauer
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Synold
authors.forename: Nancy
authors.initials: N
authors.lastname: Wainman
authors.forename: Lesley
authors.initials: L
authors.lastname: Seymour
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001549:Benzamides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018450:Disease Progression; D016503:Drug Delivery Systems; D005134:Eye Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D016547:Kinesins / Q000037:antagonists & inhibitors; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D009092:Mucous Membrane / Q000187:drug effects / Q000473:pathology; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011799:Quinazolines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; C470243:KIF11 protein, human; D011799:Quinazolines; C508757:ispinesib; D016547:Kinesins