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.
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.
Lee
Christopher W
CW
BC Cancer Agency - Fraser Valley Centre, 13750 96th Avenue, Surrey, BC, Canada V3V 1Z2. clee@bccancer.bc.ca
Bélanger
Karl
K
Rao
Sanjay C
SC
Petrella
Teresa M
TM
Tozer
Richard G
RG
Wood
Lori
L
Savage
Kerry J
KJ
Eisenhauer
Elizabeth A
EA
Synold
Timothy W
TW
Wainman
Nancy
N
Seymour
Lesley
L
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
D000970:Antineoplastic Agents; D001549:Benzamides; C470243:KIF11 protein, human; D011799:Quinazolines; C508757:ispinesib; D016547:Kinesins