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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

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Summary

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 ≥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.

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Authors and Affiliations

  1. BC Cancer Agency - Fraser Valley Centre, 13750 96th Avenue, Surrey, BC, Canada, V3V 1Z2

    Christopher W. Lee

  2. Centre Hospitalier de l’Université de Montréal, Hôpital Notre-Dame, 1560 Sherbrooke Street East, Montreal, QC, Canada, H2L 4M1

    Karl Bélanger

  3. BC Cancer Agency - Centre for the Southern Interior, 399 Royal Avenue, Kelowna, BC, Canada, V1Y 5L3

    Sanjay C. Rao

  4. Odette Cancer Centre, 2075 Bayview Avenue, Toronto, ON, Canada, M4N 3M5

    Teresa M. Petrella

  5. Juravinski Cancer Centre, 699 Concession Street, Hamilton, ON, Canada, L8V 5C2

    Richard G. Tozer

  6. Queen Elizabeth II Health Sciences Centre, 1278 Tower Road, 4th Floor Bethune Building, Halifax, NS, Canada, B3H 2Y9

    Lori Wood

  7. BC Cancer Agency - Vancouver Centre, 600 West 10th Avenue, Vancouver, BC, Canada, V5Z 4E6

    Kerry J. Savage

  8. National Cancer Institute of Canada Clinical Trials Group, Queen’s University, 10 Stuart Street, Kingston, ON, Canada, K7L 3N6

    Elizabeth A. Eisenhauer, Nancy Wainman & Lesley Seymour

  9. City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA, 91010, USA

    Timothy W. Synold

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  1. Christopher W. Lee
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  2. Karl Bélanger
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Correspondence to Christopher W. Lee.

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Lee, C.W., Bélanger, K., Rao, S.C. et al. 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. Invest New Drugs 26, 249–255 (2008). https://doi.org/10.1007/s10637-007-9097-9

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  • DOI: https://doi.org/10.1007/s10637-007-9097-9

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