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. 2008 Jun;26(3):249-55. doi: 10.1007/s10637-007-9097-9. Epub 2007 Oct 26.

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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Benzamides / adverse effects
  • Benzamides / pharmacokinetics
  • Benzamides / therapeutic use*
  • Disease Progression
  • Drug Delivery Systems
  • Eye Neoplasms / drug therapy*
  • Female
  • Humans
  • Kinesin / antagonists & inhibitors
  • Male
  • Melanoma / drug therapy*
  • Middle Aged
  • Mucous Membrane / drug effects
  • Mucous Membrane / pathology
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local
  • Quinazolines / adverse effects
  • Quinazolines / pharmacokinetics
  • Quinazolines / therapeutic use*
  • Skin Neoplasms / drug therapy*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Benzamides
  • KIF11 protein, human
  • Quinazolines
  • ispinesib
  • Kinesin