Lee Christopher W, Bélanger Karl, Rao Sanjay C, Petrella Teresa M, Tozer Richard G, Wood Lori, Savage Kerry J, Eisenhauer Elizabeth A, Synold Timothy W, Wainman Nancy, Seymour Lesley
BC Cancer Agency - Fraser Valley Centre, 13750 96th Avenue, Surrey, BC, Canada V3V 1Z2.
Invest New Drugs. 2008 Jun;26(3):249-55. doi: 10.1007/s10637-007-9097-9. Epub 2007 Oct 26.
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.
评估驱动蛋白纺锤体蛋白（KSP）抑制剂ispiensib对恶性黑色素瘤的缓解率和毒性。2005年4月至11月共纳入17例患者。Ispinesib以18mg/m²的剂量静脉输注1小时，每3周给药1次，直至疾病进展。未观察到客观缓解。6例患者（35%）的最佳反应为疾病稳定，中位持续时间为2.8个月。9例（53%）患者在1或2个周期后出现疾病进展。88%的患者接受了≥90%的计划剂量强度。3级非血液学毒性包括头晕（1例）和视力模糊（1例）。有1例发热性中性粒细胞减少症，但无3级或4级生化不良事件。药代动力学与先前研究一致。16份可用存档组织样本中有14份（88%）检测到KSP免疫反应性。按照所采用的剂量和给药方案，Ispinesib可以安全给药，血液学和非血液学毒性均较轻。未观察到客观缓解，不建议在恶性黑色素瘤中进一步开发单药Ispinesib。虽然KSP表达在黑色素瘤中似乎很常见，但KSP可能不是其治疗的合适靶点。
