Lee Richard T, Beekman Kathleen E, Hussain Maha, Davis Nancy B, Clark Joseph I, Thomas Sachdev P, Nichols Katherine F, Stadler Walter M
Department of Medicine, Section of Hematology/Oncology, The University of Chicago, IL 60637, USA.
Clin Genitourin Cancer. 2008 Mar;6(1):21-4. doi: 10.3816/CGC.2008.n.003.
Advanced renal cell cancer (RCC) continues to have a poor overall prognosis despite new FDA-approved therapies. Although taxane-based therapies are generally ineffective in RCC, research into the role of the von Hippel-Lindau protein has shown an association with microtubule dynamics. Mitotic kinesins are a class of molecular motors that also interact with microtubules and are required for proper mitotic function. SB-715992 is a new agent that inhibits the function of a mitotic kinesin known as kinesin spindle protein and leads to cell death.
Twenty patients with previously treated advanced RCC were enrolled on this phase II trial of SB-715992, with response rate as a primary endpoint.
No patients responded with complete or partial remission. Six patients had stable disease, and 1 patient continues on therapy after 12 cycles. Common toxicities included anemia (80%), elevated creatinine (70%), lymphopenia (45%), fatigue (50%), hyperglycemia (50%), and dyspnea (45%). Reported grade 3/4 toxicities included dyspnea, fatigue, neutropenia with skin infection, dizziness, hyperuricemia, and hypertension.
This dose and schedule of SB-715992 does not appear to have a significant cytotoxic effect for patients with previously treated advanced RCC.
尽管有美国食品药品监督管理局（FDA）批准的新疗法，晚期肾细胞癌（RCC）的总体预后仍然较差。虽然基于紫杉烷的疗法在RCC中通常无效，但对冯·希佩尔-林道蛋白作用的研究表明其与微管动力学有关。有丝分裂驱动蛋白是一类分子马达，也与微管相互作用，是正常有丝分裂功能所必需的。SB-715992是一种新型药物，可抑制一种名为驱动蛋白纺锤体蛋白的有丝分裂驱动蛋白的功能并导致细胞死亡。
20例先前接受过治疗的晚期RCC患者参加了这项SB-715992的II期试验，以缓解率作为主要终点。
没有患者达到完全缓解或部分缓解。6例患者病情稳定，1例患者在12个周期后继续接受治疗。常见毒性包括贫血（80%）、肌酐升高（70%）、淋巴细胞减少（45%）、疲劳（50%）、高血糖（50%）和呼吸困难（45%）。报告的3/4级毒性包括呼吸困难、疲劳、伴有皮肤感染的中性粒细胞减少、头晕、高尿酸血症和高血压。
SB-715992的这一剂量和给药方案对先前接受过治疗的晚期RCC患者似乎没有显著的细胞毒性作用。
