Posadas Edwin M, Undevia Samir, Manchen Elizabeth, Wade James L, Colevas A Dimitrios, Karrison Theodore, Vokes Everett E, Stadler Walter M
University of Chicago Phase II Consortium, Section of Hematology/Oncology, Chicago, Illinois 60637, USA.
Cancer Biol Ther. 2007 Apr;6(4):490-3. doi: 10.4161/cbt.6.4.3831.
Ixabepilone (BMS-247550) is a semi-synthetic analog of epothilone B that has been characterized as a microtubule stabilizing agent with a mechanism of action distinct from taxanes. Suggestion of activity in renal cell carcinoma (RCC) has been seen in early clinical studies.
Eligible patients had metastatic RCC as well as ECOG performance status 0-2 and normal organ function. Patients received ixabepilone at a dose of 40 mg/m2 intravenously over three hours every 21 days. There was no restriction on RCC histology or prior treatment type, but prior treatment with tubule inhibitors was not allowed. The primary endpoint was RECIST defined response and radiographic evaluations were performed every three cycles. Toxicity evaluations utilized CTCAE v3.0 and were performed every cycle. Using a Simon two-stage optimal design with alpha = 0.1, beta = 0.1, a null hypothesized response rate of 0.05 and an alternative response rate of 0.2, an initial 12 patients were to be accrued with full accrual of 37 patients if at least one response were observed.
A median of five cycles were administered. No objective responses were observed in the first 12 evaluable patients, and six patients showed stable disease for more than 18 weeks on therapy. Median time to progression among those with objective progression was nine weeks. One patient experienced grade 4 anemia and lymphopenia. Grade 3 adverse events included lymphopenia, neutropenia, leukopenia, diarrhea, and infection. Common grade 2 toxicities included alopecia, fatigue and anemia.
Ixabepilone administered at a dose of 40 mg/m2 every 21 days should not be advanced for further study in metastatic RCC. Given previous results, however, other dosing schedules may be worthy of further investigation.
伊沙匹隆（BMS - 247550）是埃坡霉素B的半合成类似物，已被确定为一种微管稳定剂，其作用机制与紫杉烷类不同。早期临床研究显示其对肾细胞癌（RCC）有活性迹象。
符合条件的患者患有转移性肾细胞癌，东部肿瘤协作组（ECOG）体能状态为0 - 2，且器官功能正常。患者接受伊沙匹隆治疗，剂量为40mg/m²，静脉滴注3小时，每21天一次。对肾细胞癌的组织学类型或既往治疗类型没有限制，但不允许既往使用过肾小管抑制剂治疗。主要终点是根据实体瘤疗效评价标准（RECIST）定义的反应，每三个周期进行一次影像学评估。毒性评估采用美国国立癌症研究所常见不良反应事件评价标准（CTCAE）v3.0，每周期进行一次。采用Simon两阶段最优设计，α = 0.1，β = 0.1，无效假设反应率为0.05，备择反应率为0.2，最初纳入12例患者，如果观察到至少一例反应，则完全纳入37例患者。
中位给药周期数为5个。在前12例可评估患者中未观察到客观反应，6例患者在治疗期间疾病稳定超过18周。出现客观进展的患者的中位进展时间为9周。1例患者出现4级贫血和淋巴细胞减少。3级不良事件包括淋巴细胞减少、中性粒细胞减少、白细胞减少、腹泻和感染。常见的2级毒性包括脱发、疲劳和贫血。
每21天给予40mg/m²剂量的伊沙匹隆不应推进用于转移性肾细胞癌的进一步研究。然而，鉴于先前的结果，其他给药方案可能值得进一步研究。
