Ixabepilone (epothilone B analogue BMS-247550) is active in chemotherapy-naive patients with hormone-refractory prostate cancer: A southwest oncology group trial S0111
Ixabepilone (epothilone B analogue BMS-247550) is active in chemotherapy-naive patients with hormone-refractory prostate cancer: A southwest oncology group trial S0111
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DOI：
10.1200/jco.2005.02.4448
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发表时间：
2005-12-01
影响因子：
45.3
通讯作者：
Crawford, ED
中科院分区：
文献类型：
--
作者：
Hussain, M;Tangen, CM;Crawford, ED
目的埃泊霉素是一类新的微管蛋白聚合剂，在紫杉烷敏感和耐药的肿瘤模型中具有活性。我们评估了ixabepilone （BMS-247550）在转移性激素难治性前列腺癌（HBPC）患者中的疗效。方法符合条件的患者为化疗初期转移性HRPC， Zubrod性能状态为0 ~ 2，器官功能正常。所有患者每3周接受BMS-247550治疗，剂量为40 mg/m(2)，持续3小时。主要终点是达到前列腺特异性抗原（PSA）应答的患者比例。结果本组共48例转移性HRPC患者。42例患者符合条件，中位年龄为73岁，中位PSA水平为111 ng/mL；78%有骨转移或骨和软组织转移，88%在登记时有客观的放射学疾病进展。3级和4级不良事件（ae）分别发生在16例和3例患者中。所有4级毒性均为中性粒细胞减少或白细胞减少。最常见的3级ae是神经病变（8例）、血液毒性（7例）、流感样症状和感染（各5例）。无3/4级血小板减少症或5级ae。有14例确诊的PSA反应（33%;95% CI， 20%至50%）；72%的PSA应答者的PSA下降幅度大于80%，两名患者达到了无法检测到的PSA。估计中位无进展生存期为6个月（95% CI， 4至8个月），中位生存期为18个月（95% CI， 13至24个月）。结论ixabepilone在化疗初期转移性HRPC患者中显示出活性。主要毒性为中性粒细胞减少和神经病变。需要进一步测试以确定其相对于标准疗法的活性。
PurposeThe epothilones are a new class of tubulin-polymerizing agents with activity in taxane-sensitive and resistant tumor models. We evaluated ixabepilone (BMS-247550) in patients with metastatic hormone-refractory prostate cancer (HBPC).MethodsEligible patients had chemotherapy-naive metastatic HRPC, a Zubrod performance status of 0 to 2, and adequate organ function. All patients received BMS-247550 at 40 mg/m(2) over 3 hours every 3 weeks. The primary end point was proportion of patients achieving a prostate-specific antigen (PSA) response.ResultsForty-eight patients with metastatic HRPC were registered. Forty-two patients were eligible, with a median age of 73 years and a median PSA level of 111 ng/mL; 78% had bone-only or bone and soft tissue metastases, and 88% had objective radiologic disease progression at registration. Grade 3 and 4 adverse events (AEs) occurred in 16 and three patients, respectively. All grade 4 toxicities were neutropenia or leukopenia. The most frequent grade 3 AEs were neuropathy (eight patients), hematologic toxicity (seven patients), flu-like symptoms, and infection (five patients each). There were no grade 3/4 thrombocytopenia or grade 5 AEs. There were 14 confirmed PSA responses (33%; 95% CI, 20% to 50%); 72% of PSA responders had declines greater than 80%, and two patients achieved an undetectable PSA. The estimated median progression-free survival is 6 months (95% CI, 4 to 8 months), and the median survival is 18 months (95% CI, 13 to 24 months).ConclusionIxabepilone has demonstrated activity in patients with chemotherapy-naive metastatic HRPC. Major toxicities were neutropenia and neuropathy. Further testing to define its activity relative to standard therapy is warranted.