E3803 研究：每周应用伊沙匹隆治疗转移性去势抵抗性前列腺癌男性患者的 II 期临床试验：东部肿瘤协作组研究。
Phase II trial of weekly ixabepilone in men with metastatic castrate-resistant prostate cancer (E3803): a trial of the Eastern Cooperative Oncology Group.
机构信息
University of Wisconsin Carbone Cancer Center, Madison, WI 53705, USA.
出版信息
Clin Genitourin Cancer. 2012 Jun;10(2):99-105. doi: 10.1016/j.clgc.2012.01.009. Epub 2012 Mar 3.
UNLABELLED
Ixabepilone is an epothilone B analogue with activity in a variety of solid malignancies, including prostate cancer. The main dose-limiting toxicity of ixabepilone is myelosuppression when administered by using an every 3-week schedule. Here we evaluate the activity of a weekly ixabepilone in men with metastatic castrate-resistant prostate cancer to minimize hematologic toxicity.
PURPOSE
BMS-247550 (ixabepilone) is an epothilone B analogue with activity in taxane-resistant cancer cell lines. Here we report the activity and toxicity of ixabepilone, administered by using a weekly schedule, in men with metastatic castrate-resistant prostate cancer (CRPC).
EXPERIMENTAL DESIGN
Patients with metastatic CRPC received ixabepilone at 20 mg/m(2) intravenous weekly x 3, in 4-week cycles. This noncomparative study stratified patients to either a chemotherapy naive (CN), prior taxane (Tax) only, or 2 prior cytotoxic (TCx) chemotherapy arm. The primary endpoint was prostate-specific antigen response by using PCWG (Prostate Cancer Working Group) 1 criteria. Secondary endpoints included radiographic response when using RECIST (Response Evaluation Criteria In Solid Tumors).
RESULTS
In total, 124 patients were enrolled, of whom, 109 were eligible (35 CN, 42 Tax, and 32 TCx) for the primary response determination in this study. Prostate-specific antigen responses were seen in 12 (34.3%) of 35, 12 (28.6%) of 42, and 7 (21.9%) of 32 patients with the partial objective response in 5 (22.7%) of 22, 2 (8.0%) of 25, and 0 (0.0%) of 24 patients for the CN, Tax, and TCx arms, respectively. Significant (grade 3/4) neutropenia was seen in 6 (15.4%), 7 (14.6%), and 9 (25.0%); and grade 3/4 sensory neuropathy was seen in 8 (20.5%), 12 (25.0%), and 12 (33.3%) for CN, Tax, and TCx, respectively. Grade 3/4 thrombocytopenia was infrequent and seen in only one patient on the CN and the TCx arm.
CONCLUSION
Ixabepilone was found to have an acceptable toxicity profile when administered by using a weekly schedule with less myelosuppression compared with prior studies when using the every 3-week schedule. Single-agent activity was observed and met prespecified activity levels for the Tax treated arm.
目的
BMS-247550（伊沙匹隆）是一种表鬼臼毒素 B 类似物，对紫杉烷耐药癌细胞系有活性。在此，我们报告每周方案应用伊沙匹隆治疗转移性去势抵抗性前列腺癌（CRPC）患者的疗效和毒性。
实验设计
转移性 CRPC 患者接受每周静脉注射 20mg/m2 的伊沙匹隆，每 3 周 1 次，每 4 周为 1 个周期。本非对照研究将患者分为化疗初治（CN）、仅接受紫杉烷治疗（Tax）或 2 线细胞毒性化疗（TCx）3 个亚组。主要终点是根据前列腺癌工作组（PCWG）1 标准评估前列腺特异抗原（PSA）应答。次要终点包括使用实体瘤反应评价标准（RECIST）评估的放射学应答。
结果
共纳入 124 例患者，其中 109 例符合本研究的主要应答评估标准（35 例 CN、42 例 Tax、32 例 TCx）。PSA 应答见于 35 例中的 12 例（34.3%）、42 例中的 12 例（28.6%）和 32 例中的 7 例（21.9%），其中部分客观缓解分别见于 22 例中的 5 例（22.7%）、25 例中的 2 例（8.0%）和 24 例中的 0 例。CN、Tax 和 TCx 亚组中，显著（3/4 级）中性粒细胞减少的发生率分别为 6 例（15.4%）、7 例（14.6%）和 9 例（25.0%）；3/4 级感觉神经病的发生率分别为 8 例（20.5%）、12 例（25.0%）和 12 例（33.3%）。CN 和 TCx 亚组中各有 1 例血小板减少症为 3/4 级。
结论
与每 3 周方案相比，每周方案应用伊沙匹隆时骨髓抑制发生率更低，毒性谱可接受。与 Tax 治疗组的预先设定的活性水平相比，观察到单药活性。
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