Hussain A, DiPaola R S, Baron A D, Higano C S, Tchekmedyian N S, Johri A R
University of Maryland Greenebaum Cancer Center, Baltimore, MD 21201, USA.
Ann Oncol. 2009 Mar;20(3):492-7. doi: 10.1093/annonc/mdn665. Epub 2008 Dec 15.
Drug resistance mechanisms can reduce response rate and duration in men with castration-resistant prostate cancer (CRPC) receiving docetaxel-based therapy. Patupilone (epothilone B), a microtubule-targeting agent, may be unaffected by some resistance mechanisms. Therefore, a phase II study assessed the patupilone safety and activity in CRPC patients with and without previous chemotherapy.
CRPC patients received patupilone 2.5 mg/m(2) weekly for 3 weeks of a 4-week cycle. Patients were required to have measurable disease or prostate-specific antigen (PSA) progression (levels>20 ng/ml).
All 45 enrolled patients (median age, 69 years) were safety and response assessable. Sixty-four percent had previous chemotherapy (55% had previous taxane therapy). Patients received a median of three patupilone cycles. Patupilone was generally well tolerated. Ten (22%) patients experienced grade 3 diarrhea, six (13%) grade 3 fatigue, and one (2%) grade 3 neuropathy with no neutropenia or thrombocytopenia incidence. Six (13%) patients had >or= 50% decline in PSA (three had previous taxane therapy). No patient with measurable disease had a response. Median overall survival was 13.4 months.
The safety profile of weekly patupilone in CRPC patients compares favorably with that of other microtubule inhibitors. At the dose and schedule tested, patupilone demonstrated minimal activity in CRPC.
耐药机制可降低接受多西他赛治疗的去势抵抗性前列腺癌（CRPC）男性患者的缓解率和缓解持续时间。帕妥珠单抗（埃坡霉素B）是一种微管靶向药物，可能不受某些耐药机制的影响。因此，一项II期研究评估了帕妥珠单抗在既往接受过或未接受过化疗的CRPC患者中的安全性和活性。
CRPC患者接受帕妥珠单抗2.5mg/m²，每周一次，共3周，为期4周的一个周期。患者需有可测量的疾病或前列腺特异性抗原（PSA）进展（水平>20ng/ml）。
所有45例入组患者（中位年龄69岁）均可进行安全性和疗效评估。64%的患者既往接受过化疗（55%既往接受过紫杉烷治疗）。患者接受帕妥珠单抗治疗的中位周期数为3个。帕妥珠单抗总体耐受性良好。10例（22%）患者出现3级腹泻，6例（13%）出现3级疲劳，1例（2%）出现3级神经病变，未发生中性粒细胞减少或血小板减少。6例（13%）患者的PSA下降≥50%（3例既往接受过紫杉烷治疗）。没有可测量疾病的患者出现缓解。中位总生存期为13.4个月。
CRPC患者每周使用帕妥珠单抗的安全性与其他微管抑制剂相比具有优势。在所测试的剂量和给药方案下，帕妥珠单抗在CRPC中显示出最小的活性。
