Division of Oncology, University of Washington, Seattle, Washington 98109, USA.
Urology. 2011 May;77(5):1166-71. doi: 10.1016/j.urology.2011.01.006.
To determine the activity and tolerability of 100-mg once-daily (QD) dasatinib in patients with metastatic castration-resistance prostate cancer (CRPC). Dasatinib, an oral Src family kinase inhibitor, has demonstrated both preclinical and clinical activity with twice-daily dosing in patients with metastatic CRPC.
Chemotherapy-naive men with metastatic CRPC and increasing prostate-specific antigen levels were treated with dasatinib 100 mg QD. The primary measurement was a composite lack of disease progression, according to the Prostate Cancer Working Group 2 criteria, determined every 12 weeks during the study. The other analyses included changes in the prostate-specific antigen level, bone lesions, soft tissue disease, and bone turnover markers (urine N-telopeptide and bone alkaline phosphatase).
The present trial was designed before the publication of the recent Prostate Cancer Working Group 2 criteria; however, the analyses are presented to conform to the updated guidelines. A total of 48 patients received dasatinib. A lack of disease progression was observed in 21 patients (44%) at week 12 and in 8 (17%) at week 24. Urine N-telopeptide was reduced by ≥40% from baseline in 22 (51%) of 43 patients, and bone alkaline phosphatase was decreased in 26 (59%) of 44 patients. Dasatinib was well-tolerated, with only 6 patients (13%) with drug-related grade 3-4 adverse events and 3 (6%) with grade 3 adverse events. The most common treatment-related adverse events (≥20%) were fatigue, nausea, diarrhea, headache, and anorexia.
Dasatinib 100 mg QD has a favorable safety profile and maintains a similar degree of activity as the previously reported twice-daily dosing schedules. These data support additional study of dasatinib 100 mg QD for metastatic CRPC.
确定每日一次（QD）100mg 达沙替尼在转移性去势抵抗性前列腺癌（CRPC）患者中的活性和耐受性。达沙替尼是一种口服Src 家族激酶抑制剂，在接受过化疗的转移性 CRPC 患者中，每日两次给药显示出了临床前和临床活性。
化疗初治的转移性 CRPC 且前列腺特异性抗原（PSA）水平升高的男性患者接受达沙替尼 100mg QD 治疗。主要测量指标是根据前列腺癌工作组 2 标准确定的无疾病进展的复合指标，在研究期间每 12 周进行一次评估。其他分析包括 PSA 水平、骨病变、软组织疾病和骨转换标志物（尿 N-端肽和骨碱性磷酸酶）的变化。
本试验是在最近的前列腺癌工作组 2 标准公布之前设计的；然而，为了符合更新的指南，对分析结果进行了呈现。共有 48 名患者接受了达沙替尼治疗。在第 12 周和第 24 周，分别有 21 名（44%）和 8 名（17%）患者观察到无疾病进展。在 43 名可评估患者中，有 22 名（51%）患者的尿 N-端肽较基线降低≥40%，44 名可评估患者中有 26 名（59%）患者的骨碱性磷酸酶降低。达沙替尼耐受性良好，仅有 6 名（13%）患者出现与药物相关的 3-4 级不良事件，3 名（6%）患者出现 3 级不良事件。最常见的与治疗相关的不良事件（≥20%）是疲劳、恶心、腹泻、头痛和厌食。
达沙替尼 100mg QD 的安全性良好，其活性与之前报告的每日两次给药方案相似。这些数据支持进一步研究达沙替尼 100mg QD 治疗转移性 CRPC。
