Division of Oncology, Department of Internal Medicine, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, USA.
J Urol. 2009 Jul;182(1):317-23. doi: 10.1016/j.juro.2009.02.105. Epub 2009 May 17.
Synergy is observed with the combination of capecitabine and docetaxel due to docetaxel mediated up-regulation of thymidine phosphorylase. A phase II trial was performed with the combination for metastatic, castrate resistant prostate cancer.
Eligible patients had metastatic, castrate resistant prostate cancer, no prior chemotherapy for metastatic disease and normal organ function. Docetaxel (36 mg/m(2) per week intravenously) on days 1, 8 and 15, and capecitabine (1,250 mg/m(2) per day in 2 divided doses) on days 5 to 18 were administered in 28-day cycles. The response was assessed every 2 cycles. Biomarker correlative studies were performed on blood dihydropyrimidine dehydrogenase, and the thymidine phosphorylase-to-dihydropyrimidine dehydrogenase and thymidine synthase-to-dihydropyrimidine dehydrogenase ratios in available prostate tumor tissue.
A total of 30 patients with a median age of 69 years were enrolled in the study. We noted bone pain in 21 patients (70%), Gleason score 8 or higher in 18 (60%), measurable disease progression in 9, bone scan progression in 18 and prostate specific antigen progression in 22. Grade 3 or 4 neutropenia was seen in 3 patients and grade 3 hand-foot syndrome was found in 2. No treatment related deaths occurred. A prostate specific antigen response of 50% or greater decrease was observed in 22 patients (73%), of whom 9 (30%) had 90% or greater decrease. A partial response was noted in 5 of 9 patients (56%) with measurable disease. Median time to progression was 6.7 months (90% CI 4.2-7.7) and median overall survival was 22.0 months (90% CI 18.4-25.3).
The combination was well tolerated and it demonstrated favorable response rates with durable remission and survival outcomes.
由于多西紫杉醇介导的胸苷磷酸化酶上调，卡培他滨和多西紫杉醇联合具有协同作用。对转移性去势抵抗性前列腺癌患者进行了联合治疗的 II 期试验。
符合条件的患者患有转移性去势抵抗性前列腺癌，没有转移性疾病的先前化疗，并且器官功能正常。多西紫杉醇（每周 36mg/m²，静脉内）在第 1、8 和 15 天，卡培他滨（每天 1250mg/m²，分为 2 次剂量）在第 5 至 18 天，在 28 天的周期中给药。每 2 个周期评估一次反应。对血液二氢嘧啶脱氢酶以及可用前列腺肿瘤组织中的胸苷磷酸化酶与二氢嘧啶脱氢酶和胸苷合酶与二氢嘧啶脱氢酶的比值进行了生物标志物相关性研究。
共有 30 名中位年龄为 69 岁的患者入组该研究。我们注意到 21 名患者（70%）有骨痛，18 名患者（60%）Gleason 评分 8 或更高，9 名患者（30%）有可测量的疾病进展，18 名患者有骨扫描进展，22 名患者有前列腺特异性抗原进展。3 名患者出现 3 级或 4 级中性粒细胞减少症，2 名患者出现 3 级手足综合征。没有发生与治疗相关的死亡。22 名患者（73%）观察到前列腺特异性抗原反应下降 50%或更多，其中 9 名患者（30%）下降 90%或更多。在 9 名可测量疾病的患者中有 5 名（56%）观察到部分缓解。中位无进展生存期为 6.7 个月（90%CI 4.2-7.7），中位总生存期为 22.0 个月（90%CI 18.4-25.3）。
该联合治疗耐受性良好，具有良好的反应率，并带来持久的缓解和生存结果。
