Weekly high-dose calcitriol and docetaxel in metastatic androgen-independent prostate cancer
Weekly high-dose calcitriol and docetaxel in metastatic androgen-independent prostate cancer
复制标题
DOI：
10.1200/jco.2003.05.117
复制
发表时间：
2003-01-01
影响因子：
45.3
通讯作者：
Henner, WD
中科院分区：
文献类型：
--
作者：
Beer, TM;Eilers, KM;Henner, WD
目的：探讨转移性雄激素非依赖性前列腺癌(AIPC)患者每周口服大剂量骨化三醇(Rocaltrol，Roche PharmPharmticals，巴塞尔，Swifterland)和多西紫杉醇(Taxotere，Avens PharmPharmticals，Bridgewater，NJ)的安全性和有效性。患者保持较少的钙质饮食和较多的口腔水合。前列腺特异性抗原(PSA)应答是主要终点，其定义为4周后PSA水平下降500%。结果：37例患者中有30例(81%，95%可信区间[CI]，68%至94%)达到PSA应答。22名患者(59%；95%氯，43%至75%)证实PSA下降了75%。在15名可测量疾病的患者中，有8名患者(53%；95%CI，27%至799/6)有确认的部分反应。中位进展时间11.4个月(95%CI，8.7~14个月)，中位生存期19.5个月(95%CI，15.3个月不可估量)。1年总生存率为89%(95%CI，74%~95%)。与治疗相关的毒性一般与单药多西紫杉醇的预期相似。在一项探索性的子研究中，骨化三醇或多西紫杉醇的药代动力学不受其伴随药物的存在的影响。结论：每周口服大剂量骨化三醇和多西紫杉醇是一种耐受性良好的治疗AIPC的方案。PSA和可测量的疾病应答率以及进展时间和生存时间与当代单药多西紫杉醇在AIPC中的II期研究相比是有希望的。对这种疗法的进一步研究是有必要的。(C)2003年，由美国临床肿瘤学会提供。
Purpose : To determine the safety and efficacy of weekly high-dose oral calcitriol (Rocaltrol, Roche Pharmaceuticals, Basel, Swifterland) and docetaxel (Taxotere, Aventis Pharmaceuticals, Bridgewater, NJ) in patients with metastatic androgen-independent prostate cancer (AIPC).Patients and Methods: Thirty-seven patients were treated with oral calcitriol (0.5 mug/kg) on day 1 followed by docetaxel (36 mg/m') on day 2, repeated weekly for 6 weeks of an 8-week cycle. Patients maintained a reduced calcium diet and increased oral hydration. Prostate-specific antigen (PSA) response was the primary end point, which was defined as a 500% reduction in PSA level confirmed 4 weeks later.Results: Thirty of 37 patients (81%; 95% confidence interval [CI], 68% to 94%) achieved a PSA response. Twenty-two patients (59%; 95% Cl, 43% to 75%) had a confirmed > 75% reduction in PSA. Eight of the 15 patients with measurable disease (53%; 95% Cl, 27% to 799/6) had a confirmed partial response. Median time to progression was 11.4 months (95% Cl, 8.7 to 14 months), and median survival was 19.5 months (95% Cl, 15.3 months to incalculable). Overall survival at 1 year was 89% (95% Cl, 74% to 95%). Treatment-related toxicity was generally similar to that expected with single-agent docetaxel. Pharmacokinetics of either calcitriol or docetaxel were not affected by the presence of its companion drug in an exploratory substudy.Conclusion: The combination of weekly oral high-dose calcitriol and weekly docetaxel is a well-tolerated regimen for AIPC. PSA and measurable disease response rates as well as time to progression and survival are promising when compared with contemporary phase II studies of single-agent docetaxel in AIPC. Further study of this regimen is warranted. (C) 2003 by American Society of Clinical Oncology.