一项关于多西他赛每周给药与长春瑞滨每周给药作为雄激素非依赖性前列腺癌患者一线化疗方案的前瞻性、开放标签、随机II期试验。

A prospective, open label, randomized phase II trial of weekly docetaxel versus weekly vinorelbine as first line chemotherapy in patients with androgen independent prostate cancer.

作者信息

Krainer Michael, Tomek Sandra, Elandt Katarzyna, Horak Peter, Albrecht Walter, Eisenmenger Michael, Höltl Wolfgang, Schramek Paul, Stackl Walter, Zielinski Christoph, Reibenwein Jochen

机构信息

Department of Internal Medicine I, Division of Oncology and Cancer Center, Medical University of Vienna, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.

出版信息

J Urol. 2007 Jun;177(6):2141-5; discussion 2145. doi: 10.1016/j.juro.2007.01.148.

DOI:10.1016/j.juro.2007.01.148

PMID:17509302

Abstract

PURPOSE

In previous phase I to III studies docetaxel and vinorelbine have shown promising activity in androgen independent prostate cancer. In the present trial we assessed the efficacy and tolerability of single agent low dose docetaxel vs vinorelbine in patients with advanced androgen independent prostate cancer.

MATERIALS AND METHODS

A total of 40 chemotherapy naive patients with histologically proven androgen independent prostate cancer, adequate androgen ablation, and clinical and/or biochemical progression were randomly assigned to receive either 25 mg/m(2) docetaxel (arm A) or 25 mg/m(2) vinorelbine (arm B) weekly. Treatment was continued until clinical and/or biochemical progression. In cases of progression patients switched to the alternative treatment arm. The primary end point was time to disease progression. Secondary end points included prostate specific antigen response rates in sequential treatment, analgesic response and toxicity.

RESULTS

The current analysis showed a doubled risk of progression in treatment arm B. The median time to first disease progression was 14.5 months for arm A vs 4.4 months for arm B. The proportion of patients with a greater than 50% prostate specific antigen decrease on first line therapy was significantly higher in arm A (62.5%) compared to arm B (11.1%) (p = 0.0033). After progression to docetaxel second line vinorelbine yielded a greater than 50% prostate specific antigen response rate of 28.6% vs 62.5% for second line docetaxel. Clinically significant toxicity occurred more often in arm B with neutropenia grade 4 seen in 22% and grade 3 in 28% of patients (p = 0.0005) during the first treatment phase.

CONCLUSIONS

While weekly application of both cytotoxic agents was well tolerated, this study demonstrates the superiority of docetaxel vs vinorelbine as monotherapy in the treatment of androgen independent prostate cancer.

摘要

目的

在之前的I至III期研究中，多西他赛和长春瑞滨在雄激素非依赖性前列腺癌中显示出有前景的活性。在本试验中，我们评估了单药低剂量多西他赛与长春瑞滨在晚期雄激素非依赖性前列腺癌患者中的疗效和耐受性。

材料与方法

总共40例未经化疗、组织学证实为雄激素非依赖性前列腺癌、雄激素充分去除且有临床和/或生化进展的患者被随机分配，每周接受25mg/m²多西他赛（A组）或25mg/m²长春瑞滨（B组）治疗。治疗持续至临床和/或生化进展。进展时患者转至另一治疗组。主要终点是疾病进展时间。次要终点包括序贯治疗中的前列腺特异性抗原反应率、镇痛反应和毒性。

结果

当前分析显示B组进展风险加倍。A组首次疾病进展的中位时间为14.5个月，而B组为4.4个月。一线治疗时前列腺特异性抗原下降超过５０％的患者比例，A组（62.5％）显著高于B组（11.1％）（p = 0.0033）。进展至多西他赛后，二线长春瑞滨的前列腺特异性抗原反应率大于50％为２８.６％，而二线多西他赛为62.5％。在第一个治疗阶段，B组更常发生具有临床意义的毒性，4级中性粒细胞减少见于22％的患者，3级见于28％的患者（p = 0.0005）。