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
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
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DOI：
10.1016/j.juro.2007.01.148
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发表时间：
2007-06-01
影响因子：
6.6
通讯作者：
Reibenwein, Jochen
中科院分区：
文献类型：
--
作者：
Krainer, Michael;Tomek, Sandra;Reibenwein, Jochen
目的：在先前的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希望的活性。在本试验中，我们评估了单药低剂量多西他赛与长春瑞滨治疗晚期雄激素非依赖性前列腺癌患者的疗效和耐受性。共40例未经化疗的组织学证实的雄激素非依赖性前列腺癌患者，充分的雄激素消融，临床和/或生化进展的患者随机接受多西他赛25 mg/m2（A组）或长春瑞滨25 mg/m2（B组）每周一次治疗。治疗持续至临床和/或生化进展。在疾病进展的情况下，患者转换到替代治疗组，主要终点是疾病进展的时间。次要终点包括前列腺特异性抗原反应率在序贯治疗，镇痛反应和toxicity.Results：目前的分析显示，在治疗组B的进展的风险增加了一倍。A组至首次疾病进展的中位时间为14.5个月，B组为4.4个月。一线治疗期间，A组（62.5%）中前列腺特异性抗原下降超过50%的患者比例显著高于B组（11.1%）（p = 0.0033）。进展至多西他赛二线治疗后，长春瑞滨的前列腺特异性抗原应答率大于50%，为28.6%，而多西他赛二线治疗的应答率为62.5%。临床上显着的毒性更经常发生在手臂B与中性粒细胞减少4级22%和3级28%的患者（p = 0.0005）在第一个治疗phase.Conclusions：虽然每周应用两种细胞毒性药物耐受性良好，这项研究表明多西他赛与长春瑞滨作为单药治疗雄激素非依赖性前列腺癌的优越性。
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.