Randomized phase II study comparing paclitaxel and carboplatin versus mitoxantrone in patients with hormone-refractory prostate cancer
Randomized phase II study comparing paclitaxel and carboplatin versus mitoxantrone in patients with hormone-refractory prostate cancer
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DOI：
10.1016/j.urology.2005.08.046
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发表时间：
2006-02-01
期刊：
影响因子：
2.1
通讯作者：
Bay, JO
中科院分区：
文献类型：
--
作者：
Cabrespine, A;Guy, L;Bay, JO
目标。米托蒽酮/泼尼松是2002年激素耐药前列腺癌(HRPC)的姑息性参考疗法。紫杉醇和卡铂在HRPC中显示出抗肿瘤活性。并与米托蒽醌治疗效果进行比较。进行了一项随机的第二阶段研究，其中包括40名未接受化疗的HRPC患者。试验组A给予紫杉醇175 mg/m(2)，每3周为一周期；卡铂为每3周一周期，曲线下面积为5。B组患者接受米托蒽醌治疗(12 mg/m(2)，每3周为一周期)。所有患者均接受小剂量强的松治疗。主要终点是前列腺特异性抗原反应。前列腺特异性抗原对紫杉醇和卡铂的应答显著高于米托蒽醌(40%[95%可信区间18.5%~61.5%]和10%[95%可信区间1%~32%]，P=0.031)，且更持久(8.6vs 2个月，P=0.015)。在接受紫杉醇和卡铂治疗的可测量疾病患者中，有一种趋势是有比接受米托蒽醌治疗的患者有更高的客观应答率的趋势(23%[95%可信区间5.3%至55%]与没有客观应答者，P=0.060)。紫杉醇和卡铂组的中位总生存期为14.5个月，而米托蒽醌组的中位生存期为11.1个月。接受紫杉醇和卡铂治疗的患者敏感性神经病变的发生率显著高于对照组(50%比0%，P=0.00026)。紫杉醇和卡铂的3周方案与米托蒽醌治疗HRPC相比，诱导了更大和更持久的前列腺特异性抗原反应。紫杉醇所致的主要加性毒性为周围神经病变。紫杉醇和卡铂方案的研究值得进行大规模的III期研究。
Objectives. Mitoxantrone/prednisone was the 2002 palliative reference treatment for hormone-refractory prostate cancer (HRPC). Paclitaxel and carboplatin has demonstrated antitumor activity in HRPC. The therapeutic benefit of such treatment was compared with that of mitoxantrone.Methods. A randomized Phase II study was conducted that included 40 patients with HRPC who had not undergone chemotherapy. Patients in arm A received paclitaxel (175 mg/m(2) every 3-week cycle) and carboplatin (area under the curve of 5 every 3-week cycle). Patients in arm B received mitoxantrone (12 mg/m(2) every 3-week cycle). All the patients treated were receiving low-dose prednisone. The primary endpoint was the prostate-specific antigen response.Results. The prostate-specific antigen response to paclitaxel and carboplatin was significantly greater (40% [95% confidence interval 18.5% to 61.5%] versus 10% [95% confidence interval 1% to 32%], P = 0.031) and more durable (8.6 versus 2 months, P = 0.015) than the response to mitoxantrone. A tendency was noted for patients with measurable disease who were receiving paclitaxel and carboplatin to have a somewhat greater objective response rate than those who received mitoxantrone (23% [95% confidence interval 5.3% to 55%] versus no objective response, P = 0.060). The median overall survival was 14.5 months for the paclitaxel and carboplatin arm compared with 11.1 months for the mitoxantrone arm. The group given paclitaxel and carboplatin had significantly greater rates of sensitive neuropathy (50% versus 0%, P = 0.00026).Conclusions. The 3-week regimen of paclitaxel and carboplatin induced a greater and more durable prostate-specific antigen response than did mitoxantrone for HRPC treatment. The major additive toxicity induced was peripheral neuropathy due to paclitaxel. Investigations with paclitaxel and carboplatin regimens merit large Phase III studies.