多西他赛加泼尼松3周方案失败后联合雌二醇氮芥治疗激素难治性前列腺癌

Combination with estramustine in treatment of hormone-refractory prostate cancer after treatment failure of docetaxel and prednisone three-week regimen

目的激素难治性前列腺癌（ hormone refractory prostate cancer, HRPC）的治疗，在2004年取得了突破性进展，TAX327研究证实多西他赛联合泼尼松3wk方案可以延长病人的生存期，从而确立了其一线标准化疗方案的地位。但是，多西他赛联合泼尼松方案失败后的治疗选择仍然是一难题，为此，我们观察多西他赛联合雌二醇氮芥及泼尼松三联方案在一线标准方案失败后治疗HRPC的疗效和安全性。方法2005年11月至2007年3月，6例HRPC在多西他赛联合泼尼松3wk方案治疗过程中病情恶化（血PSA升高）时，用多西他赛联合雌二醇氮芥及泼尼松治疗。治疗方案：多西他赛75mg／m^2，d1，强的松5mg bid，d1起连续应用，雌二醇氮芥280mg，2次，d，d1起连用5d。21d为1疗程。病人平均年龄75．8a，血睾酮维持去势水平，WHO体力状态评分≤2，骨髓、心、肝、肾等重要脏器功能正常。估计生存时间〉3mo。疗效及不良反应判断标准：①血PSA下降〉50％，且维持〉3wk判断为有效。②可测量病灶按RECIST实体瘤评价标准评价。③骨痛者按主诉疼痛程度分级法（VRS）评价，评分下降1级为有效。④不良反应按WHO不良反应标准评定。结果6例共完成27个疗程。PSA有效5例，有效率为83.3％。有效病人PSA从治疗前的10．9～606．2（223．6±218．0）mg／mL下降到治疗后最低1．1～127．6（61．5±50．4）ng／mL。1例肺转移者，转移灶为稳定。1例骨痛者VRS疼痛评分从Ⅱ下降到Ⅰ。到分析日止，已死亡1例。此例从诊断激素非依赖前列腺癌到死亡共53mo。5例存活者从诊断激素非依赖前列腺癌起已存活14～36mo。主要不良反应为骨髓抑制（100％），脱发（100％），乏力（67％）等。结论多西他赛联合雌二醇氮芥及泼尼松三联方案对多西他赛联合泼尼松3wk方案治疗失败后的病人疗效肯定，毒副反应可以耐受，值得进一步观察研究。

Objective TAX 327 study demonstrated docetaxel plus prednisone given every three weeks could significantly prolong survival among men with hormone refractory prostate cancer （HRPC）. But after failure of this schedule, the treatment option is very difficulty. We evaluate the efficacy and safety of docetaxel plus estramustine and prenisone for the treatment of HRPC after treatment failure of docetaxel plus prednisone given every three weeks. Methods Between November 2005 and March 2007, 6 patients （mean age, 75.8 years; age range, 62-82 years） with HRPC were treated with prednisone （5 mg twice daily）, docetaxel （75mg/m^2, given every 3 weeks） and estramustine （280 mg twice daily on days one through 5, given every 3 weeks） after treatment failure of the schedule of docetaxel plus prednisone given every three weeks. Results Of 6 eliaible oatients. PSA levels decreased by at least 50% in 5 cases （83.3%）： It decreased from 10.9-606.2 （223.6±218.0）ng/mL to 1.1-127.6（61.5±50.4） ng/mL after the treatment. Among 5 effective patients, stable disease of lung metastases was obtained in 1 case and bone pain relief in 1 case. Grade 3 or 4 myelosuppression occurred in 66.7% of the patients. The survival time for the 1 died patient was 53 months from diagnosis of androgen independent prostate cancer. 5 cases still were alive, the range of survival time were 14-36 months after diagnosis of androgen independent prostate cancer. Conclusions Docetaxel （given every 3 weeks） plus estramustine and prednisone is an effective and well-tolerated regimen in patients with HRPC after treatment failure of docetaxel plus prednisone given every three weeks.