Kattan Joseph G, Farhat Fady S, Chahine Georges Y, Nasr Fady L, Moukadem Walid T, Younes Fariha C, Yazbeck Nadine J, Ghosn Marwan G
Hôtel-Dieu de France University Hospital, Beirut, Lebanon.
Invest New Drugs. 2008 Feb;26(1):75-9. doi: 10.1007/s10637-007-9074-3. Epub 2007 Sep 6.
Treatment options for patients with hormone refractory prostate cancer (HRPC) showed unsatisfactory outcomes. Docetaxel-based combinations could offer more promising and tolerated results. A phase II trial was conducted with the combination of zoledronic acid, docetaxel and estramustine. Eligibility consisted of metastatic prostate adenocarcinoma with objective progression or rising prostate specific antigen levels (PSA) despite androgen deprivation therapy. Zoledronic acid was given at a dose of 4 mg on day 1, docetaxel (25 mg/m2) on days 1, 8 and 15, and estramustine orally at 140 mg two times daily on days 1 to 21 of a 28-day cycle. Twenty-seven patients were enrolled between October 2002 and November 2004. Median age was 68 years (53-83 years). A total of 124 cycles were administered with a median of 4.6 cycles per patient (1-8 cycles). The major toxicities were grades 1 to 3 anemia (55%), fatigue (15%), alopecia (11%) and hypocalcemia (11%). Two patients presented with deep venous thrombosis and died from pulmonary embolism. Another third patient died from Stevens-Johnson syndrome and grade 4 hepatic toxicity. Out of the 25 patients assessed for efficacy, 13 (52%) had a biologic response (>50% PSA decline). Three (21%) patients among the 14 with measurable disease had objective response: 1 complete response (CR) and 2 partial responses (PR). Response duration was 2 months for PR and 4 months for CR. A total of 12 patients (48%) experienced clinical benefit with pain reduction. This combination seemed effective; however toxic deaths especially from venous thrombosis counterbalanced the advantage of this regimen.
激素难治性前列腺癌（HRPC）患者的治疗方案效果并不理想。基于多西他赛的联合疗法可能会带来更有前景且耐受性更好的结果。开展了一项关于唑来膦酸、多西他赛和雌莫司汀联合使用的II期试验。入选标准为转移性前列腺腺癌，尽管接受了雄激素剥夺治疗，但仍有客观进展或前列腺特异性抗原水平（PSA）升高。在28天周期的第1天给予唑来膦酸4毫克，在第1、8和15天给予多西他赛（25毫克/平方米），在第1至21天每天口服两次雌莫司汀，每次140毫克。2002年10月至2004年11月期间共招募了27名患者。中位年龄为68岁（53 - 83岁）。总共进行了124个周期的治疗，每位患者的中位周期数为4.6个（1 - 8个周期）。主要毒性反应为1至3级贫血（55%）、疲劳（15%）、脱发（11%）和低钙血症（11%）。两名患者出现深静脉血栓并死于肺栓塞。另一名患者死于史蒂文斯 - 约翰逊综合征和4级肝毒性。在评估疗效的25名患者中，13名（52%）有生物学反应（PSA下降>50%）。在14名可测量疾病的患者中，3名（21%）有客观反应：1名完全缓解（CR）和2名部分缓解（PR）。PR的缓解持续时间为2个月，CR为4个月。共有12名患者（48%）在疼痛减轻方面有临床获益。这种联合疗法似乎有效；然而，尤其是静脉血栓导致的毒性死亡抵消了该方案的优势。
