Machiels Jean-Pascal, Mazzeo Filomena, Clausse Marylene, Filleul Bertrand, Marcelis Luc, Honhon Brigitte, D'Hondt Lionel, Dopchie Catherine, Verschaeve Vincent, Duck Lionel, Verhoeven Didier, Jousten Peter, Bonny Marie-Alix, Moxhon Anne-Marie, Tombal Bertrand, Kerger Joseph
Department of Medical Oncology and Urology, Université Catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
J Clin Oncol. 2008 Nov 10;26(32):5261-8. doi: 10.1200/JCO.2008.16.9524. Epub 2008 Sep 15.
To assess the efficacy and toxicity of the addition of estramustine to docetaxel (D) for the treatment of metastatic hormone-refractory prostate cancer.
One hundred fifty patients were randomly assigned to D alone (35 mg/m(2) on days 2 and 9, every 3 weeks) or D in combination with estramustine (D/E; 280 mg orally three times a day on days 1 to 5 and 8 to 12, every 3 weeks). All patients received prednisone (10 mg/d). The primary end point was prostate-specific antigen (PSA) response rate, which was defined as a decrease in PSA > or = 50% from baseline. The study was powered to test the hypothesis that D/E would improve the PSA response rate by 25%.
The PSA response rate was not statistically different between the two groups. PSA of less than 4 ng/mL occurred in 29 (41%) of 71 patients receiving D/E and in 17 (25%) of 69 patients receiving D (P = .05). No significant differences were found for median time to PSA progression (D/E, 6.9 months; D, 7.3 months) or median overall survival time (D/E, 19.3 months; D, 21 months). More patients had at least one grade 3 or 4 toxicity with D/E (45%) compared with D (21%; P = .005), mainly as a result of grade 3 or 4 GI toxicity (P = .05). Serious adverse events were more frequent with D/E (n = 20) than with D (n = 9; P = .04).
The addition of estramustine to weekly D does not provide any clinically relevant advantage. Both regimens are well tolerated, although the toxicity profile favors D without estramustine.
评估在多西他赛（D）基础上加用雌莫司汀治疗转移性激素难治性前列腺癌的疗效和毒性。
150例患者被随机分为单纯多西他赛组（每3周，第2天和第9天给予35mg/m²）或多西他赛联合雌莫司汀组（D/E；每3周，第1至5天及8至12天每天口服280mg，分3次服用）。所有患者均接受泼尼松（10mg/d）治疗。主要终点为前列腺特异性抗原（PSA）反应率，定义为PSA较基线水平降低≥50%。该研究旨在检验D/E可使PSA反应率提高25%这一假设。
两组间PSA反应率无统计学差异。接受D/E治疗的71例患者中有29例（41%）PSA降至4ng/mL以下，接受D治疗的69例患者中有17例（25%）PSA降至4ng/mL以下（P = 0.05）。PSA进展的中位时间（D/E为6.9个月；D为7.3个月）或总生存时间的中位数（D/E为19.3个月；D为21个月）均无显著差异。与D组（21%；P = 0.005）相比，D/E组更多患者至少出现1次3级或4级毒性反应，主要是由于3级或4级胃肠道毒性（P = 0.05）。D/E组严重不良事件（n = 20）比D组（n = 9；P = 0.04）更常见。
每周使用多西他赛时加用雌莫司汀未显示出任何临床相关优势。两种方案耐受性均良好，尽管毒性特征显示不加用雌莫司汀的多西他赛方案更具优势。
