Iversen P, Rasmussen F, Asmussen C, Christensen I J, Eickhoff J, Klarskov P, Larsen E, Mogensen P, Mommsen S, Rosenkilde P
Danish Prostatic Cancer Group (DAPROCA), Hvidovre Hospital, Copenhagen, Denmark.
J Urol. 1997 Mar;157(3):929-34.
We compared the effect of 560 mg. estramustine phosphate daily to placebo as a supplement to standard palliative therapy in patients with progressive disease after bilateral orchiectomy as first line therapy for metastatic prostate cancer.
In a double-blind multicenter study 131 patients with progressing metastatic hormone refractory prostate cancer were randomized to receive 280 mg. estramustine phosphate 2 times daily versus placebo. End points were clinical progression and death. Adverse events, decrease in prostate specific antigen (PSA) and subjective response were also assessed.
Adverse events were common in both groups but breast tenderness/gynecomastia and diarrhea were more frequent among patients in the estramustine phosphate group. Subjective responses were few (9 of 50 estramustine phosphate and 4 of 57 placebo cases, p = 0.15). Median observation time for survival was 43 months and 124 patients died. Median time to subjective progression and median overall survival did not differ significantly between the 2 groups at 4.6 and 9.4 months in the estramustine phosphate group versus 5.0 and 6.1 months in the placebo group. Of 61 patients in the estramustine phosphate group 29 achieved a reduction in PSA of more than 25% at 1 month of followup compared to only 3 of 68 receiving placebo. A decrease in PSA after 1 month correlated significantly with survival.
Although this study did not prove estramustine phosphate to be superior to placebo in terms of protocol end points, it generates the hypothesis that prolonged survival may be achieved with estramustine phosphate treatment in a subgroup of patients and that this may be predicted by a decrease in PSA after 1 month of therapy.
我们比较了每日560毫克磷酸雌莫司汀与安慰剂作为标准姑息治疗补充药物，对双侧睾丸切除术后疾病进展的转移性前列腺癌患者的疗效，双侧睾丸切除术是转移性前列腺癌的一线治疗方法。
在一项双盲多中心研究中，131例转移性激素难治性前列腺癌进展患者被随机分为两组，分别接受每日2次、每次280毫克磷酸雌莫司汀治疗或安慰剂治疗。终点指标为临床进展和死亡。还评估了不良事件、前列腺特异性抗原（PSA）降低情况和主观反应。
两组不良事件均常见，但磷酸雌莫司汀组患者乳房压痛/男性乳房发育和腹泻更为频繁。主观反应较少（磷酸雌莫司汀组50例中有9例，安慰剂组57例中有4例，p = 0.15）。生存的中位观察时间为43个月，124例患者死亡。磷酸雌莫司汀组的主观进展中位时间和总生存中位时间与安慰剂组相比无显著差异，分别为4.6个月和9.4个月，安慰剂组为5.0个月和6.1个月。在磷酸雌莫司汀组的61例患者中，29例在随访1个月时PSA降低超过25%，而接受安慰剂的68例中只有3例。1个月后PSA降低与生存显著相关。
尽管本研究未证明磷酸雌莫司汀在方案终点方面优于安慰剂，但它提出了一个假设，即磷酸雌莫司汀治疗可能使一部分患者延长生存期，且这可能通过治疗1个月后PSA降低来预测。
