Walz P H, Björk P, Gunnarsson P O, Edman K, Hartley-Asp B
Department of Urology, Kreiskrankenhaus Lüdenscheid, Germany.
Clin Cancer Res. 1998 Sep;4(9):2079-84.
Estracyt (EMP) has been used for the treatment of hormone refractory prostate cancer for many years. Recently, new data from combination studies have given rise to new interest in this old drug. Explanations for the synergy found in the clinic are many, but one major factor may be the previous indication that the drug accumulates in the prostate tumor. We have, therefore, examined the level of the four metabolites, estromustine (EoM), estramustine (EaM), estrone, and estradiol in the tumor and serum of 14 patients with T2 and T3 prostate cancer receiving a single i.v. dose of 600 mg of EMP, about 12 h before radical prostatectomy. Because it has been suggested that the uptake into the prostate tumor is due to binding to the estramustine binding protein (EMBP), we have in addition measured the level of EMBP in the prostate tumor tissue. The main serum and tissue metabolite in all patients was EoM followed by EaM, estrone, and estradiol. The levels for EoM ranged from 63.8-162.8 ng/ml in the serum and from 64.8-1209 ng/ml in the prostate tumor, resulting in a mean ratio for serum to tumor of 1:5. The levels for EaM ranged from 8.3-51.4 ng/ml in the serum and 73.9-563.4 ng/ml in the tumor, giving a mean ratio for serum to tumor of 1:13. The levels of EMBP were higher in T3 tumors than in T2 tumors, 54.1 and 40.7 ng/g tissue, respectively. A significant correlation was found between the levels of EaM (r = 0.60) and the levels of EMBP in the tumor. These data demonstrate that 12 h after a single i.v. dose of 600 mg of EMP the levels of the cytotoxic metabolites EoM and EaM are substantially higher in the tumor than in the serum of the same patient and that a correlation exists between the levels of EaM in the tumor and the levels of EMBP. Thus, this supports the hypothesis that the EMBP is responsible for the retention of EoM and EaM in the prostate tumor.
癌腺治（EMP）已用于治疗激素难治性前列腺癌多年。最近，联合研究的新数据引发了人们对这种老药的新兴趣。临床上发现协同作用的解释有很多，但一个主要因素可能是先前有迹象表明该药物会在前列腺肿瘤中蓄积。因此，我们检测了14例T2和T3期前列腺癌患者在前列腺根治术前约12小时静脉注射单次剂量600mg EMP后，肿瘤和血清中四种代谢物——雌莫司汀（EoM）、雌二醇氮芥（EaM）、雌酮和雌二醇的水平。由于有人提出前列腺肿瘤对药物的摄取是由于与雌二醇氮芥结合蛋白（EMBP）结合，我们还检测了前列腺肿瘤组织中EMBP的水平。所有患者血清和组织中的主要代谢物都是EoM，其次是EaM、雌酮和雌二醇。EoM的血清水平范围为63.8 - 162.8 ng/ml，前列腺肿瘤中的水平为64.8 - 1209 ng/ml，血清与肿瘤的平均比值为1:5。EaM的血清水平范围为8.3 - 51.4 ng/ml，肿瘤中的水平为73.9 - 563.4 ng/ml，血清与肿瘤的平均比值为1:13。T3期肿瘤中EMBP的水平高于T2期肿瘤，分别为54.1和40.7 ng/g组织。肿瘤中EaM的水平与EMBP的水平之间存在显著相关性（r = 0.60）。这些数据表明，静脉注射单次剂量600mg EMP 12小时后，细胞毒性代谢物EoM和EaM在肿瘤中的水平显著高于同一患者的血清水平，且肿瘤中EaM的水平与EMBP的水平之间存在相关性。因此，这支持了EMBP负责EoM和EaM在前列腺肿瘤中潴留的假说。
