Tolis G, Ackman D, Stellos A, Mehta A, Labrie F, Fazekas A T, Comaru-Schally A M, Schally A V
Proc Natl Acad Sci U S A. 1982 Mar;79(5):1658-62. doi: 10.1073/pnas.79.5.1658.
Ten patients with prostatic carcinoma--six with stage C and four with stage D disease--were treated for 6 weeks to 12 months with agonistic analogues of luteinizing hormone-releasing hormone (LH-RH). [D-Trp6]LH-RH was given subcutaneously once daily at a dose of 100 microgram and [D-Ser(But)6]des-GlyNH2(10)-LH-RH ethylamide (HOE 766) was given subcutaneously (50 microgram once daily) or intranasally (500 microgram twice daily). In all patients, mean plasma testosterone levels showed a 75% suppression by the third week of treatment and remained low thereafter. This was followed by a decrease or normalization of plasma acid phosphatase levels by the second month of treatment and a 47% decrease in serum alkaline phosphatase by the 10th week of treatment in all but one patient. In patients with stage C disease presenting with prostatism or urinary outflow obstruction, there was a noticeable clinical improvement. In two such patients, a decrease in the size of the prostate was confirmed by ultrasonography. In patients with stage D disease manifested by diffuse bone metastases, there was relief of bone pain, and in one patient treated for greater than 12 months the improvement was documented by radioisotope bone imaging. It is concluded that superactive agonistic LH-RH analogues hold promise as therapeutic agents in patients with androgen-sensitive prostatic adenocarcinoma. Furthermore, the analogous of LH-RH may be used to assess the responsiveness of patients to surgical castration. Long-term administration of LH-RH analogues could become an alternative to surgical castration and estrogen therapy for the treatment of hormone-dependent prostatic carcinoma.
十名前列腺癌患者——六名处于C期，四名处于D期——接受了促黄体生成素释放激素（LH-RH）激动剂类似物治疗，疗程为6周至12个月。[D-色氨酸6]LH-RH每日皮下注射一次，剂量为100微克，[D-丝氨酸（叔丁基）6]去甘氨酰胺（10）-LH-RH乙酰胺（HOE 766）皮下注射（每日一次，50微克）或鼻内给药（每日两次，500微克）。所有患者在治疗第三周时血浆睾酮平均水平下降了75%，此后一直维持在低水平。随后，在治疗第二个月时血浆酸性磷酸酶水平下降或恢复正常，除一名患者外，所有患者在治疗第10周时血清碱性磷酸酶下降了47%。对于出现前列腺增生或尿路梗阻的C期疾病患者，有明显的临床改善。在两名此类患者中，超声检查证实前列腺体积缩小。对于以弥漫性骨转移为表现的D期疾病患者，骨痛得到缓解，一名接受治疗超过12个月的患者经放射性核素骨显像证实病情有所改善。结论是，超活性LH-RH激动剂类似物有望成为雄激素敏感性前列腺腺癌患者的治疗药物。此外，LH-RH类似物可用于评估患者对手术去势的反应性。长期使用LH-RH类似物可能成为手术去势和雌激素治疗激素依赖性前列腺癌的替代方法。
