Shimazaki J, Fuse H, Akimoto S, Sumiya H, Akakura K, Ichikawa T
Dept. of Urology, School of Medicine, Chiba University.
Gan To Kagaku Ryoho. 1988 Apr;15(4 Pt 2-1):909-16.
Endocrine therapy, which consists of orchiectomy followed by administration of large doses of estrogen, then a reduced amount of estrogen, has been applied as the main treatment for stage D2 prostatic cancer. Alternatively, anti-androgen is used for elderly patients or those with cardiovascular disorders. Survival rate with endocrine therapy at 5 and 10 years was 35% and 16%, respectively. Therefore, in Japan, a better survival is shown than that reported in western countries using much smaller doses of estrogen. Most of the side effects caused by estrogen are not serious. Side effects caused by anti-androgen are few except for loss of libido. At the start of treatment, more than 80% of patients showed a response, but gradually relapse occurred and only 20% were well controlled 5 years after the start. Factors influencing the survival were pathological grade, response to endocrine therapy judged by the level of prostatic acid phosphatase 4 weeks after the start, and R1881 (methyltrienolone)-binding protein observed histochemically. The latter protein was also correlated with the grade and response to endocrine therapy. Relapse after endocrine therapy might be attributable to adaptation or mutation progressing to androgen-independent cells. Using SC 115, an androgen-dependent mouse tumor, these two types of relapse were demonstrated. Gradual progression to undifferentiated cancer was noticed between pretreatment biopsy and autopsy. Relapse in human prostatic cancer may thus be partly due to genetic change to a resistant clone.
内分泌治疗，包括睾丸切除术，随后给予大剂量雌激素，然后减少雌激素用量，已被用作D2期前列腺癌的主要治疗方法。或者，抗雄激素药物用于老年患者或患有心血管疾病的患者。内分泌治疗5年和10年的生存率分别为35%和16%。因此，在日本，使用小得多剂量的雌激素所显示的生存率比西方国家报道的要好。雌激素引起的大多数副作用并不严重。除性欲丧失外，抗雄激素药物引起的副作用很少。在治疗开始时，超过80%的患者有反应，但逐渐出现复发，开始治疗5年后只有20%的患者得到良好控制。影响生存的因素包括病理分级、开始治疗4周后根据前列腺酸性磷酸酶水平判断的内分泌治疗反应，以及通过组织化学观察到的R1881（甲基三烯olone）结合蛋白。后一种蛋白也与分级和内分泌治疗反应相关。内分泌治疗后的复发可能归因于向雄激素非依赖细胞的适应或突变进展。使用雄激素依赖的小鼠肿瘤SC 115，证明了这两种类型的复发。在治疗前活检和尸检之间注意到向未分化癌的逐渐进展。因此，人类前列腺癌的复发可能部分归因于向耐药克隆的基因改变。
