[Chemical castration using a depot LHRH-agonist as a palliative therapy concept in prostatic carcinoma--clinical, endocrinological and experimental studies]. / Chemische Kastration mit einem Depot LHRH-Agonisten als palliatives Therapiekonzept beim Prostatakarzinom--klinische, endokrinologische und experimentelle Untersuchungen.

79 patients with locally advanced and/or metastatic prostate cancer were treated by means of a biodegradeable depot formulation of the luteinizing hormone releasing hormone analogue Goserelin (Zoladex). All patients received 3.6 mg depot Goserelin (Zoladex 3.6 mg implantate) subcutaneously into the anterior abdominal wall at 4 weekly intervals. The average time of observation was 24.2 months. The best objective response rate was found in 62%. Serum testosterone levels initially increased after the first depot injection and then decreased ultimately to castrate range (less than 0.6 ng/ml) between day 15 and day 27 (median 21) in the majority of patients. Castrate testosterone levels were still found 48 months after the start of treatment with depot Goserelin. 6 months after institution of treatment in 66.7% of cases evident signs of histological regression were found in the primary tumour tissue. Adenocarcinoma presented with a highly significantly better response pattern than anaplastic carcinoma. In animal experiments a single dose of 1 mg depot Goserelin was administered to adult male rats and the effect on serum testosterone levels and target organs (testes and ventral prostate) were investigated. Mean testosterone levels (mean = 0.31 ng/ml) decreased to castrate range (less than 0.3 ng/ml). 4 weeks after depot injection weight of the testes and prostate weight were significantly reduced. However 8 weeks after administration of 1 mg depot Goserelin there was no significant between the control group and the treated group. We conclude that the depot formulation of Goserelin (Zoladex) is effective, simple, practicable and safe in the treatment of advanced prostatic cancer. Current clinical studies are confirming the importance of reversible medical castration by LHRH agonists before radical prostatectomy.

Effects of long term GnRH analogue treatment on hormone levels and spermatogenesis in patients with carcinoma of the prostate.

The effects of long term GnRH treatment with the biodegradable depot formulation of ICI 118.630 on hormone levels and spermatogenesis were investigated in 18 males with advanced prostate cancer. Plasma levels of FSH, LH, testosterone, DHEA-S and SHBG were monitored at regular intervals. The drug suppressed FSH, LH and testosterone significantly and did not affect DHEA-S and SHBG plasma levels. Tissue specimens for histologic assessment and quantitative analysis of germinal cell types were obtained at secondary orchidectomy in 16 patients immediately following GnRH analogue treatment. Germinal cell maturation was arrested at the spermatogonial stage. In two patients discontinuing treatment histologic assessment of secondary orchidectomy specimens 9 and 10 months after the last GnRH analogue depot injection resulted in germinal cell maturation to late spermatids in part of the tubule cross sections. These results indicate that long term administration of the GnRH analogue fails to produce complete testicular sclerosis and spermatogenic arrest might be reversible.