Forty patients with stage D2 prostatic carcinoma were treated for up to 30 months with D-Trp-6-LH-RH. The analog was given s.c. once daily at a dose of 1 mg/day for the first 7 days. Subsequently, the dose was reduced to 100 micrograms/day. In follow-up studies, 30 men continued this therapy for up to 24 months. Blood samples were taken before the injection of the analog and 1, 2, 4, and 6 hours later. Serum LH, FSH, and testosterone levels were measured by RIA every month for 2 years. The initial administration of 1 mg D-Trp-6-LH-RH caused a marked elevation of LH and FSH, which lasted more than 24 hours. However, 1 month later and throughout the therapy, the basal values of LH and FSH were below the normal range and no increase in serum gonadotropins levels was obtained after administration of the analog. Initial plasma testosterone was within normal limits, but during treatment with D-Trp-6-LH-RH it fell to castration levels, and no increases were seen during the 6 hours following the injection of the analog. These results show that chronic administration of D-Trp-6-LH-RH, at the doses used, blocks the pituitary-gonadal axis and that the escape phenomenon from the effects of the LH-RH agonists-induced blockade does not occur under our conditions in contrast to observations of Kerle et al with the I.C.I. Analog 118630 (8). The accumulated results reinforce the view that long-term therapy with agonists of LH-RH is the preferred alternative to surgical castration or therapy with estrogens in men with metastatic prostate cancer.

A study was done on 30 patients with advanced adenocarcinoma of the prostate treated with diethylstilbestrol. Three groups of patients were given daily doses of 1, 5, and 1 times 3 mg. diethylstilbestrol, respectively. The study was confined to the effects of treatment on the levels of plasma testosterone by taking hormonal specimens every 4 hours for 24 hours. The results showed little difference of plasma testosterone among the groups under study and a statistical analysis showed no significant differences. Therefore, our study showed no appreciable advantage in the dosage spread over the day, compared to commonly used doses of 1 or 5 mg. diethylstilbestrol given in a single dosage.