Persistent blockade of the pituitary‐gonadal axis in patients with prostatic carcinoma during chronic administration of D‐Trp‐6‐LH‐RH

Abstract

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.

Combination of a long-acting delivery system for luteinizing hormone-releasing hormone agonist with Novantrone chemotherapy: increased efficacy in the rat prostate cancer model.

“…3 (2,3,(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). The therapy based on agonists of LH-RH avoids the cardiovascular and mammotropic side effects of estrogens and the psychological impact of orchiectomy (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36). It has been suggested that treatment with [D-Trp6]LH-RH produces a higher rate of response than transcapsular orchiectomy (35).…”

“…It has been suggested that treatment with [D-Trp6]LH-RH produces a higher rate of response than transcapsular orchiectomy (35). The use of LH-RH agonists may be the method of choice for the treatment ofprostate cancer (3,(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36) been used successfully for the treatment of women with endometriosis (37) and children with precocious puberty (38). However, the duration of response and the median survival time in patients with prostate cancer cannot yet be estimated.…”

“…Recently, one patient relapsed after 18 months of objective and subjective remission in response to [DTrp6]LH-RH treatment, in spite of continued blockade of pituitary-gonadal axis, and had to be treated by chemotherapy with cyclophosphamide (34). This relapse is attributed to a selective proliferation of clones of androgen-independent cancer cells that preexisted within the heterogeneous prostate tumor (7)(8)(9).…”

Use of Luteinizing Hormone - Releasing Hormone Analogs in the Treatment of Hormone-Dependent Tumors

“…In follow-up studies, Gonzalez-Barcena and associates 45 treated 40 patients with stage D 2 prostatic carcinoma for up to 30 months with D-Trp 6 LHRH. As in the first study, the analog was given subcuta-neously once daily at a dose of 1 mg per day for the first 7 days, and subsequently the dose was reduced to 100 µg per day.…”

Blood-based LC-MS/MS analysis of steroids in prostate and ovarian cancer diagnostics

“…Between the beginning of the 1980s and the 2000s, multiple studies were performed using RIA investigating the castration efficacy of LHRH agonists (46,(118)(119)(120)(121)(122)(123)(124)(125)(126)(127) and one antagonist (128). Another study in that period investigated testosterone levels in surgically castrated prostate cancer patients (129).…”