Gonadotropin‐releasing hormone agonistic analogues in the treatment of advanced prostatic carcinoma

Abstract

Orchiectomy or chronic administration of the gonadotropin releasing hormone agonistic analogue D, Ser (TBU)⁶, des Gly-NH₂¹⁰ ethylamide (HOE 766) were employed as therapeutic maneuvers in 25 patients with advanced prostatic carcinoma. HOE 766 administration effectively suppressed plasma testosterone to castrate levels that persisted for as long as treatment continued. Surgical and medical castration resulted in a significant decrease in prostatic size; this became evident earlier for surgically than medically treated patients (P <.05), but no difference existed after the third month of treatment. Symptoms and signs of prostatism improved in practically all the patients. Among patients with stage D₂ disease, there was an improvement in five as far as bone radiological assessment was concerned. Alkaline phosphatase levels did not show appreciable changes in patients showing objective stable disease or partial response according to National Prostatic Cancer Project criteria. Radioimmunoassayable prostatic acid phosphatase levels became normal in two of two stage C, five of five stage D₁, and eight of seventeen patients with stage D₂ disease, a rise in prostatic acid phosphatase (PAP), in alkaline phosphatase, and deterioration in bone radiology were associated with clinical evidence of relapse; this occured despite persistently low levels of plasma testosterone. Serum thyroxine, cortisol, and prolactin levels remained unchanged following orchiectomy or chronic administration of HOE 766. Practically all patients complained of hot flashes and experienced a decrease in libido and potency, but none developed gynecomastia or thromboembolic episodes. The data indicate that HOE 766 can be used safely as an alternative to castration or estrogens for the treatment of patients with androgen-dependent prostatic cancer.