Ten patients with prostatic carcinoma six with stage C and four with stage D disease-were treated for 6 weeks to 12 months with agonistic analogues of luteinizing hormone-releasing hormone (LH-RH). [D-Trp6JLH-RH was given subcutaneously once daily at a dose of 100 ,ug and [D-Ser(But)6des-Gly-NH210-LH-RH ethylamide (HOE 766) was given subcutaneously (50 Mg once daily) or intranasally (500 Mug twice daily). In all patients, mean plasma testosterone levels showed a 75% suppression by the third week of treatment and remained low thereafter. This was followed by a decrease or normalization of plasma acid phosphatase levels by the second month of treatment and a 47% decrease in serum alkaline phosphatase by the 10th week of treatment in all but one 'patient. In patients with stage C disease presenting with prostatism or urinary outflow obstruction, there was a noticeable clinical improvement. In two such patients, a decrease in the size of the prostate was confirmed by ultrasonography. In patients with stage D disease manifested by diffuse bone metastases, there was relief of bone pain, and in one patient treated for >12 months the improvement was documented by radioisotope bone imaging. It is concluded that superactive agonistic LH-RH analogues hold promise as therapeutic agents in patients with androgen-sensitive prostatic adenocarcinoma. Furthermore, the analogues ofLH-RH may be used to assess the responsiveness ofpatients to surgical castration. Long-term administration ofLH-RH analogues could become an alternative to surgical castration and estrogen therapy for the treatment of hormone-dependent prostatic carcinoma.There is much evidence that acute administration ofsuperactive analogues of luteinizing hormone-releasing hormone (LH-RH) causes a prolonged release of pituitary gonadotropins, which leads to stimulation of Leydig cell function and an increase in plasma testosterone (T) concentrations (1-8). Chronic administration of large doses of superactive analogues of LH-RH results in suppression of both pituitary, and Leydig cell function in animals and men (1,2,4,5,7,(9)(10)(11)(12)(13)(14)(15)(16). This paradoxical antigonadal effect of superactive analogues of LH-RH can result in regression ofboth mammary and prostatic endocrine-dependent tumors in experimental animals (17, 18). The present report describes the results of administration of two synthetic superactive long-acting LH-RH analogues, LH-RH and [D-Ser(But)6]des-Gly-NH210-LH-RH ethylamide (HOE 766), to 10 patients with prostatic.carcinoma. PATIENTS, METHODS, AND MATERIALSPatients. Ten patients with biopsy-proven prostatic adenocarcinoma were studied. Six presented with signs ofprostatism and two of the six had urinary outflow obstruction requiring frequent catheterization. None ofthese six patients (Cl, C2, C3, C4, C5, C6; 75, 70, 63, 79, 79, and 81 years old, respectively) had evidence of metastasis and therefore were classified as having stage C disease. The four other patients (D1, D2, D3, D4; 65, 71, 78, and 63 years old, respectively) pre...

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