6533b85cfe1ef96bd12bd217

RESEARCH PRODUCT

Gonadotropin-releasing hormone analogues for palliation of carcinoma of the prostate

subject

description

Since the introduction of contrasexual treatment as the basic concept of palliation of prostatic carcinoma in the 1940's, orchiectomy, estrogens, and, in recent years, antiandrogens have become generally accepted treatment forms. Three facts: 1) estrogen treatment being at best palliative and at worst dangerous; 2) surgical castration having psychological impacts, at least in the younger age group; and 3) both being probably ineffective from the beginning, have led us to investigate an alternative of minimal toxicity and possible reversibility in the initial treatment of advanced prostatic carcinoma. 12 patients with far advanced carcinoma of the prostate were treated with the gonadotropin releasing hormone analogue [D-Ser(But)6]-LH-RH(1-9)-nonapeptide ethylamide (Buserelin, Hoe 766), which caused down-regulation of pituitary luteinizing hormone (LH) receptors and suppressed testosterone to castrate levels within four weeks. The production rate of testosterone (PR-T) was lowered to values comparable to those after bilateral orchiectomy within two weeks. Subjectively, patients responded favorably with a relief of metastatic bone pain in all cases and an improvement of the Karnofsky Performance Index to an average score of 75 in those patients who had had an initially low index averaging 45. Objective responses included reduction of local tumor mass with resolution of bilateral ureteral obstruction, regression of pulmonary and bone metastases, and decrease of initially elevated serum acid phosphatase concentration. On the basis of these preliminary data, it should be expected that treatment of far advanced prostatic adenocarcinoma with gonadotropin-releasing hormone analogues is a safe, nontoxic and effective form of palliation.