Clinical effect of aminoglutethimide, medical adrenalectomy, in treatment of 43 patients with advanced prostatic carcinoma.

The initial treatment of patients with Stage D prostatic carcinoma with orchiectomy or estrogens is successful in giving objective and subjective improvement for variable periods of time. However, after initial endocrine treatment patients generally relapse, and go on to further progression of their disease. However, a subgroup of approximately 22% of these Stage D prostatic cancer patients respond to either surgical adrenalectomy or hypophysectomy, indicating some degree of continued hormonal responsiveness.

Suppression of residual oestrogen production with aminoglutethimide in women following surgical hypophysectomy or adrenalectomy.

In postmenopausal women with breast carcinoma, plasma and urinary oestrogens remain detectable following surgical adrenalectomy or hypophysectomy. These residual oestrogens could result from absorption of exogenous steroids, from endogenous production, or from a combination of these two sources. To determine whether endogenous production contributes to this oestrogen pool, we administered a potent steroidogenesis inhibitor, aminoglutethimide (AG), to women with breast carcinoma following hypophysectomy or adrenalectomy.

Effect of very high dose D-leucine6-gonadotropin-releasing hormone proethylamide on the hypothalamic-pituitary testicular axis in patients with prostatic cancer.

Potent synthetic analogs of gonadotropin-releasing hormone produce parodoxical antireproductive effects when administered chronically. These compounds are minimally toxic and may exhibit no plateau of the dose-response curve even at very high doses. These considerations served as the basis for our systematic evaluation of [D-leucine6-desarginine-glycine-NH2(10)]gonadotropin-releasing hormone (GnRH-A) proethylamide in the very high dose range (i.

Clinical and biochemical effect of aminoglutethimide in the treatment of advanced prostatic carcinoma.

Treatment of male patients with advanced prostatic carcinoma and disease progression after initial endocrine therapy frequently is unsatisfactory. However, approximately 20 per cent of these patients respond to surgical adrenalectomy or hypophysectomy, indicating continued hormonal responsiveness. A total of 25 previously castrated men with stage D carcinoma received 1,000 mg.

Adequacy of estrogen suppression with aminoglutethimide and hydrocortisone as treatment of human breast cancer: correlation of hormonal data with clinical responses.

Human breast neoplasms can be divided into hormone-dependent and hormone-independent subtypes. Estrogen is the major hormonal stimulus for growth of the dependent tumors. Failure to respond to estrogen suppression therapy could reflect either an incomplete lowering of estrogens or the hormonal independence of the tumor.

Plasma estrone-sulfate: assessment of reduced estrogen production during treatment of metastatic breast carcinoma.

Highly sensitive and specific estrogen assays are required to monitor the hormonal effects of surgical adrenalectomy or pharmacologic estrogen suppression in postmenopausal women with breast carcinoma. Because the levels of plasma estrone-sulfate are 10-fold higher than its unconjugated counterpart, we developed a radioimmunoassay for estrone-sulfate to quantitate the minimal estrogen concentrations expected under conditions of endocrine gland ablation. After establishing normal ranges, we compared plasma estrone- sulfate levels and urinary conjugated estrone basally and after surgical adrenalectomy or aminoglutethimide (estrogen suppression) therapy in 23 postmenopausal women with breast carcinoma.

Aminoglutethimide as treatment of postmenopausal women with advanced breast carcinoma.

Hormone-dependent breast carcinomas respond to deprivation of biologically active estrogens with objectively quantifiable tumor regression. Aminoglutethimide, a known inhibitor of steroid synthesis, is also a potent blocker of the aromatase enzyme and, thus, of estrogen production. We developed an effective regimen to inhibit estrogen production in postmenopausal women using aminoglutethimide and replacement glucocorticoid.

How effective is surgical adrenalectomy in lowering steroid hormone concentrations?

Surgical adrenalectomy produces objective tumour regression in 50-60% of estrogen receptor-positive women with metastatic breast carcinoma. Additional responses to antiestrogens or further suppression of estrogens with aminoglutethimide after adrenalectomy suggest the possibility of continued adrenal steroid secretion even after surgical ablation. The use of sensitive and specific RIAs allows precise determination of the degree of hormone suppression after adrenalectomy and could provide documentation of nonsuppression or escape from suppression in individual patients.

Triple drug chemotherapy in treatment of prostate adenocarcinoma Nb Pr A.I.-III.

The combination of cyclophosphamide, cis-platinum, and adriamycin has been evaluated in the Nb tumor model system. Triple drug therapy has resulted in marked reduction in tumor volume (P less than 0.01), as well as decreased number of metastases (P less than 0.

Recovery of hypothalamic-pituitary-adrenal function after long term suppression by aminoglutethimide and hydrocortisone.

Little data are available concerning recovery of adrenal function after prolonged inhibition of steroidogenesis by enzyme inhibitors. Aminoglutethimide (AG), a potent blocker of adrenal steroid biosynthesis, combined with physiological replacement doses of hydrocortisone (HC) is currently being used to treat women with metastatic breast carcinoma. We studied the time-course of recovery of hypothalamic-pituitary-adrenal function after prolonged drug therapy in 10 women.

A randomized trial comparing surgical adrenalectomy with aminoglutethimide plus hydrocortisone in women with advanced breast cancer.

We randomized 96 postmenopausal women with metastatic breast carcinoma to receive surgical adrenalectomy or medical therapy with an adrenal inhibitor, aminoglutethimide (AG), plus replacement hydrocortisone. Before randomization, women were stratified according to disease-free interval, site of dominant disease, and estrogen-receptor status. Of 40 evaluable women treated with AG and hydrocortisone, 53 per cent had objective responses, as compared with 45 per cent of 29 women undergoing surgical adrenalectomy (P value not significant).

Evidence that brain aromatization regulates LH secretion in the male dog.

A variety of data suggest an independent role for androgens and estrogens in the regulation of luteinizing hormone (LH) secretion in the male. Estrogens, in the male are primarily derived from testicular androgens that are aromatized both in peripheral tissues and in the CNS. Our prior data suggested a pharmacologic regimen that blocked CNS aromatization without lowering peripheral estrogen or testosterone levels.

A possible role of endogenous opioids in the control of prolactin and luteinizing-hormone secretion in the human.

We investigated the participation by endogenous opioid peptides in the control of prolactin and gonadotropin secretion in 5 normal men and 6 normal women, and in 4 men and 5 women with persisting hyperprolactinemia following transsphenoidal pituitary microsurgery for prolactinomas. Iv administration of the specific opiate-receptor antagonist, naloxone hydrochloride (0.2 mg/kg bolus), failed to affect serially sampled serum prolactin levels in normal male or female subjects.

Therapy for Nb rat tumor transplanted in athymic mice.

Two Nb rat prostatic adenocarcinomas, 13 Pr-12, an autonomous tumor, and 2 Pr-128, an androgen-dependent tumor, were transplanted into groups of congenitally athymic nude mice. The agents used for treatment of these tumors are agents characteristically not used in treatment of prostatic adenocarcinoma in humans. However, these have been efficacious in treating other solid malignancies.

Treatment of an Nb-Pr-A.I.-3 (autonomous) tumor with combination chemotherapy.

The rat prostatic adenocarcinoma Nb-Pr-A.I.-3, an androgen-insensitive tumor, was evaluated with the following treatments: cyclophosphamide, cis-platinum, adriamycin, and the following combination therapies: cyclophosphamide and cis-platinum; adriamycin and cis-platinum; adriamycin, cis-platinum, and cyclophosphamide.

Combination chemotherapy in a prostate tumor model: Nb rat prostatic adenocarcinoma model.

This report presents the experience with single and combination chemotherapy in the Noble rat prostatic adenocarcinoma model. The best single agent in treatment of these tumors is cyclophosphamide, the best combination was triple drug therapy cyclophosphamide, cis-platinum, and adriamycin. This report examines the effect of the various chemotherapeutic regimens on tumor volume, number of metastasis, and complete tumor regression.

Evaluation of methods for perfusing rat testes.

Organ perfusion methods offer a number of advantages in biologic studies but require full characterization before application. Two new methods for perfusing rat testes were characterized and compared with recirculating hemicorpus system. These preparations, selective and isolated testicular perfusion, are nonrecirculating and consequently, allow direct measurement of testosterone secretion.