Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-eight and 24 patients with advanced breast cancer were treated with Aminoglutethimide (AG) or AG + Tamoxifen (AG + TAM) from June 1984 to June 1989, respectively. Evaluated cases were 25 and 21 treated with AG or AG+TAM, respectively. Objective response was seen in 5/25 (20.0%) for AG treatment with 9, 13, 16, 20 and 31 months remission and 4/21 (19.1%) for AG + TAM treatment with 6, 7, 12 and 26 months remission. Response rate according to dominant site of metastases were 1/10 in soft tissue, 2/7 in bone, 2/7 in lung and pleura treated with AG, 1/9 in soft tissue, and 3/5 in lung treated with AG + TAM treatment. Two of the 5 responding patients in AG treatment group had prior tamoxifen treatment and 3 out of 4 responding patients in AG + TAM treatment group had prior chemoendocrine therapy with tamoxifen and FAC chemotherapy. Main toxic side effects were lethargy and/or rash, and drug discontinuation was required in 3 cases of AG treatment group and 2 cases of AG + TAM treatment group. Serial determination of serum hormone levels during AG or AG + TAM treatment revealed a decrease in estrone and an increase in androstenedione in many cases of both treatment groups. This data suggested that AG treatment may be favorable for endocrine treatment for advanced breast cancer patients, but the response to AG was not augmented by adding TAM.
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PMID:[Aminoglutethimide and aminoglutethimide+tamoxifen treatment for advanced breast cancer]. 141 9

45 women (postmenopausal or after former oophorectomy) with metastatic breast cancer resistant to tamoxifen as well as to chemo- and radiotherapy were treated with aminoglutethimide (750 mg or 1000 mg resp. daily) and hydrocortisone (40 mg daily). Treatment resulted in 33% remissions (2 CR + 13 PR) and 53% stabilizations (24 patients) besides a non-responder rate of 13% (6 patients). Side effects (mainly central sedation, possibly exanthema, seldom anorexia, but no hematotoxicity) were observed in 13 patients (29%). Duration of remission lasted for 1 to 24 months (mean duration 10,5 months) while stabilization extended for 2 to 17 months (mean duration 7,7 months). Mechanism of action by enzymatic inhibition of the adrenal steroid hormone synthesis ("medical adrenalectomy") as well as by extra-adrenal diminution of estrogens is considered in detail. Aminoglutethimide provides effective treatment in patients with generalized metastatic breast cancer followed by best outcome in cases with osseous metastases. Clinical results are presented as an approach to successful therapy of advanced breast cancer and an endocrine alternative in tamoxifen resistance as well as a therapeutic possibility in cytotoxic induced pancytopenia.
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PMID:[Aminoglutethimide therapy in advanced breast cancer]. 409 7

The aim of this study is to report on Aminoglutethimide-induced hormonal modifications in advanced breast cancer. Estradiol (E2), Testosterone (T), Dehydroepiandrosterone sulphate (DHEA(s] and Aldosterone (A) were determined before, and once every two weeks during treatment with Aminoglutethimide plus Hydrocortisone in 13 menopausal women with advanced breast cancer. The patients were selected either for their E2 and P4-receptor-positive in the original tumor or in metastases or by presenting objective clinical improvement to prior endocrine treatment. On the basis of the response to treatment the patients may be classified in two groups: 1) responders (n = 7) and 2) non-responders. No significant modifications of T concentrations were obtained in group 1 until after the first 8 months of treatment. One spontaneous menopausal patient with a T basal value of 0.80 ng/ml was evaluated during 12 months of treatment. From month 8, T diminished to values below 0.30 ng/ml, indicating a direct action of Aminoglutethimide, hydrocortisone or both drugs on ovarian steroidogenesis. The results obtained from the remaining hormonal parameters, evaluated in all the cases beginning from the second week of treatment, remained unchanged throughout the entire period of study. They were as follows: 1) E2 diminished with respect to basal values between 36 and 60%, thus confirming Aminoglutethimide inhibitory effect upon peripheral aromatization; 2) DHEA(s) diminished between 80 and 90%, indicating an adrenal inhibition due to the combined effect of both drugs, and 3) Aldosterone diminished to values between 80 and 110 pg/ml, these values being within the normal lower range.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preliminary study of hormone determinations during aminoglutethimide therapy for advanced breast cancer. 623 71

Aminoglutethimide inhibits steroid synthesis by the adrenal gland and the peripheral conversion of androgens to estrogens. As such it has been recommended in the place of adrenalectomy for the treatment of advanced breast cancer. Aminoglutethimide with hydrocortisone was given to 19 women with metastatic cancer of the breast whose disease was progressive, who would otherwise have undergone adrenalectomy and whose potential for response was good. Four patients could not tolerate the drug and seven failed to respond. Eight women had an objective response, complete in two and partial in four. In two patients the disease stabilized. The period of treatment ranged from 11 to 26 months but three patients are still on treatment after 26 months. The authors conclude that aminoglutethimide has a place in the management of women with advanced breast cancer who satisfy the criteria for hormone manipulation.
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PMID:Is aminoglutethimide an alternative to adrenalectomy for metastatic carcinoma of the breast? 713 30

Aminoglutethimide (Elipten), at a dosage between 250 and 1500 mg/d by mouth, was administered in a clinical phase II study to 17 patients with metastasizing carcinoma of the breast resistant to hormones and cytostatic drugs. Results of this treatment were available for 14 patients. Nine women were given the drug alone, eight in combination with cytostatic drugs. In 11 women the drug significantly decreased pain within 3-14 days. Used alone aminoglutethimide produced objective regression of the metastases in two women, two further instances of regression occurred when the drug was combined with cytostatic agents. Five women developed urticarial rash, while six had somnolence and nausea or lethargy. Aminoglutethimide is suitable for symptomatic treatment of metastasizing treatment-resistant carcinoma of the breast, either alone or in combination with cytostatic drugs.
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PMID:[Aminoglutethimide in metastasizing carcinoma of the breast resistant to hormonal and cytostatic treatment (author's transl)]. 727 74

Aromatase inhibition is now an acknowledged second line treatment modality for advanced breast cancer in postmenopausal women. Aminoglutethimide is an inhibitor of adrenal steroid biosynthesis and blocks the conversion of cholesterol to pregnenolone, and therefore reduces levels of adrenal androgens, which are a source of estrogens in both premenopausal and postmenopausal women. Aminoglutethimide has produced antitumor response rates of 35% in unselected patients, most of whom have undergone prior therapy with either chemotherapy or hormonal manipulation. As is true of other hormonal responses, high response rates of up to 70% are observed in patients who are ER and/or PR positive. The reason why these drugs are currently used after tamoxifen is mainly due to the side effects of aminoglutethimide, which impairs the mineralocorticoid and glucocorticoid synthesis. New, less toxic compounds appear, which block the conversion of androstenedione to estrone and efficiently suppress plasma estrogen levels., e.g. formestane, anastrozole and letrozole. Aromatase inhibitors are now being compared to tamoxifen as first-line endocrine treatment in relapsing patients. If these trials confirm a similar or better response rate to new aromatase inhibitors compared to tamoxifen, the time will come to study them as the first line adjuvant treatment in non-metastatic disease.
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PMID:[Aromatase inhibitors--new possibilities in treatment of breast carcinoma]. 962 25