Tamoxifen versus aminoglutethimide in advanced breast carcinoma: a randomized cross-over trial.

Smith, Ian; Harris, Adrian L.; Morgan, M.; Ford, H. T.; Gazet, J C; Harmer, C.; White, Harvey; Parsons, C.; Villardo, A; Walsh, Geraldine; McKinna, J A

doi:10.1136/bmj.283.6304.1432

Cited by 145 publications

(40 citation statements)

References 6 publications

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“…A non-significant difference in response rate in favor of adrenalectomy was obtained. A rate of response in the order of 30-35% has been found, regardless of whether treatment has been tamoxifen, aminoglutethimide and hydrocortisone (20,41), estrogens (2, 10, 13,22,33,42), medroxyprogesterone acetate (MPA) (3, 8, 9, 21, 30, 34,40,48) or megestrole acetate (MA) (6,14,24,27). In the 3 trials analyzing the relative efficacy of androgens vs. tamoxifen (17,28,51) there is a trend towards a lower response rate for patients treated with androgens as first line endocrine therapy.…”

Section: Eecacy Of Endocrine Therapymentioning

confidence: 99%

Endocrine Therapy of Advanced Breast Cancer

Rose

Mouridsen

1988

Acta Oncologica

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Section: Eecacy Of Endocrine Therapymentioning

confidence: 99%

Endocrine Therapy of Advanced Breast Cancer

Rose

Mouridsen

1988

Acta Oncologica

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“…These patients all had progressing disease and had been entered into a phase II study of AG in advanced breast cancer (Harris et al, 1982), a randomised study of tamoxifen versus AG (Smith et al, 1981) or a study of incremental dose AG (Harris et al, 1982b …”

Section: Methodsmentioning

confidence: 99%

Aminoglutethimide induced hormone suppression and response to therapy in advanced postmenopausal breast cancer

Harris¹,

Dowsett²,

Smith³

et al. 1983

Br J Cancer

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Summary Eighty-one postmenopausal women with advanced breast cancer were studied for the effects of treatment with aminoglutethimide (AG) plus hydrocortisone on peripheral hormones and response to therapy. There were 40 responders (R) and 41 non-responders (NR) at 3 months from the start of treatment. Plasma oestrone concentrations were higher in non-responders at 1 and 2 months after starting AG (Means: NR 106+50, R 84+26pmoll1-, P<0.05; highest value NR 121+51, R 99+24pmoll1, P<0.05). High oestrone levels were correlated with bulky liver secondaries, but not with age, tumour-free interval, time from last menstrual period, time from relapse to start of AG or body weight. Non-responders had higher mean prolactin levels on treatment (prolactin

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“…An Aminoglutethimide (AG) in combination with hydrocortisone (HC) is an effective endocrine therapy in advanced postmenopausal breast cancer, producing a response rate and duration similar to tamoxifen (Smith et al, 1981). AG was introduced into the treatment of breast cancer as an inhibitor of adrenal steroid production.…”

mentioning

confidence: 99%

Endocrine effects of low dose aminoglutethimide alone in advanced postmenopausal breast cancer

Harris¹,

Dowsett²,

Smith³

et al. 1983

Br J Cancer

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Summary The site of action of aminoglutethimide (AG) has been investigated. An Aminoglutethimide (AG) in combination with hydrocortisone (HC) is an effective endocrine therapy in advanced postmenopausal breast cancer, producing a response rate and duration similar to tamoxifen (Smith et al., 1981). AG was introduced into the treatment of breast cancer as an inhibitor of adrenal steroid production. One site of action is the earliest step in the adrenal conversion of cholesterol to pregnenolone (20,22 desmolase) (Dexter et al., 1967). AG treatment regimes are currently designed to inhibit this step and HC is added in replacement doses to prevent a reflex rise in ACTH secretion (Santen et al., 1974). However, AG has another site of action, the inhibition of the conversion of androgens to oestrogens in peripheral tissues tissues (Figure 1), which is the main source of oestrogen in the postmenopausal woman . AG can also inhibit 1 1-fJ-hydroxylase (Faglia et al., 1971).One of the factors limiting the use of AG is the side effects that occur at conventional dose levels (250mg 4 times a day). In one series of 190 patients, 58% had transient side effects, 9.5% needed to reduce the dose and 5% discontinued the drug (1977). Graves & Salhanick (1979) showed that aromatisation in vitro is at least 10 times more sensitive than desmolase to inhibition by AG. We have therefore studied the site of action of AG in postmenopausal patients with advanced breast cancer receiving AG and HC therapy in conventional doses and investigated the endocrine effects of low doses of AG alone. Patients and methods Synacthen testsTen postmonopausal patients with advanced breast cancer, who were taking AG 250mg 4 x daily and hydrocortisone 20mg b.d. (8am, 8pm), were studied after 3 months of therapy. Tetracosactrin (250,pg; Synacthen, Ciba) was given i.m. in the gluteus maximus. The patient was resting before the injection and for 30min afterwards. Blood samples were taken before and 30min after the injection.These tests were performed to assess the need for cortisol replacement during stress, but oestrone, dehydroepiandrosterone sulphate (DHA-S), A4 androstenedione and 17 OH progesterone were also measured.A normal cortisol response was considered to be an initial cortisol level > 138 nM I-1 and a rise of 2 200 nM 1-, with a plasma level of 2 500 nM 1 at 30 min, irrespective of initial levels.

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Tamoxifen versus aminoglutethimide in advanced breast carcinoma: a randomized cross-over trial.

Abstract: Improved diagnostic accuracy of a modified oral pancreatic function test. ScandJ3 Gastroenterol 1979 ;14 :737-41. 1 O'Donnel MD, Fitzgerald 0, McGeeney KF. Differential serum amylase determination by use of an inhibitor, and design of a routine procedure.

Cited by 145 publications

References 6 publications

Endocrine Therapy of Advanced Breast Cancer

Endocrine Therapy of Advanced Breast Cancer

Aminoglutethimide induced hormone suppression and response to therapy in advanced postmenopausal breast cancer

Endocrine effects of low dose aminoglutethimide alone in advanced postmenopausal breast cancer

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