Suppression of plasma 6-keto-prostaglandin F1α and 13,14-dihydro-15-keto-prostaglandin F2α by aminoglutethimide in advanced breast cancer

Harris, Adrian L.; Mitchell, Murray D.; Smith, IE; Powles, T. J.

doi:10.1038/bjc.1983.233

Cited by 23 publications

(8 citation statements)

References 22 publications

(16 reference statements)

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“…The response of some patients to cortisone alone (Miller & Hinman, 1954) or to bilateral adrenalectomy (Mahoney & Harrison, 1972;Hendry, 1974) suggests that in some cases the tumour may retain sensitivity to residual adrenal androgens. Aminoglutethimide is an inhibitor of several enzymes involved in adrenal steroid synthesis (Dexter et al, 1967) and in prostaglandin metabolism (Harris et al, 1983c). The combination of aminoglutethimide and hydrocortisone had previously been reported both to reduce circulating levels of adrenal androgen and, in small numbers of patients, to induce responses in hormone-relapsed advanced prostatic cancer (Robinson et al, 1974;Sanford et al, 1976).…”

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confidence: 99%

Response to aminoglutethimide and cortisone acetate in advanced prostatic cancer

Ponder¹,

Shearer²,

Pocock³

et al. 1984

Br J Cancer

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Summary Forty patients with metastatic adenocarcinoma of the prostate were evaluated for response to treatment with aminoglutethimide plus cortisone acetate. All had relapsed from or failed to respond to primary endocrine treatment with orchidectomy or stilboestrol. Nineteen patients (48%) showed subjective response, in most cases relief of bone pain. Side effects limited treatment in only 3 patients. We conclude that aminoglutethimide plus cortisone acetate is a useful addition to the treatment available for this difficult group of patients. The mechanism by which this treatment has a beneficial effect remains unclear.

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confidence: 99%

Response to aminoglutethimide and cortisone acetate in advanced prostatic cancer

Ponder¹,

Shearer²,

Pocock³

et al. 1984

Br J Cancer

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“…The drug has been reported to alleviate bone pain in patients suffering from the primary metastatic disease (Harris et al 1983) and also to relieve the bone pain in men suffering from advanced prostatic cancer (Rostom et al 1982). Aminoglutethimide has also been reported to be comparable to flurbiprofen in lowering prostaglandin metabolite levels in breast cancer patients (Harris et al 1983 The results indicate that aminoglutethimide interferes with the arachidonic acid cascade and this may be relevant to the drug's ability to relieve bone pain. As metastasis of some breast tumours has been linked to their synthesis of prostaglandins (Bennett, 1985), it is possible that the latter pathway may be an additional site for the action of aminoglutethimide.…”

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confidence: 85%

Presented at Oxford Meeting 1987

1988

British J Pharmacology

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Aminoglutethimide is a non-steroidal inhibitor of several cytochrome P-450-dependent systems and is used in the therapy of oestrogen-dependent breast cancers in postmenopausal women, where it acts as an inhibitor of aromatase. The drug has been reported to alleviate bone pain in patients suffering from the primary metastatic disease (Harris et al. 1983) and also to relieve the bone pain in men suffering from advanced prostatic cancer (Rostom et al. 1982). Aminoglutethimide has also been reported to be comparable to flurbiprofen in lowering prostaglandin metabolite levels in breast cancer patients (Harris et al. 1983 The results indicate that aminoglutethimide interferes with the arachidonic acid cascade and this may be relevant to the drug's ability to relieve bone pain. As metastasis of some breast tumours has been linked to their synthesis of prostaglandins (Bennett, 1985), it is possible that the latter pathway may be an additional site for the action of aminoglutethimide.

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“…comm. ) found in a non-randomised study that AG plus HC was significantly more beneficial than HC alone and AG is known to have other actions which may be of benefit to prostatic cancer patients such as inhibition of prostaglandin synthetase (Harris et al, 1983b), or its effects on the central nervous system (Santen et al, 1981).…”

Section: Discussionmentioning

confidence: 99%

The effects of aminoglutethimide and hydrocortisone, alone and combined, on androgen levels in post-orchiectomy prostatic cancer patients

Dowsett

Shearer²,

Ponder³

et al. 1988

Br J Cancer

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Aminoglutethimide has been used in combination with hydrocortisone in patients with advanced prostatic cancer with the rationale that it causes a 'medical adrenalectomy'. Both objective and subjective responses have been recorded. We have examined the effect of AG and HC alone and in combination on plasma androgen levels throughout the day in two studies on 11 such patients. Whilst AG combined with HC led to a significant suppression of both testosterone and androstenedione levels, the suppression with HC alone was significantly greater, indicating that any beneficial clinical effects of AG in these patients is not due to its suppression of adrenal androgen secretion.

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Suppression of plasma 6-keto-prostaglandin F1α and 13,14-dihydro-15-keto-prostaglandin F2α by aminoglutethimide in advanced breast cancer

Cited by 23 publications

References 22 publications

Response to aminoglutethimide and cortisone acetate in advanced prostatic cancer

Response to aminoglutethimide and cortisone acetate in advanced prostatic cancer

Presented at Oxford Meeting 1987

The effects of aminoglutethimide and hydrocortisone, alone and combined, on androgen levels in post-orchiectomy prostatic cancer patients

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