Drug and hormone interactions of aromatase inhibitors.

@article{Dowsett1999DrugAH,
  title={Drug and hormone interactions of aromatase inhibitors.},
  author={Mitch Dowsett},
  journal={Endocrine-related cancer},
  year={1999},
  volume={6 2},
  pages={
          181-5
        }
}
  • M. Dowsett
  • Published 1 June 1999
  • Biology
  • Endocrine-related cancer
The clinical development of aromatase inhibitors has been largely confined to postmenopausal breast cancer patients and strongly guided by pharmacological data. Comparative oestrogen suppression has been helpful in circumstances in which at least one of the comparitors has caused substantially non-maximal aromatase inhibition. However, the triazole inhibitors, letrozole and anastrozole, and the steroidal inhibitor, exemestane, all cause >95% inhibition. Comparisons between these drugs therefore… 

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References

SHOWING 1-10 OF 28 REFERENCES

POTENCY AND SELECTIVITY OF THE NON‐STEROIDAL AROMATASE INHIBITOR CGS 16949A IN POSTMENOPAUSAL BREAST CANCER PATIENTS

It is concluded that CGS 16949A is a potent oestrogen suppressant in postmenopausal patients but that its effect is not totally selective.

Combination hormonal therapy involving aromatase inhibitors in the management of women with breast cancer.

The advent of new aromatase inhibitors with greater potency, selectivity, and better tolerability has prompted a reconsideration of the combined therapy approach, with attention being focused on pharmacologic and endocrinologic clinical research.

Decreased serum concentrations of tamoxifen and its metabolites induced by aminoglutethimide.

It is concluded that this aminoglutethimide-tamoxifen interaction should be taken into account when evaluating the clinical effect of this drug combination relative to monotherapy.

In vivo measurement of aromatase inhibition by letrozole (CGS 20267) in postmenopausal patients with breast cancer.

Letrozole is therefore a highly effective inhibitor of aromatase, causing near complete inhibition of the enzyme in peripheral tissues at the doses investigated, and the falls in estrogen levels were greater than those seen with earlier generation aromat enzyme inhibitors.

Resistance of the ovary to blockade of aromatization with aminoglutethimide.

To inhibit ovarian estrogen production, various doses of AG and its highly potent D-stereoisomer were administered to premenopausal women with breast carcinoma, but at no dose level did AG consistently lower estrone and estradiol concentrations in plasma below those observed in normal menstruating women.

Endocrine and therapeutic effects of aminoglutethimide in premenopausal patients with breast cancer.

Aminoglutethimide in combination with hydrocortisone provides an effective therapy in postmenopausal advanced breast cancer patients, with response rates of 37.5--50% having been found. Treatment

Antagonism of aminoglutethimide and danazol in the suppression of serum free oestradiol in breast cancer patients.

The response rate of advanced postmenopausal breast cancer patients to treatment with aminoglutethimide + danazol was significantly worse than that with AG alone and the effect on the presumed biologically active unbound fraction of oestradiol may explain the poor clinical response rate.

Influence of anastrozole (Arimidex), a selective, non-steroidal aromatase inhibitor, on in vivo aromatisation and plasma oestrogen levels in postmenopausal women with breast cancer.

An internal consistency between the percentage aromatase inhibition and suppression of plasma oestrone sulphate was revealed and anastrozole was found to be highly effective in inhibiting in vivo aromatisation with no difference in efficacy between the two drug doses.

Endocrine and clinical effects of exemestane (PNU 155971), a novel steroidal aromatase inhibitor, in postmenopausal breast cancer patients: a phase I study.

It is concluded that exemestane is a well-tolerated aromatase inhibitor that effectively suppresses plasma and urinary estrogens in postmenopausal patients with breast cancer.

A randomised comparison of oestrogen suppression with anastrozole and formestane in postmenopausal patients with advanced breast cancer.

More effective and consistent suppression of oestradiol was achieved with anastrozole at the therapeutic dose of 1 mg once daily, orally, than with formestane at the standard dose of 250 mg every 2 weeks, intramuscularly.