The clinical and endocrine effects of 4-hydroxyandrostenedione alone and in combination with goserelin in premenopausal women with advanced breast cancer

Stein, Robert; Dowsett, Mitchell; Hedley, AJ; Gazet, J C; Ford, H. T.; Coombes, R. Charles

doi:10.1038/bjc.1990.356

Cited by 95 publications

(30 citation statements)

References 22 publications

(27 reference statements)

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“…Perhaps of more interest is the observation that on relapse after response to a GnRH agonist some premenopausal patients will respond to the addition of an aromatase inhibitor (in combination with the continued use of the G n R H agonist) (31). This is associated with substantially enhanced suppression of oestrogen levels and suggests that step-wise oestrogen deprivation is a useful means of hormonal therapy.…”

Section: Selection Of Agents and Patientsmentioning

confidence: 99%

Endocrine Treatment of Advanced Breast Cancer

Dowsett

1996

Acta Oncologica

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Section: Selection Of Agents and Patientsmentioning

confidence: 99%

Endocrine Treatment of Advanced Breast Cancer

Dowsett

1996

Acta Oncologica

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“…Encouraging results were obtained with a combination of 4-hydroxyandrostenedione and goserelin, the growth hormonereleasing hormone agonist currently used for medical ovariectomy. Goserelin is not able to affect peripheral aromatisation, but, in patients who respond to goserelin and then relapse, the subsequent addition of 4-hydroxyandrostenedione produces further reduction in oestradiol and subsequent response in a high proportion of patients (Stein et al 1990). Others have also studied the combination of aminoglutethimide and 4-hydroxyandrostenedione in postmenopausal patients with breast cancer.…”

Section: Second-generation Aromatase Inhibitors: 4-hydroxyandrostenedmentioning

confidence: 99%

“…A further study, carried out by our group (Stein et al 1990), indicated that a stepwise suppression of oestradiol could result in more prolonged benefit for patients with metastatic breast cancer. In this study, premenopausal patients who had achieved either disease stabilisation or remission on goserelin treatment were given 4-hydroxyandrostenedione on relapse and goserelin treatment was maintained.…”

Section: Sequential Administration Of Aromatase Inhibitorsmentioning

confidence: 99%

Aromatase inhibitors and their use in the sequential setting.

Coombes

Harper‐Wynne²,

Dowsett³

1999

Endocrine-Related Cancer

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Over the past decade several novel aromatase inhibitors have been introduced into clinical practice. The discovery of these drugs followed on from the observation that the main mechanism of action of aminogluthemide was via inhibition of the enzyme aromatase thereby reducing peripheral levels of oestradiol in postmenopausal patients.The second-generation drug, 4-hydroxyandrostenedione (formestane), was introduced in 1990 and although its use was limited by its need to be given parenterally it was found to be a well-tolerated form of endocrine therapy.Third-generation inhibitors include vorozole, letrozole, anastrozole and exemestane, the former three being non-steroidal inhibitors, the latter being a steroidal inhibitor. All are capable of inhibiting aromatase action by >95% compared with 80% in the case of 4-hydroxyandrostenedione.The sequential use of different generations of aromatase inhibitors in the same patients is discussed. Studies suggest that an optimal sequence of these compounds may well result in longer Endocrine-Related Cancer (1999) 6 259-263 remission in patients with hormone receptor positive tumours.

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“…In DMBA-induced mammary tumors we demonstrated favorable antitumor effects of combined treatment with buserelin and antiprogestins (13), while Szende et al (14) showed additional antitumor effects of LHRH and somatostatin analogues in MXT mammary tumors. Stein et al (15) observed favorable endocrine effects (a decrease in estradiol from 24 to 6 pmol/l) by adding an aromatase inhibitor (40HA) to treatment with goserelin (Zoladex).…”

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confidence: 99%