摘要
Purpose: Goserelin suppresses ovarian function, but does not inhibit oestrogen production in peripheral tissues. Therefore addition of the aromatase inactivator exemestane may optimally decrease oestrogen levels. The combination of goserelin and exemestane may therefore be useful in the adjuvant treatment of primary breast cancer. The climacteric symptoms expected with this regimen may be relieved by tibolone. Material and Methods: The 24- week, open, randomised, multicentre ADAGIO (Adjuvant Aromasin combined with Goserelin) pilot study was conducted in 48 premenopausal women (aged 35- 55 years)- with histologically confirmed oestrogen and/or progesterone receptor- positive, node negative primary breast cancer (pT1, M0 [grade 1- 2]) of low or intermediate risk. Patients were randomised to one of four groups: goserelin 3.6 mg depot implanted s.c. every 28 days; goserelin plus oral exemestane 25 mg/day; goserelin plus oral tibolone 2.5 mg/day; or goserelin plus exemestane and tibolone. Results: There was a rapid fall in serum oestradiol, oestrone and oestrone sulphate to postmenopausal levels in all four treatment groups; there were no significant differences between the groups. LH and FSH were also suppressed. Climacteric symptoms increased in intensity in all groups, although patients receiving tibolone had significantly fewer hot flushes (p < 0.01), sleep disorders (p < 0.05), loss of libido (p < 0.01) and vaginal dryness (p < 0.05). The combination of goserelin and exemestane did not reduce bone mineral density (BMD) more than goserelin alone. There was a trend towards a protective effect of tibolone on BMD. There were no significant differences in adverse events between the four groups and no serious adverse events were observed. Conclusions: Combination treatment with goserelin and exemestane is as safe and well tolerated as standard treat ment with goserelin alone. The addition of tibolone reduces the severity of some climacteric symptoms and may also reduce bone loss.
Purpose: Goserelin suppresses ovarian function, but does not inhibit oestrogen production in peripheral tissues. Therefore addition of the aromatase inactivator exemestane may optimally decrease oestrogen levels. The combination of goserelin and exemestane may therefore be useful in the adjuvant treatment of primary breast cancer. The climacteric symptoms expected with this regimen may be relieved by tibolone. Material and Methods: The 24- week, open, randomised, multicentre ADAGIO (Adjuvant Aromasin combined with Goserelin) pilot study was conducted in 48 premenopausal women (aged 35- 55 years)- with histologically confirmed oestrogen and/or progesterone receptor- positive, node negative primary breast cancer (pT1, M0 [grade 1- 2]) of low or intermediate risk. Patients were randomised to one of four groups: goserelin 3.6 mg depot implanted s.c. every 28 days; goserelin plus oral exemestane 25 mg/day; goserelin plus oral tibolone 2.5 mg/day; or goserelin plus exemestane and tibolone. Results: There was a rapid fall in serum oestradiol, oestrone and oestrone sulphate to postmenopausal levels in all four treatment groups; there were no significant differences between the groups. LH and FSH were also suppressed. Climacteric symptoms increased in intensity in all groups, although patients receiving tibolone had significantly fewer hot flushes (p < 0.01), sleep disorders (p < 0.05), loss of libido (p < 0.01) and vaginal dryness (p < 0.05). The combination of goserelin and exemestane did not reduce bone mineral density (BMD) more than goserelin alone. There was a trend towards a protective effect of tibolone on BMD. There were no significant differences in adverse events between the four groups and no serious adverse events were observed. Conclusions: Combination treatment with goserelin and exemestane is as safe and well tolerated as standard treat ment with goserelin alone. The addition of tibolone reduces the severity of some climacteric symptoms and may also reduce bone loss.
