Vorozole results in greater oestrogen suppression than formestane in postmenopausal women and when added to goserelin in premenopausal women with advanced breast cancer

The high potency and selectivity of new aromatase inhibitors has translated to greater efficacy and improved tolerability in comparison with establish ed second-line hormonal agents for advanced breast cancer in phase III clin ical trials. Two pharmacological studies are reported which assess the use of one of these inhibitors, vorozole, in combination or comparison with wel l-established methods of oestrogen deprivation in pre and postmenopausal pa tients. When combined with the gonadotrophin-releasing hormone agonist (GnR Ha) goserelin in 10 premenopausal patients, vorozole markedly enhanced the suppression of serum levels of oestrone, oestradiol and, oestrone sulphate beyond that achieved by goserelin alone (by a mean 74%, 83%, and 89%, respe ctively). The combination was well-tolerated and had no significant effects on androgen levels. Vorozole was compared with formestane in 13 postmenopa usal women and serum oestrone, oestradiol, and oestrone sulphate levels wer e suppressed by 47%, 30%, and 70%, respectively, more by vorozole than by t he steroidal aromatase inhibitor. Again the tolerability was excellent. The plasma oestrogen levels in the postmenopausal patients on vorozole were lo wer than in the premenopausal patients on goserelin plus vorozole, indicati ng that ovarian oestrogen synthesis may be relatively resistant to aromatas e inhibition, even during GnRHa treatment. Thus, in both pre and postmenopa usal patients substantially greater suppression of oestrogen can be achieve d by vorozole compared with alternative approaches. Existing clinical-pharm acological correlates suggest that these increases in pharmacological effec tiveness may result in enhanced clinical effectiveness.