The high potency and selectivity of new
aromatase inhibitors has translated to greater efficacy and improved tolerability in comparison with established second-line hormonal agents for advanced
breast cancer in phase III clinical trials. Two pharmacological studies are reported which assess the use of one of these inhibitors,
vorozole, in combination or comparison with well-established methods of oestrogen deprivation in pre and postmenopausal patients. When combined with the gonadotrophin-releasing
hormone agonist (GnRHa)
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%, respectively). The combination was well-tolerated and had no significant effects on androgen levels.
Vorozole was compared with
formestane in 13 postmenopausal women and serum oestrone,
oestradiol, and
oestrone sulphate levels were suppressed by 47%, 30%, and 70%, respectively, more by
vorozole than by the steroidal
aromatase inhibitor. Again the tolerability was excellent. The plasma oestrogen levels in the postmenopausal patients on
vorozole were lower than in the premenopausal patients on
goserelin plus
vorozole, indicating that ovarian oestrogen synthesis may be relatively resistant to
aromatase inhibition, even during GnRHa treatment. Thus, in both pre and postmenopausal patients substantially greater suppression of oestrogen can be achieved by
vorozole compared with alternative approaches. Existing clinical-pharmacological correlates suggest that these increases in pharmacological effectiveness may result in enhanced clinical effectiveness.