Effects of Fadrozole (CGS 16949A) and Letrozole (CGS 20267) on the inhibition of aromatase activity in breast cancer patients

Fadrozole Hydrochloride (CGS 16949A) and Letrozole (CGS 20267), are two of the newest non-steroidal, orally active aromatase inhibitors currently being evaluated as second line treatment of patients with hormone dependent forms of metastatic breast cancer. In a phase I clinical efficacy study, we examined the ability of these two imidazole derivatives to suppress the synthesis of estrogen in a cohort of postmenopausal patients with metastatic breast cancer. Both medications at relatively low doses were potent and rapid inhibitors of aromatase activity as evidenced by their ability to suppress the level of blood and urine estradiol and estrone as well as blood estrone sulfate in these patients. Letrozole appeared to be the more potent of the two, with over 95% suppression of both plasma and urinary estrogens observed within 2 weeks of therapy. Letrozole appeared to be more selective than Fadrozole in inhibiting aromatase activity in that no compromise in cortisol and aldosterone output was evident with Letrozole therapy at all of the doses tested, a compromise clearly seen with Fadrozole. The inhibition of aromatase activity by these imidazole derivatives as second line therapy for patients with hormone dependent breast cancer appears to be a favorable alternative form of hormone ablative therapy and holds considerable promise for the treatment of this malignancy.