Clinical efficacy and endocrine activity of vorozole in postmenopausal breast cancer patients. Results of a multicentric phase II study

Summary Background: Aminoglutethimide was the first aromatase inhibitor to be used successfully in breast cancer patients. However, this drug also inhibits mineralcorticoid and glucocorticoid synthesis, making co-medication with corticosteroids necessary, and it is often poorly tolerated. The primary objective of this trial was to evaluate the clinical efficacy and tolerability of vorozole, a new non-steroidal oral aromatase inhibitor, in postmenopausal breast cancer patients. The secondary objective was to evaluate the pharmacodynamic activity of the drug. Subjects and methods: Thirty-four postmenopausal patients previously treated with tamoxifen in the adjuvant setting and/ or for advanced disease were treated with vorozole, 2.5 mg once daily. Patients were monitored with respect to treatment efficacy and safety. Hormonal evaluations were performed at baseline and during the course of treatment in order to evaluate the pharmacodynamic efficacy and safety of vorozole. Results: According to UICC criteria, there were seven responders, one complete and six partial, for an overall response rate of 21% (95% confidence interval (CI) 9%-38%). The median duration of response was 9.6 months (95% CI 4.60), the median time to progression for the entire group was 4.7 months (95% CI 2.9-6.6) and the median survival time was 29.7 months (95% CI 19.1-0). Tolerability was excellent to good in 97% of the patients. Oestradiol and oestrone levels were suppressed to the limit of detection of the assays used. No effect was observed on the other endocrine parameters. Conclusions: Our results suggest that vorozole is an effective and safe drug for the treatment of advanced postmenopausal breast cancer following tamoxifen failure.