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Rivizor (vorozole) is a new, highly potent and selective third-generation aromatase inhibitor for treatment of advanced breast cancer. In an open-label study, 30 postmenopausal women failing tamoxifen therapy received Rivizor 2.5 mg once daily until disease progression. Rivizor produced clinical benefit (partial response or no change) in 16 of 27 evaluable patients (59.3%). Five patients (18.5%) had a partial response (UICC criteria) which lasted for a median of 15 months (range 14-42.5 months), 11 patients had disease stabilization for a median of 14 months (7-24 months), and 11 patients had disease progression. Median time to first response was 3.9 months (3-27.5 months): estimated median survival time for all patients was 22.8 months (2-52.8 months) and estimated median time to disease progression was 10.8 months (1.4-42.4 months). Estradiol levels decreased to below limits of detection from 1st month of treatment until study end. Androstenedione, 17alpha-hydroxyprogesterone, dehydroepiandrosterone, and free-testosterone levels were unaffected by Rivizor. ACTH stimulation tests demonstrated that Rivizor does not interfere with adrenal mineralocorticoid and glucocorticoid steroid synthesis. Adverse events were mild-to-moderate. Rivizor might be an effective and well-tolerated alternative treatment for postmenopausal advanced breast cancer patients following tamoxifen failure.

Vorozole (Rivizor) is a potent and stereospecific inhibitor of aromatase having shown promising endocrine effects in phase I studies. In the present trial, 27 postmenopausal patients with advanced breast cancer, measurable lesions, presumably hormone responsive (ER or PR+, or ER? with disease-free survival longer than 1 year, or prior documented response to tamoxifen), were treated with vorozole one tablet 2.5 mg daily. All had been previously treated with tamoxifen as adjuvant (two patients) or for advanced disease (24 patients), or both (one patient). Objective remissions were observed in eight patients (30%) with two complete responses (CR) and six partial responses (PR) lasting for a median of 14.3 months (range 6.8-40.6); nine stabilizations were also recorded (median 7.9 months; range 3.7-40.1). Median time to progression for the 27 patients was 5.9 months. Sites of response were skin (three patients), lymph nodes (two patients), lung (two patients) and chest wall plus lymph nodes (one patient). Treatment was very well tolerated: mild hot flushes (four patients), gastrointestinal complaints (four patients) and no significant toxicity (common toxicity criteria grade above 2) or drug-related severe adverse event. It is concluded that vorozole is an active second-line endocrine treatment, deserving consideration for randomized comparison with other agents such as aminoglutethimide, megestrol acetate or medroxyprogesterone acetate.

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 4.6-0), 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.