Randomized phase III trial comparing the new potent and selective third-generation aromatase inhibitor vorozole with megestrol acetate in postmenopausal advanced breast cancer patients. North American Vorozole Study Group.

PURPOSE: To compare the efficacy and safety of vorozole (VOR) 2.5 mg once daily with that of megestrol acetate (MA) 40 mg four times per day as second-line therapy in postmenopausal women with advanced breast cancer whose disease progressed after tamoxifen treatment. PATIENTS AND METHODS: A total of 452 patients were enrolled onto an open, multicenter, randomized phase III trial comparing VOR to MA for tumor response, safety, and quality of life (as indicated by the Functional Living Index-Cancer score). RESULTS: Vorozole produced a response rate of 9.7%, compared with 6.8% for MA (P = .24). Clinical benefit (complete response + partial response + no change in > 6 months) was demonstrated in 23.5% and 27.2% of patients treated with VOR and MA, respectively (P = .42). Median duration of response was 18.2 months for VOR versus 12.5 months for MA (P = .074). There was no significant difference in time to progression or survival between the treatment groups. Discontinuation of treatment because of adverse events occurred less frequently in the VOR-treated group (3.1% v 6.2%; P = .18). Patients on the VOR arm reported significantly more nausea, hot flushes, arthralgia, upper respiratory tract infection, anorexia, and paresthesia, whereas those treated with MA had significantly more dyspnea, increased appetite, and weight increase. There was no difference between the two treatment groups in Functional Living Index-Cancer scores (total or subscales). However, when analyzed by objective response, patients with complete or partial responses (P = .032) or no change (P = .033) who were receiving VOR had significant improvement in the psychologic well-being subscale, compared with patients given MA. CONCLUSION: Vorozole is well tolerated and as effective as MA in the treatment of postmenopausal advanced breast cancer patients with disease progression after tamoxifen treatment.