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

Purpose: to compare the efficacy and safety of vorozole (VOR) 2.5 mg once d aily with that of megestrol acetate (MA) 40 mg four times per day as second -line therapy in postmenopausal women with advanced breast cancer whose dis ease progressed after tamoxifen treatment, Patients and Methods: A total of 452 patients were enrolled onto an open, m ulticenter, randomized phase III trial comparing VOR to MA for tumor respon se, safety, and quality of life (as indicated by the Functional Living Inde x-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 c hange in > 6 months) was demonstrated in 23.5% and 27.2% of patients treate d 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 sign ificant difference in time to progression or survival between the treatment groups. Discontinuation of treatment because of adverse events occurred le ss 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, up per respiratory tract infection, anorexia, and paresthesia, whereas those t reated with MA had significantly more dyspnea, increased appetite, and weig ht increase. There was no difference between the two treatment groups in Fu nctional Living Index-cancer scores (total or subscales). However, when ana lyzed by objective response, patients with complete or partial responses (P = .032) or no change (P = .033) who were receiving VOR had significant imp rovement in the psychologic well-being subscale, compared with patients giv en MA. Conclusion:Vorozole is well tolerated and as effective as MA in the treatme nt of postmenopausal advanced breast cancer patients with disease progressi on after tamoxifen treatment. J Clin Oncol 17:52-63. (C) 1999 by American Society of Clinical Oncology.