Phase II and III clinical trials of toremifene for metastatic breast cancer.

Toremifene (Fareston) received FDA approval in 1997 for the first-line treatment of postmenopausal women with estrogen receptor (ER)-positive or -unknown metastatic breast cancer. Phase II and III trials have demonstrated that first-line therapy with toremifene, 60 mg/d, is as effective and as well tolerated as tamoxifen (Nolvadex), 20 or 40 mg/d, in such patients. To date, phase III trials have failed to show a statistically significant advantage of higher toremifene doses over standard doses of tamoxifen in these women. Studies appeared to indicate minimal efficacy of high toremifene doses in women with ER-negative tumors, but the number of patients studied was small. Although results of some trials of high-dose (240 mg/d) toremifene in tamoxifen-"refractory" patients were negative, other trials that included prolonged (> or = 6 months) stable disease as an indication of clinical benefit yielded positive results.