High-dose toremifene vs tamoxifen in postmenopausal advanced breast cancer

To compare the efficacy and safety of high doses (200 or 240 mg/d) of toremifene (Fareston) to standard doses (20 or 40 mg/d) of tamoxifen (Nolvadex) in postmenopausal women with estrogen receptor (ER)-positive or ER-unknown advanced breast cancer, we pooled data from two randomized, three-arm clinical trials. Of the 733 patients included in the overview, 369 were randomized to high-dose toremifene and 364, to tamoxifen. At median follow-up of 19 months, disease had progressed in over 70% of the patients. Response rates were 25.2% in the high-dose toremifene arm and 19.8% in the tamoxifen arm (P = .087). The two treatments appeared to be statistically equivalent with respect to risk for disease progression and survival. Reversible SGOT elevation was observed in 26 tamoxifen-treated patients vs 64 high-dose toremifene recipients (P < .001) and nausea in 33 vs 50 patients (P = .085). Reversible corneal keratopathy was diagnosed in two patients on tamoxifen and eight on high-dose toremifene (P = .061). Treatment had to be discontinued in 17.3% of patients in the high-dose toremifene arm and 20.1% in the tamoxifen arm. Discontinuation due to toxicity was rare, and toxicity did not differ significantly between the treatments. Toremifene, in doses up to 240 mg/d, is an effective, safe treatment for postmenopausal women with ER-positive/unknown advanced breast cancer.