Phase III studies of toremifene in metastatic breast cancer.

Toremifene has proven to be an effective and well tolerated antiestrogenic compound in the treatment of locally advanced and metastatic breast cancer. Results of phase II studies reveal that the efficacy using a 60 mg daily dose is comparable to tamoxifen. Since toremifene is less toxic in high doses than tamoxifen, in many clinical studies greater than or equal to 200 mg daily doses are used. For more accurate comparison of toremifene and tamoxifen five different clinical phase III studies have been initiated. By December 1, 1989, there were altogether 650 patients accrued into these studies. Two of the studies are double blind comparison of the drugs, one conducted in Finland, Sweden, and Norway, and the other in Denmark. Three open studies are going on, one in the Soviet Union, one in West Germany (BRD), and the third in the USA and Canada. To clarify dose-dependency of toremifene action, a daily dose from 60 mg up to 240 mg is used in these studies compared to 20-40 mg daily doses of tamoxifen. The results of these studies are still too early for critical evaluation, since in the double blind studies no interim comparison of the drugs is possible, and the results of the BRD and USA-Canada open studies will not be analyzed before sufficient patients for statistical evaluation have been included. Preliminary results of the Soviet trial comparing 60 and 240 mg toremifene doses with 40 mg of tamoxifen show that the response rate is highest in the 240 mg toremifene arm, although there are no statistically significant differences. Statistical significance in clinical studies like these is an important aspect of reliability, which based on trial protocols will be critically evaluated and discussed.