High dose toremifene in advanced breast cancer resistant to or relapsed during tamoxifen treatment.

Fifty patients with advanced breast cancer refractory to prior tamoxifen therapy were assigned to investigational treatment with high-dose toremifene administered 120 mg orally twice a day. Treatment was generally well tolerated. The majority (80%) of the patients had no side effects, and among the remaining 10 patients reported side effects were mostly mild and/or transient. Two objective tumor responses were observed: one complete response (CR), duration 6.2 months, and one partial response (PR), duration 8 months. The response rate was thus 4% (95% CI: 0.5 to 14%). In addition 3 patients experienced a mixed response, some metastatic sites responding, while at other sites disease progressed; 22 patients had disease stabilization for > 2 months. A subset analysis disclosed that a small subgroup of patients, including 7 patients in this study, who had achieved CR at some of the sites during preceding tamoxifen therapy, experienced a long progression-free time during high dose toremifene treatment. The median time to progression in this subgroup of patients was 9.4 months (95% CI: 3.8 to 9.4) as opposed to 2.1 months (95% CI: 2.0 to 2.8) for all the remaining 43 patients, which is a significant decrease in disease progression (p < 0.03). Such results reveal that although this kind of second-line hormonal treatment with high dose toremifene cannot be recommended for all tamoxifen failures, there might be a subset of patients, i.e. those who achieve CR in some lesion during tamoxifen therapy, who benefit from this type of treatment.