HIGH-DOSE TOREMIFENE FOR ESTROGEN AND PROGESTERONE-RECEPTOR NEGATIVE METASTATIC BREAST-CANCER - A PHASE-II TRIAL OF THE CANCER AND LEUKEMIAGROUP-B (CALGB)

In pre-clinical and limited clinical studies, high doses (greater than or equal to 200 mg/day) of the triphenylethylene derivative toremifen e showed activity in estrogen receptor (ER) negative and ER-unknown me tastatic breast cancer after progression on tamoxifen, and a mechanism of action independent of hormone receptor binding was speculated. The CALGB conducted a Phase II trial (CALGB 8945) to test the efficacy of high dose toremifene in a population of patients who had hormone rece ptor-negative, metastatic breast cancer with limited prior chemotherap y exposure, good performance status, and measurable disease. Twenty el igible patients received toremifene at a dose of 400 mg/day orally for 8 weeks. Toxicity was minimal. Nausea was reported by 20% of the pati ents, lightheadedness by 20%, weight loss by 20%, and hot flashes by 1 5%. There was no grade 3-4 toxicity. No objective responses were obser ved, and 5 of 6 patients with stable disease at 8 weeks developed prog ressive disease at 11 to 33 weeks. High dose toremifene (400 mg/day) i s well-tolerated but imparts no detectable activity in hormone recepto r-negative, metastatic breast cancer.