Background: More efficacious and safer hormonal agents are needed for breast cancer treatment and prevention. Idoxifene is a novel selective estrogen receptor modulator (SERM) that, in preclinical models, has greater antiestrogenic but lower estrogenic activity than tamoxifen.
Patients and methods: Three hundred and twenty-one postmenopausal patients with hormone receptor-positive or -unknown metastatic breast cancer were randomized to receive either tamoxifen or idoxifene as initial endocrine therapy for advanced disease. Data were analyzed based on intention to treat and all the responses were subject to independent review.
Results: At the time of a second planned interim analysis, the trial was stopped for economic considerations, not for reasons related to safety or efficacy. Complete data for the 219 patients included in the second interim analysis are fully available and reported here. Median age was 59.1 years for idoxifene patients and 59.9 years for tamoxifen patients. Complete response (CR) plus partial response (PR) rates were as follows: tamoxifen, 9%; idoxifene, 13% (P = 0.39). Clinical benefit rate [CR + PR + stable disease (SD) >or=6 months] was 34.3% for idoxifene and 38.7% for tamoxifen (P = 0.31). Median time to progression and duration of response were 140 days and 151.5 days, respectively, for tamoxifen compared with 166 days and 218 days for idoxifene. None of these endpoints was significantly different for the two drugs, nor was survival. Adverse events (lethal, serious but not lethal and important but not life threatening) were similar in the two arms.
Conclusions: Idoxifene was both active and well tolerated in postmenopausal women with metastatic breast cancer. Idoxifene had similar efficacy and toxicity to tamoxifen in this randomized comparison.