Phase II, Randomized, Double-Blind Study of Two Dose Levels of Arzoxifene in Patients With Locally Advanced or Metastatic Breast Cancer

Purpose: To select a daily dose of arzoxifene ( LY353381 ), a selective estrogen receptor modulator, for use in future studies in women with locally advanced or metastatic breast cancer who are either potentially tamoxifen sensitive (TS) or tamoxifen refractory (TR). Patients and Methods: This trial was a randomized, double-blind, phase II study of arzoxifene 20 mg (n = 55) and 50 mg (n = 57) in women with advanced or metastatic breast cancer. Patients were randomly assigned to balance for number of metastatic disease sites, prior tamoxifen therapy, and estrogen receptor status. The primary end point was tumor response rate (RR). Secondary end points included clinical benefit rate (CBR), time to progression (TTP), and toxicity. Results: Forty-nine patients were TS and 63 were TR. According to independent review, among TS patients, RR was higher in the 20-mg arm than the 50-mg arm (26.1% v 8.0%), with a longer TTP (8.3 v 3.2 months; P > .05). Among the TR patients, response rate was the same in the 20-mg and 50-mg arms (10.3%) with similar TTP (2.7 and 2.8 months, respectively; P > .05). CBR was higher in the 20-mg arm than in the 50-mg arm among TS patients (39.1% v 20.0%) and TR patients (13.8% v 10.3%). Arzoxifene was well tolerated. Dose-dependent toxicity was not demonstrated. There were no deaths during study. Conclusion: Arzoxifene is effective in the treatment of TS and TR patients with advanced or metastatic breast cancer at the 20-mg and 50-mg dose levels. Toxicities are minimal, and the therapy is tolerated. The 20-mg dose seems to be at least as effective as the 50-mg dose. Accordingly, arzoxifene 20 mg/d was selected for further study in patients with breast cancer.