PHASE-I TRIAL OF DROLOXIFENE IN PATIENTS WITH METASTATIC BREAST-CANCER

Droloxifene (3-hydroxytamoxifen) is a new, nonsteroidal antiestrogen. In comparison with tamoxifen, it has a 10- to 64-fold higher affinity for the estrogen receptor and has shown a lower estrogenic and higher antiestrogenic effect in experimental studies. The objective of this s tudy was to determine the toxicity (and its reversibility) of droloxif ene given at different doses to patients with advanced metastatic brea st cancer refractory to conventional endocrine therapy and chemotherap y. In this study, 30 patients were treated in groups of 6 at 5 differe nt doses (20, 40, 100, 200, and 300 mg) by mouth once a day. Toxic eff ects included hot flashes, nausea, and fatigue and were not dose-relat ed. Toxicity did not require any dose reduction or discontinuation of therapy. There was one episode of deep venous thrombosis and pulmonary embolism. There was no complete or partial response in this study, bu t four patients showed a minor response (13%). These data illustrate t hat this drug is well tolerated and needs to be further evaluated in p hase II and III studies.