DROLOXIFENE IN POSTMENOPAUSAL PATIENTS WITH METASTATIC BREAST-CANCER - DOUBLE-BLIND RANDOMIZED PHASE-II STUDY

Droloxifene (3-OH-tamoxifen) is a new, highly effective antiestrogen. In preclinical and early clinical trials a strong antineoplastic efficacy was stated, at least as effective as that of tamoxifen. The rationale of the trial was the definition of the optimal daily dose. The trial was double-blind randomized and included in total 369 female breast cancer patients with advanced disease. The interim analysis included 234 fully evaluable patients. The objective remission rates were 31% (20 mg/day), 45% (40 mg/day) and 42% (100 mg/day). There was a trend for higher remission rates in the 40- and 100-mg groups. However, this was not statistically significant (p = 0.0528). The remissions were noticed very early. The medians for subjective response (pain) and objective response (CR/PR) were noted after 2 and 8 weeks, respectively. The median time to progression was 6 months (20 and 100 mg/day) and 8.3 months (40 mg/day). The course of tumor markers demonstrated the rapid onset of the action of droloxifene. Droloxifene was well tolerated in all three dosages. As clinically relevant side effects, hot flushes and nausea were noticed. A clinically irrelevant and transient increase in the gamma GT level was noticed during the first 2 weeks of treatment. The recommended daily dose for phase III trials is 40 mg.