Droloxifene, a new antiestrogen, in advanced breast cancer. A double-blind dose-finding study. The Droloxifene 002 International Study Group.

To determine the optimal daily dose of the new antiestrogen droloxifene for the treatment of breast cancer, a multinational, multicenter, randomized, double-blind, phase II trial was initiated. Postmenopausal women with progressive advanced breast cancer (distant metastatic cancer, inoperable recurrent or primary tumor) with positive or unknown hormone receptor status (estrogen or progesterone) were entered in the study. Droloxifene was administered in a double-blind randomized design with daily doses of either 20, 40, or 100 mg once daily as first-line systemic therapy. None of the patients had received previous systemic antitumor therapy with the exception of adjuvant chemotherapy terminated at least one year before the patient's recruitment. Response was determined according to Union Internationale Contre le Cancer/World Health Organization criteria. Only patients with at least one measurable lesion were entered into the trial. The highest quality of data was achieved in two ways: source verification in the hospitals through monitors and peer review with subgroups of investigators determining the tumor response of each patient at adjudication meetings (evaluating parameters obtained from physical examination and reviewing X-rays and computer tomography scans). To date, 254 patients have been enrolled. Results from all these groups, without breaking the randomization code, based on 131 patients whose data have been verified are as follows: 10 complete responses (CR), 37 partial responses (PR), 47 no change, 29 progressive disease, 8 patients too early to evaluate. Thus, the overall response rate (CR + PR) was 38%. Droloxifene was well tolerated.