A dose-response relationship has long been suspected for
progestin compounds in the treatment of
breast cancer, but only recently have trials been implemented to investigate this issue. In 1985, we began a phase I-II study of high-dose
megestrol acetate in dosages of 480 mg/d to 1,600 mg/d in heavily pretreated postmenopausal patients with advanced
breast cancer. After establishing the safety of this
therapy, we expanded our trial, which now includes 47 patients, 34 of whom have measurable disease. Of these 34 patients, 30 had
disease progression on prior hormonal
therapy and 29 had progression on
chemotherapy. Six of the 34 patients had complete response and six had partial response for a median time on study of 10 months (range, 8 to 30 months). Ten patients had stabilization and 12 had progression. Thirteen patients had evaluable but nonmeasurable disease, and of these, ten had improvement or stabilization for a median period of 6 months (range, 2 to 18 months) and three had progression. Of 17 patients who had experienced
disease progression while receiving standard-dose
megestrol acetate, 13 (76%) achieved objective remissions or stabilization with high-dose
therapy. The main side effects were
weight gain and appetite enhancement, which were beneficial in 13 underweight patients. These data indicate that high-dose
megestrol acetate is well tolerated and effective in patients with advanced
breast cancer refractory to multiple previous
therapies. While optimal dose levels for clinical use remain to be established by ongoing studies, our data suggest that doses higher than the standard dose may be more effective.