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Antiprogestins, a New Form of Endocrine Therapy for Human Breast Cancer¹

Department of Medical Oncology (Division of Endocrine Oncology) [J. G. M. K., G. H. B., C. J. R., J. A-F.], Dr. Daniel den Hoed Cancer Center, and Department of Endocrinology [F. H. d. J., S. W. J. L.], Erasmus University, Rotterdam, The Netherlands

The antitumor, endocrine, hematological, biochemical, and side effects of chronic second-line treatment with the antiprogestin mifepristone (RU 486) were investigated in 11 postmenopausal patients with metastatic breast cancer. We observed one objective response, 6 instances of short-term stable disease, and 4 instances of progressive disease. Mean plasma concentrations of adrenocorticotropic hormone (P < 0.05), cortisol (P < 0.001), androstenedione (P < 0.01), and estradiol (P < 0.002) increased significantly during treatment accompanied by a slight decrease of sex hormone binding globulin levels, while basal and stimulated gonadotropin levels did not change significantly. The increased basal cortisol levels could not be further stimulated by synacthen, nor suppressed by 1 mg of dexamethasone. Plasma estradiol concentrations were significantly correlated with both androstenedione (P < 0.05) and cortisol levels (P < 0.01). The percentage of eosinophilic white blood cells (P < 0.02) and mean plasma creatinine concentration (P < 0.05) increased significantly. Side effects frequently occurred during long-term treatment and appeared to be caused mainly by the antiglucocorticoid properties of the drug. It is concluded that antiprogestins form a new treatment modality in the endocrine treatment of human breast cancer. New antiprogestins with less antiglucocorticoid side effects might be especially of value as an adjunct to antiestrogenic treatment in view of our finding that combined antiestrogenic and antiprogestational treatment caused additive growth-inhibitory effects in rat mammary tumors.

¹ This study was supported by The Netherlands Cancer Foundation (KWF-CKVO 86-09) and Roussel B. V. (Hoevelaken).

² To whom requests for reprints should be addressed, at Division of Endocrine Oncology (Biochemistry and Endocrinology), Dr. Daniel den Hoed Cancer Center, P. O. Box 5201, 3008 AE Rotterdam, The Netherlands.

Received 10/31/88. Revised 1/30/89. Accepted 3/ 1/89.

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