Pharmacoclinical data on high dose medroxyprogesterone acetate in advanced breast cancer.

Abstract

Clinical pharmacokinetic data on medroxyprogesterone acetate (MPA) are conflicting: certain investigations have reported a direct association between drug bioavailability and objective (1) or subjective (2) response to MPA, whereas others (3) arrive at negative conclusions on this same point. In view of this disparity in MPA analytical procedures and their corresponding conclusions, we felt it worthwile to re-evaluate the relationship between circulating MPA levels and treatment efficiency. A total of twenty-eight patients with advanced breast cancer were treated in our institution by MPA monotherapy. Eighteen of these patients had previously received hormone therapy (tamoxifen, 30mg/day per os) and chemotherapy (multidrug regimens including adriamycin), and 6 others had received only hormone therapy. For the remaining 4 patients MPA constituted the first treatment. None of the patients had hepatic or renal failure, and no patient with past or present cardiovascular diseases was entered in the study. All patients were women, and mean age was 67 years (range 45-84). High dose MPA was administered per os (2 x 500mg/day, 8a.m, 8p.m; 22 patients) or im (500mg/day, 8a.m; 6 patients) on an outpatient basis. At these dosages, the two administration forms are bioequivalent (4). Patients were examined at 3 months for evaluation of response and tolerance to treatment according to VICC criteria. They were followed for a mean period of 7 months (range 3-36). Blood samples were obtained each month at 8 a.m just before daily oral intake or im administration of MPA in order to determine the minimum steady state blood concentration which is not influenced by the peak absorption value. MPA was measured in plasma as previously described (5), based on HPLC separation of MPA and UV detection at 250nm. Steroid hormone receptors were assayed by the classical technique using dex