Treatment of carcinoma of the breast with high dose oral medroxyprogesterone acetate: does increased bioavailability improve the therapeutic ratio?

Medroxyprogesterone acetate (MPA) is regarded as a valuable hormonal therapy for metastatic breast cancer. The drug is manufactured by more than one pharmaceutical company, and one particular brand of oral MPA (Provera Tablets, Upjohn) has been reformulated to incorporate micronized particles, providing significantly enhanced bioavailability. The response rate and side-effect data from a pilot study, which used the old formulation Provera Tablets 100 mg at a dosage of 800 mg/day in 28 patients with recurrent breast cancer after treatment with tamoxifen, are compared with those from another study in which 59 similar patients received 800 mg/day of new formulation Provera Tablets 200 mg. Neither of these studies, conducted in the United Kingdom, has previously been published. The response rates were similar in both studies, but there were higher incidences of significant weight gain and increased blood pressure in those patients treated with the new formulation. These side effects have been noticed by other workers employing new formulation MPA at a dosage of 800 mg per day, while it has been reported that reducing the dosage to 400 mg perday is accompanied by a lower incidence of side effects, without affecting the response rate. It is concluded that the increased serum levels of MPA, made possible by the micronized product, do not favourably influence the response of metastatic breast cancer to therapy, but may be associated with a higher incidence of side effects. Reducing the dosage of the new formulation MPA to 400 mg/day may allow a more acceptable side-effect profile, without loss of therapeutic efficacy. Such a dose reduction would make this brand of MPA more cost effective.