Lack of correlations between plasma concentration of medroxyprogesterone acetate, hypothalamic-pituitary function, and tumour response in patients with advanced breast cancer.

Plasma medroxyprogesterone acetate (MPA) concentrations were measured in 61 patients with advanced breast cancer, after 3 weeks' treatment using 200 mg PO 8-hourly, to determine whether the previously reported wide interpatient variations correlated with tumour response or toxicity. Seventeen patients (28%) responded to the drug, and their mean plasma MPA concentration was 97 ng/ml +/- 68 SD, compared with 115 ng/ml +/- 87 SD for the patients whose disease progressed. Side-effects attributed to MPA were seen in 18 patients, who had a mean drug concentration of 113 ng/ml +/- 104 SD. This was not significantly higher than that of the patients who did not experience drug toxicity. Because of a suggestion that some of the antitumour activity of the drug could be mediated via an effect on the hypothalamic-pituitary axis, we also measured plasma FSH, LH, and prolactin concentrations after the 3-week treatment with MPA, but found no correlations with either drug concentration or tumour response. These results indicate that with the present treatment schedule the monitoring of plasma MPA concentrations has no role in routine practice and suggest that the inherent sensitivity of the tumour to progesterone is probably the major determinant of response.