Oral high-dose medroxyprogesterone acetate (MAP) in treatment of advanced breast cancer
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Medroxyprogesterone acetate (MAP) in the treatment of advanced breast cancer has been regarded as a minor agent according to the previous reports when used at low doses (<500 mg/day). High doses of more than 500 mg which have come into use since 1973 give a response rate of over 40%, but sometimes cause gluteal abcess or induration because of daily intramuscular injections.
In order to administer easily and to avoid the side effect, we have attempted to use oral administration in a daily dose of 1200mg (400 mg × 3). Of those 20 patients treated with oral high-dose MAP, 1 showed complete response, 6 showed partial response, 7 no change, and 6 progressive disease. As for site of lesion, 4 out of 6 (67%) in skin and 4 out of 16 (25%) in bone responded. Neither severe side effects nor abnormal laboratory data were seen.
Then, we examined the blood levels of MAP in vivo by RIA in 9 patients. The blood level of MAP reached 39–250 ng/ml in 3 days and was maintained at least over 50 ng/ml for 1 or 2 months of continuous administration. Subsequently, we examined the effects of MAP on binding to ER in vitro. The inhibition of binding of estradiol-17β to ER was about 60% at 10−5 M MAP. The blood level of 50 ng/ml in vivo corresponds to about 1.3 × 10−5 M.
Keywordsmedroxyprogesterone acetate (MAP) oral high-dose hormone therapy breast cancer
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