A prospective randomized trial to evaluate different oral dose regimens of medroxyprogesterone acetate in women with advanced breast cancer

A prospective randomized study was conducted to try to answer two questions: is a loading dose of medroxyprogesterone acetate (1000 mg p.o. q.d.s. for 48 h) superior to conventional dosing; and does an oral maintenance dose of 1000 mg daily offer any advantage over 500 mg daily in women with advanced breast cancer who have failed to respond to, or have relapsed after, tamoxifen? Of 211 patients randomized, 207 were evaluable. There was no improvement in response rates, time to response, response duration or overall survival as a result of the loading dose. When comparing high and low maintenance doses, there was a significant difference in response rates (48% versus 32%; x2 = 10.09, df = 2, P = 0.006) and survival (66% versus 41% alive at 12 months; x2= 9.06, df = 1, P = 0.003) in favour of the higher dose regimen, although there was no significant difference in the duration of response. There was no additional toxicity attributable to the loading dose regimen, but side effects were more frequent with the high dose maintenance schedule (141 of 201 adverse effects occurring in these two groups) although the incidence of severe toxicity was similar with both high dose and low dose treatments.