Tamoxifen Medroxyprogesterone

For those who do not respond to tamoxifen, second-line therapy includes progestogens, e.g. megestrol or medroxyprogesterone. Should fluid reten-... 

Progestins such as megestrol acetate and medroxyprogesterone acetate have been compared with tamoxifen in randomized trials and have been found to yield equal response rates. Although there were no direct comparisons of these two forms of progestational therapy, they appear to be equally effective. Medroxyprogesterone acetate is... 

Noguchi, S., Yamamoto, H., Inaji, H., Imaoka, S., and Koyama, H., Influence of tamoxifen-medroxyprogesterone sequential therapy on estrogen and progesterone receptor contents of breast cancer. Jpn. J. Cancer Res. 80(3), 244-248 (1989). 

Fig. 14.8. Chemical diagrams a diethylstilbestrol b f-pseudo-diethylstilbestrol, EPD c Z-pseudo-diethylstilbestrol, ZPD d /rows-tamoxifen e medroxyprogesterone acetate f 17a,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione (R5020) g 1 lyS-(4-(dimethyl-amino)phenyl)-l7J8-hy-droxy-17a-(l-propynyl)estra-4,9-dien-3-one (RU38486) h flutamide i l7j8-hydroxy-17a-methyl-4,9,1 l-estratrien-3-one...

Medroxyprogesterone affects the metabolism of tamoxifen but the clinical importance of this is uncertain. 

In 20 women with breast eaneer taking tamoxifen 20 mg twice daily, the addition of medroxyprogesterone acetate 500 mg twice daily only slightly reduced the tamoxifen serum levels over a 6-month period, but considerably reduced the levels of the desmethyl metabolite of tamoxifen, presumably because of some effect on the metabolism of the tamoxifen by the liver. The clinical importance of this interaction awaits assessment. 

Reid AD, Horobin JM, Newman EL, Preece PE. Tamoxifen metabolism is altered simultaneous administraticn of medroxyprogesterone acetate in breast cancer patients. Breast Cancer Res Treat 992) 22,153-6... 

Tamoxifen induced signs of autophagy in the FM3 murine breast tumour cell line, which was enhanced when it was combined with medroxyprogesterone (Bilir et al. 2001). 

The newer anthracyclines, both epirabicin and idarabicin, profoundly inhibited human polymorphonuclear superoxide generation (P < 0.02 and (P < 0.01), respectively (Cairo et al. 1990). Epirubicin treatment of FM3A murine breast tumour cells resulted in autophagocytosis of secretory granules (Bilir et al. 2001). Combining medroxyprogesterone with epirubicin enhanced the formation of apoptotic blebs and chromatin fragmentation. When epirubicin was combined with tamoxifen, peculiar nuclear structures were formed. 

Bilir, A., Altinoz, M.A., Erkan, M., Ozmen, V., and Aydiner, A. (2001). Autophagy and nuclear changes in FM3A breast tumor cells after epirubicin, medroxyprogesterone and tamoxifen treatment in vitro. Pathobiology 69, 120-126. 

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