|Trade names||Emcyt, Estracyt|
|Synonyms||Leo 299; NSC-89199; Ro 21-8837/001; Estradiol 3-[bis(2-chloroethyl)carbamate] dihydrogen phosphate|
|Drug class||Nitrogen mustard; Alkylating antineoplastic agent; Estrogen; Estrogen ester|
|Metabolites||Estramustine, estromustine, normustine, estradiol, estrone, phosphoric acid|
|Biological half-life||15–24 hours|
|Chemical and physical data|
|Molar mass||520.384 g/mol|
|3D model (JSmol)|
Estramustine phosphate, sold under the brand names Emcyt and Estracyt, is a dual alkylating antineoplastic agent (i.e., a chemotherapy drug) of the nitrogen mustard type and hormonal antineoplastic agent of the estrogen type that is used in the treatment of prostate cancer.
Estramustine phosphate is indicated, in the United States, for the palliative treatment of metastatic and/or progressive prostate cancer, whereas in the United Kingdom it is indicated for the treatment of unresponsive or relapsing prostate cancer.
Estramustine phosphate is contraindicated when used in children, patients hypersensitive to estrogens or nitrogen mustards, those with peptic ulcer (an ulcer in the digestive tract), those with severely compromised liver function, those with weak heart muscle (also known as myocardial insufficiency) and those with thromboembolic disorders or complications related to fluid retention.
Common (1-10% frequency):
- Blood clots and complications thereof (including stroke, heart attack, pulmonary embolism, and thrombophlebitis)
Rare (<0.1% frequency):
Unlike other nitrogen mustards, estramustine phosphate seldom produces significant gastrointestinal or hematologic toxicity such as myelosuppression, the major drug toxicity-related cause of drug discontinuation is thromboembolism (blood clots).
Estramustine phosphate have been reported to increase the toxicity and effectiveness of tricyclic antidepressants like amitriptyline and imipramine. Dairy products like milk and other products containing calcium, aluminium, and magnesium like supplements have been reported to reduce the absorption of estramustine phosphate from the gastrointestinal tract hence reducing oral bioavailability. There may be an increased risk of angioedema in those concurrently taking ACE inhibitors.
Estramustine phosphate acts by two mechanisms: 1) direct cytotoxic activity via inhibition of microtubules (caused by its alkylating nitrogen mustard moiety); and 2) antigonadotropic effects which suppress gonadal androgen production (caused by its estrogenic activity). In regards to the latter, there is depolymerization of the microtubules (which estramustine phosphate achieves by binding to microtubule-associated proteins); this arrests prostate cancer cells in the G2/M phase of the cell cycle. The drug is tissue-selectively taken up by prostate cells and hence produces minimal cytotoxic effects in healthy tissue.
Estramustine phosphate is a prodrug and is delivered as an oral capsule. It is readily taken up from the gastrointestinal tract and then rapidly dephosphorylated into estramustine. Estramustine is then partially oxidized to estromustine. Some estramustine and estromustine undergoes hydrolysis at the ester bond in the liver to form the active metabolites normustine, estradiol, and estrone.
Estramustine phosphate is an estrane steroid and an estrogen ester. It is a derivative and diester of estradiol with a nitrogen mustard-carbamate ester moiety and a phosphate ester attached. Estramustine phosphate is provided as the sodium or meglumine salt. Related although never-marketed drugs include alestramustine, atrimustine, cytestrol acetate, estradiol mustard, ICI-85966, and phenestrol.
Society and culture
Estramustine phosphate is provided as the sodium salt estramustine phosphate sodium (USAN) or estramustine sodium phosphate (BANM, JAN) or as the meglumine salt estramustine phosphate meglumine, and these are the generic names of the drug.
Estramustine phosphate is marketed in the United States, Canada, and Mexico under the brand name Emcyt, whereas the drug is marketed under the brand name Estracyt in the United Kingdom and elsewhere throughout Europe as well as in Argentina, Chile, and Hong Kong. It has been discontinued in a number of markets, including Australia, Brazil, Ireland, and Norway.
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