Estramustine Other names: Estramustine phosphate ΕΜΡ

Estramustine has a dual mode of action. The intact molecule acts as an anti-miotic agent; after hydrolysis of the carbamate ester, the metabolites act to bridge the released oestrogens and exert an anti-gonadotrophic effect.

Estramustine is a chemical compound of oestradiol and nitrogen mustard. It is effective in the treatment of advanced prostatic carcinoma.

The low level of clinical side effects may be due to the fact that estramustine binds to a protein present in the tumour tissue, so resulting in accumulation of the drug at the target site. Estramustine also has weak oestrogenic and anti-gonadotrophic properties.

Estramustine causes little or no bone marrow depression at usual therapeutic dosage. Estramustine is effective in patients who have not previously received drug therapy, as well as in those who have shown no response to conventional hormone treatment.

Estramustine phosphate sodium is rapidly dephosphorylated in the intestine and prostate to estramustine and estromustine, which accumulate in the prostatic tissue. The plasma half-lives of these metabolites are 10-20 hours. Estramustine and estromustine are further metabolised before excretion.

In repeat dose toxicity studies in rats, dogs and monkeys the main target organs are the hemolymphopoietic and endocrine systems and male and female reproductive organs, with changes related to both oestrogenic and cytotoxic effects of estramustine phosphate.

No reproduction or oncogenicity studies have been undertaken and the mutagenicity of the compound has not fully been investigated. Nevertheless estramustine phosphate, like other oestrogenic and antimitotic agents, must be considered toxic to the reproductive organs and potentially mutagenic and carcinogenic.