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Nitrogen mustards and oxazaphosphorinesUsed in a few countriesSyntheticNeeds review

Estramustine phosphate

Also known as Emcyt, Estramustine phosphate sodium

An oral molecule linking estradiol to a nitrogen mustard by a carbamate bond. FDA-approved in 1981 for metastatic or progressive prostate carcinoma; the US product is listed as discontinued, but 2011 and 2013 reports describe continued clinical use.

From discovery to approval

  1. c. 1975 · Earliest report found

    The earliest paper found is a 1975 report of oral estramustine phosphate (NSC-89199) in 32 patients with stage D prostate carcinoma. No source dates the compound's synthesis or names who made it, so the year shown is only that of this earliest clinical report.[2][1][3]

  2. 1981-12-24 · FDA regular · 6 years after first description

    Emcyt capsules, NDA 018045, original approval, classed as a new molecular entity with standard review in the Drugs@FDA history, which lists the product as discontinued. The original label is not available there; a 2008 label lists palliative treatment of metastatic or progressive carcinoma of the prostate. The type regular is an inference: no accelerated-approval wording was found.[4]

How it works

The US label describes estradiol and nornitrogen mustard joined by a carbamate link, dephosphorylated on absorption, and says prolonged treatment raises plasma estradiol to levels like conventional estradiol therapy. A 2008 cell study suggests effects on microtubules and says the antiproliferative mechanism is not clear.[1]

Where it came from and why

A 2011 review calls it a nitrogen mustard derivative of estradiol-17-beta-phosphate; no source states why it was made.

Cancers

  • Prostate carcinoma

    The 2008 US label lists palliative treatment of metastatic or progressive carcinoma of the prostate; a 1975 report in stage D disease is the earliest paper found.[1]

Worth knowing

  • In the 1975 report of 32 patients with stage D prostate carcinoma, objective remission occurred in seven (22 percent); no haematological, hepatic or renal toxicity was observed, as the authors report.[2]
  • The label warns of an increased risk of thrombosis, including fatal and nonfatal myocardial infarction, in men receiving estrogens for prostatic cancer.[1]
  • Drugs@FDA lists Emcyt as discontinued.[4]
  • In a 2013 retrospective chart review from a Tokyo hospital, 102 patients with castration-resistant prostate cancer received oral estramustine phosphate as third-line therapy; serum PSA fell by more than 50% in 30 (29.4%), as the authors report.[5]
  • A 2011 review says interest in estramustine was renewed by studies showing improved outcomes when it is combined with docetaxel, and that its use can be associated with an increased risk of thromboembolic events.[3]

References

  1. U.S. Food and Drug Administration. Emcyt (estramustine phosphate sodium) capsules, prescribing information, NDA 018045 supplement 023 (action date 9 July 2008; text marked revised June 2007). Source
  2. Mittelman A, Shukla SK, Welvaart K, Murphy GP. Oral estramustine phosphate (NSC-89199) in the treatment of advanced (stage D) carcinoma of the prostate. Cancer Chemother Rep. 1975;59(1):219-23. PubMed
  3. Ravery V, Fizazi K, Oudard S, Drouet L, Eymard JC, Culine S, et al. The use of estramustine phosphate in the modern management of advanced prostate cancer. BJU Int. 2011;108(11):1782-6. PubMedDOI
  4. U.S. Food and Drug Administration. Drugs@FDA: Approval date(s) and history, letters, labels, reviews for NDA 018045 (Emcyt, estramustine phosphate sodium). Page read 2026-10-26. Source
  5. Matsumoto K, Tanaka N, Hayakawa N, Ezaki T, Suzuki K, Maeda T, et al. Efficacy of estramustine phosphate sodium hydrate (EMP) monotherapy in castration-resistant prostate cancer patients: report of 102 cases and review of literature. Med Oncol. 2013;30(4):717. PubMedDOI
  6. Mohan R, Panda D. Kinetic stabilization of microtubule dynamics by estramustine is associated with tubulin acetylation, spindle abnormalities, and mitotic arrest. Cancer Res. 2008;68(15):6181-9. PubMedDOI