Estramustine
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| Systematic (IUPAC) name | |
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(17β)-17-Hydroxyestra-1(10),2,4-trien-3-yl bis(2-chloroethyl)carbamate
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| Clinical data | |
| Trade names | Emcyt |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a608046 |
| Licence data | US FDA:link |
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| Pharmacokinetic data | |
| Bioavailability | 75%[1] |
| Metabolism | Hepatic to estradiol and estrone[1] |
| Biological half-life | 15-24 hours[1] |
| Excretion | Faeces (2.9-4.8%)[1] |
| Identifiers | |
| CAS Number | 2998-57-4  |
| ATC code | L01XX11 (WHO) |
| PubChem | CID: 259331 |
| DrugBank | DB01196 |
| ChemSpider | 227635 |
| UNII | 35LT29625A |
| KEGG | D04066 |
| ChEBI | CHEBI:4868 |
| ChEMBL | CHEMBL1575 |
| Chemical data | |
| Formula | C23H31Cl2NO3 |
| Molecular mass | 440.403 g/mol |
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Estramustine (Emcyt, Estracit) is an antimicrotubule chemotherapy agent used to treat prostate cancer. It is a derivative of oestrogen (specifically, estradiol) with a nitrogen mustard-carbamate ester moiety. It has been withdrawn from a number of markets (Australia, Brazil, Ireland and Norway).[2]
Contents
Clinical uses
Estramustine is indicated, in the US, for the palliative treatment of metastatic and/or progressive prostate cancer.[1] Whereas in the UK it is indicated for the treatment of unresponsive or relapsing prostate cancer.[3][4][5][6]
Adverse effects
Adverse effects by frequency:[1][3]
Very common (>10% frequency):
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- Oedema
- Dyspnoea
- Nausea
- Diarrhoea
- Breast tenderness and enlargement
Common (1-10% frequency):
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- Lethargy
- Insomnia
- Congestive heart failure
- Easy bruising
- Anorexia
- Vomiting
- Itchiness
- Dry skin
- Impotence
- Leg cramps
- Decreased testosterone
- Impaired liver function
- Blood clots and complications thereof (including stroke, heart attacks, pulmonary embolism and thrombophlebitis)
Rare (<0.1% frequency):
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- Anaemia
- Leucopenia
- Thrombocytopenia
- Confusion
- Depression
- Headache
- Lethargy
- Muscle weakness
- Angiooedema, occurs most commonly when used in combination with ACE inhibitors.
Unlike other nitrogen mustards it seldom produces significant GI or haematologic toxicity such as myelosuppression,[4] the major drug toxicity-related cause of drug discontinuation is thromboembolism (blood clots).[7]
Contraindications
It is contraindicated when used in children, patients hypersensitive to estradiol 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.[3]
Interactions
Oestrogen mimics like estramustine have been reported to increase the toxicity and therapeutic efficacy of tricyclic antidepressants like amitriptyline and imipramine.[3] Dairy products and other products containing calcium, aluminium and magnesium have been reported to reduce the absorption of estramustine from the gastrointestinal tract hence reducing bioavailability.[3] There may be an increased risk of angiooedema in those concurrently taking ACE inhibitors.[3]
Mechanism of action
Its therapeutic actions are believed to be related to its ability to depolymerising the microtubules (which it achieves by binding to microtubule associated proteins), this arrests prostate cancer cells in the G2/M phase of the cell cycle.[4][5][6] It is selectively taken up by prostate cells and hence produces minimal cytotoxic effects on healthy tissue.[4]
Pharmacokinetics
Estramustine is delivered as an oral capsule. It is readily taken up from the gastrointestinal tract and then rapidly dephosphorylated from estramustine phosphate to estramustine.[4] Estramustine is then partially oxidised to estromustine.[4] Some estramustine and estromustine undergoes hydrolysis at the ester bond in the liver to form estradiol, estrone and normustine.[4] Milk, calcium, aluminium and magnesium supplements may reduce bioavailability.[3]
| Estramustine | Estromustine | Estradiol | Estrone | Normustine |
|---|---|---|---|---|
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See also
References
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