ThioTEPA

Thiotepa
Systematic (IUPAC) name
1,1',1''-phosphorothioyltriaziridine
Clinical data
AHFS/Drugs.com Consumer Drug Information
MedlinePlus a682821
Pregnancy cat. D(AU) D(US)
Legal status POM (UK) ℞-only (US)
Routes IV, intracavitary, intravesical
Pharmacokinetic data
Metabolism Hepatic (CYP2B, CYP3A)
Half-life 1.5-4.1 hours
Excretion Renal
6 hours for ThioTEPA
8 hours for TEPA
Identifiers
CAS number 52-24-4 Y
ATC code L01AC01
PubChem CID 5453
DrugBank DB04572
ChemSpider 5254 Y
UNII 905Z5W3GKH Y
KEGG D00583 Y
ChEMBL CHEMBL671 Y
Chemical data
Formula C6H12N3PS 
Mol. mass 189.23 g/mol
SMILES eMolecules & PubChem
 N(what is this?)  (verify)

N,N'N'-triethylenethiophosphoramide (ThioTEPA or thiotepa) is an alkylating agent used to treat cancer.

ThioTEPA is an organophosphorus compound with the formula SP(NC2H4)3.[1] It is an analogue of N,N',N''- triethylenephosphoramide (TEPA). This molecule features tetrahedral phosphorus and is structurally akin to phosphate. It is derived from aziridine and thiophosphoryl chloride.

History and use

ThioTEPA was first developed by American Cyanamid company in the early 1950s and was reported in 1953.[2] ThioTEPA has been in use since the 1960s.

ThioTEPA has been designated as orphan drug by the European Medicines Agency on January 29, 2007, and by the United States Food and Drug Administration (FDA) on April 2, 2007, as a conditioning treatment prior to haematopoietic stem cell transplantation.[3] The applicant for these orphan drug designations was the italian company ADIENNE Pharma & Biotech, owner of the drug TEPADINA (INN: thiotepa).

Thiotepa is indicated, in combination with other chemotherapy medicinal products:

Thiotepa has been previously used in the palliation of a wide variety of neoplastic diseases. The more consistent results have been seen in: adenocarcinoma of the breast, adenocarcinoma of the ovary, superficial papillary carcinoma of the urinary bladder and for controlling intracavitary effusions secondary to diffuse or localized neoplastic diseases of various serosal cavities.[4]

Thiotepa main toxicity is myelosuppression. The most serious complication of excessive therapy is bone marrow depression, causing leukopenia, thrombocytopenia, and anemia.[5] Serious toxicity involving the hematologic, hepatic and respiratory system were considered as expected consequences of the conditioning regimen and transplant process.

References

  1. ^ Maanen MJ, Smeets CJ, Beijnen JH (2000). "Chemistry, pharmacology and pharmacokinetics of N,N',N" -triethylenethiophosphoramide (ThioTEPA)". Cancer Treat Rev 26 (4): 257–68. doi:10.1053/ctrv.2000.0170. PMID 10913381. 
  2. ^ Sykes M et al. (1953). "The relation between deoxycytidine kinase activity and the radiosensitising effect of gemcitabine in eight different human tumour cell lines". Cancer 6: 142–48. doi:10.1002/1097-0142(195301)6:1<142::AID-CNCR2820060114>3.0.CO;2-W. PMC 1513392. PMID 16734894. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1513392. 
  3. ^ "EMA Grants Adienne Marketing Rights for Tepadina". dddmag.com. Drug Discovery & Development. 19 March 2010. http://www.dddmag.com/news-EMA-Grants-Adienne-Marketing-Rights-for-Tepadina-31910.aspx. Retrieved 25 November 2011. 
  4. ^ a b "URGENT – THIOTEPA UPDATE". Food and Drug Administration. ADIENNE Pharma & Biotech. 5 April 2011. http://www.fda.gov/downloads/Drugs/DrugSafety/DrugShortages/UCM251666.pdf. Retrieved 25 November 2011. 
  5. ^ Early onset life-threatening myelosuppression after low dose of intravesical thiotepa. Agnelli G, de Cunto M, Gresele P, del Favero A Postgrad Med J 1982;58:380-1.

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