Thiotepa

Thiotepa (INN[3]), sold under the brand name Tepadina, is a medication used to treat cancer.[1][2][4]

Thiotepa
Clinical data
Trade namesTepadina
AHFS/Drugs.comMonograph
MedlinePlusa682821
License data
Pregnancy
category
  • AU: D
Routes of
administration		Intravenous, intracavitary, intravesical
ATC code
Legal status
Legal status
Pharmacokinetic data
MetabolismLiver (CYP2B6, CYP3A)
Elimination half-life1.5–4.1 hours
ExcretionKidney
6 hours for thiotepa
8 hours for TEPA
Identifiers
IUPAC name
  • 1,1′,1′′-Phosphorothioyltriaziridine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.000.124
Chemical and physical data
FormulaC6H12N3PS
Molar mass189.22 g·mol−1
3D model (JSmol)
SMILES
  • S=P(N1CC1)(N2CC2)N3CC3
InChI
  • InChI=1S/C6H12N3PS/c11-10(7-1-2-7,8-3-4-8)9-5-6-9/h1-6H2 Y
  • Key:FOCVUCIESVLUNU-UHFFFAOYSA-N Y
 NY (what is this?)  (verify)

Thiotepa is an organophosphorus compound with the formula (C2H4N)3PS.[5] It is an analog of N,N′,N′′-triethylenephosphoramide (TEPA), which contains tetrahedral phosphorus and is structurally akin to phosphate. It is manufactured by heating aziridine with thiophosphoryl chloride.

Medical uses

Thiotepa is indicated for use in combination with other chemotherapy agents to treat cancer.[1][2][4] This can be with or without total body irradiation (TBI), as a conditioning treatment prior to allogeneic or autologous hematopoietic progenitor cell transplantation (HPCT) in hematological diseases in adults and children.[2][4] These diseases include Hodgkin's disease and leukaemia.[4] Thiotepa is also used with high-dose chemotherapy with HPCT support to treat certain solid tumors in adult and children.[2][4]

Thiotepa is used in the palliation of many neoplastic diseases. The best results are found in the treatment of adenocarcinoma of the breast, adenocarcinoma of the ovary, papillary thyroid cancer and bladder cancer. Thiotepa is used to control intracavitary effusions caused by serosal neoplastic deposits.[4]

Intravesical use

Thiotepa is used as intravesical chemotherapy in bladder cancer.[6]

It may be used prophylactically to prevent seeding of tumor cells at cystoscopic biopsy; as an adjunctive agent at the time of biopsy; or as a therapeutic agent to prevent recurrence after cystoscopic resection of bladder tumor (transurethral resection of bladder tumor, TURBT). Efficacy in tumor control may reach 55%. The main toxicity of this therapy is bone marrow suppression due to systemic absorption of the drug.

Side effects

The main side effect of thiotepa is bone marrow suppression resulting in leukopenia, thrombocytopenia and anemia.[7] Liver and lung toxicity may also occur.

History

Thiotepa was developed by the American Cyanamid company in the early 1950s and reported to media outlets in 1953.[8] In 1959, thiotepa was registered with the Food and Drug Administration (FDA) as a drug therapy for several solid cancers.[9]

On January 29, 2007, the European Medicines Agency (EMA) designated thiotepa as an orphan drug. On April 2, 2007, the United States FDA designated thiotepa as a conditioning treatment for use prior to hematopoietic stem cell transplantation.[10] Adienne Pharma & Biotech (Italy), the owner of thiotepa (Tepadina) applied for these designations.

References
  1. "Tepadina- thiotepa injection, powder, for solution". DailyMed. Retrieved 11 August 2021.
  2. "Tepadina EPAR". European Medicines Agency (EMA). Retrieved 30 April 2021.
  3. "International Non-Proprietary Names for Pharmaceutical Preparations. Recommended International Non-Proprietary Names (Rec. I.N.N.): List 4" (PDF). World Health Organization. March 1962. p. 111. Retrieved 27 November 2016.
  4. "Urgent, Thiotepa update" (PDF). U.S. Food and Drug Administration (FDA). 5 April 2011. Retrieved 25 November 2011.
  5. Maanen MJ, Smeets CJ, Beijnen JH (August 2000). "Chemistry, pharmacology and pharmacokinetics of N,N',N" -triethylenethiophosphoramide (ThioTEPA)". Cancer Treatment Reviews. 26 (4): 257–68. doi:10.1053/ctrv.2000.0170. PMID 10913381.
  6. Droller M (2004). Urothelial Tumors. PMPH-USA. p. 207. ISBN 978-1-55009-173-1.
  7. Agnelli G, de Cunto M, Gresele P, del Favero A (June 1982). "Early onset life-threatening myelosuppression after low dose of intravesical thiotepa". Postgraduate Medical Journal. 58 (680): 380–1. doi:10.1136/pgmj.58.680.380. PMC 2426344. PMID 6812036.
  8. Sykes MP, Karnofsky DA, Philips FS, Burchenal JH (1953). "Clinical studies on triethylenephosphoramide and diethylenephosphoramide, compounds with nitrogen-mustard-like activity". Cancer. 6 (1): 142–148. doi:10.1002/1097-0142(195301)6:1<142::AID-CNCR2820060114>3.0.CO;2-W.
  9. Kim K, Roh JK, Wee H, Kim C (2016). Cancer Drug Discovery: Science and History. Springer. p. 82. ISBN 978-94-024-0844-7.
  10. "EMA Grants Adienne Marketing Rights for Tepadina". dddmag.com. Drug Discovery & Development. 19 March 2010. Retrieved 25 November 2011.
  • "Thiotepa". Drug Information Portal. U.S. National Library of Medicine.
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