Thiotepa

Thiotepa
Names
Trade namesTepadina
IUPAC name
  • 1,1′,1′′-Phosphorothioyltriaziridine
Clinical data
Drug classAlkylating agent[1]
Main usesCancer, pterygium.[2]
Side effectsLow blood cells, graft-versus-host disease, blood in the urine, mucosal inflammation[1]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: D
    Routes of
    use    		Intravenous, intracavitary, intravesical
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa682821
    Legal
    License data
    Legal status
    Pharmacokinetics
    MetabolismLiver (CYP2B, CYP3A)
    Elimination half-life1.5–4.1 hours
    ExcretionKidney
    6 hours for thiotepa
    8 hours for TEPA
    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 checkY
    • Key:FOCVUCIESVLUNU-UHFFFAOYSA-N checkY

    Thiotepa, sold under the brand name Tepadina, is a medication primarily used to treat cancer.[2] This includes bladder, breast, ovarian, and lymphoma.[2] Such use; however, is not recommended by Scotland.[3] Other uses include, as an eye drop, for pterygium.[2]

    Common side effects include low blood cells, graft-versus-host disease, blood in the urine, and mucosal inflammation.[1] Other side effects may include further cancer and anaphylaxis.[2] Use in pregnancy may harm the baby.[3] It is an alkylating agent and works by giving cells that divide rapidly.[1]

    Thiotepa was approved for medical use in the United States in 1959.[2] It was approved in Europe in 2010, though has been used for decades before this.[1] In the United States it costs about 3,600 USD for 100 mg.[4]

    Medical uses

    Thiotepa is used in combination with other chemotherapy agents to treat cancer.[1][5] 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.[1][5] These diseases include Hodgkin's disease and leukaemia.[5] Thiotepa is also used with high-dose chemotherapy with HPCT support to treat certain solid tumors in adult and children.[1][5]

    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.[5]

    Bladder

    Thiotepa is given into the bladder for 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.

    Chemistry

    It is an organophosphorus compound with the formula SP(NC2H4)3.[8] 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.

    History

    Thiotepa was developed by the American Cyanamid company in the early 1950s and reported to media outlets in 1953.[9] In 1959, thiotepa was registered with the Food and Drug Administration (FDA) as a drug therapy for several solid cancers.[10]

    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.[11] Adienne Pharma & Biotech (Italy), the owner of thiotepa (Tepadina) applied for these designations.

    Society and culture

    "Thiotepa" is the INN.[12]

    References

    1. 1 2 3 4 5 6 7 8 9 "Tepadina EPAR". European Medicines Agency (EMA). Archived from the original on 6 March 2021. Retrieved 30 April 2021.
    2. 1 2 3 4 5 6 "Thiotepa Monograph for Professionals". Drugs.com. Archived from the original on 13 August 2020. Retrieved 3 October 2021.
    3. 1 2 BNF (80 ed.). BMJ Group and the Pharmaceutical Press. September 2020 – March 2021. p. 950. ISBN 978-0-85711-369-6.{{cite book}}: CS1 maint: date format (link)
    4. ↑ "Thiotepa Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 24 January 2021. Retrieved 3 October 2021.
    5. 1 2 3 4 5 "Urgent, Thiotepa update" (PDF). U.S. Food and Drug Administration (FDA). 5 April 2011. Archived (PDF) from the original on 9 November 2011. Retrieved 25 November 2011.
    6. ↑ Droller M (2004). Urothelial Tumors. PMPH-USA. p. 207. ISBN 978-1-55009-173-1. Archived from the original on 2021-08-29. Retrieved 2021-07-04.
    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. ↑ 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.
    9. ↑ 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.
    10. ↑ Kim K, Roh JK, Wee H, Kim C (2016). Cancer Drug Discovery: Science and History. Springer. p. 82. ISBN 978-94-024-0844-7.
    11. ↑ "EMA Grants Adienne Marketing Rights for Tepadina". dddmag.com. Drug Discovery & Development. 19 March 2010. Retrieved 25 November 2011.
    12. ↑ "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. Archived (PDF) from the original on 18 May 2016. Retrieved 27 November 2016.
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