Lomustine

Lomustine
Names
Trade namesCeeNU, Gleostine, CCNU, others
Other names1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea
IUPAC name
  • N-(2-Chloroethyl)-N'-cyclohexyl-N-nitrosourea
Clinical data
Drug classAlkylating agent[1]
Main usesBrain tumors, melanoma, Hodgkin lymphoma (HL)[1][2]
Side effectsPulmonary fibrosis, low platelets, low white blood cells, low red blood cells, nausea, kidney problems, liver problems[1]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: D
  • US: D (Evidence of risk)
    Routes of
    use    		By mouth (capsules)
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa682207
    Legal
    Legal status
    Pharmacokinetics
    Bioavailability~100%
    Protein binding50%
    MetabolismLiver
    MetabolitesMonoxydroxylated metabolites, trans-4-hydroxy-CCNU, cis-4-hydroxy-CCNU[3]
    Elimination half-life16–48 hours (metabolites)
    Chemical and physical data
    FormulaC9H16ClN3O2
    Molar mass233.70 g·mol−1
    3D model (JSmol)
    Melting point90 °C (194 °F)
    SMILES
    • O=C(NC1CCCCC1)N(N=O)CCCl
    InChI
    • InChI=1S/C9H16ClN3O2/c10-6-7-13(12-15)9(14)11-8-4-2-1-3-5-8/h8H,1-7H2,(H,11,14) checkY
    • Key:GQYIWUVLTXOXAJ-UHFFFAOYSA-N checkY

    Lomustine sold under the brand name CeeNU, is a medication used to treat brain tumors, melanoma, and Hodgkin lymphoma (HL).[1][2] In HL it is used when other treatments have not worked.[1] It is taken by mouth.[1]

    Common side effects include pulmonary fibrosis, low platelets, low white blood cells, low red blood cells, nausea, kidney problems, and liver problems.[1] Other side effects may include hair loss, confusion, vision loss, and mouth inflammation.[2] It should not be used in pregnancy or breastfeeding.[2] It is an alkylating nitrosourea compound.[1]

    Lomustine was approved for medical use in the United States in 1976.[1] It is available as a generic medication.[2] In the United States it costs about 1,050 USD per 100 mg pill as of 2021.[4] This amount in the United Kingdom costs the NHS about £50.[2]

    Medical uses

    Dosage

    By itself it is used at a dose of around 120 to 130 mg/m2 every 6 to 8 weeks.[2]

    Mechanism of action

    It is closely related to semustine and is in the same family as streptozotocin. It is a highly lipid-soluble drug,[5] thus it crosses the blood-brain barrier. Lomustine has a long time to nadir (the time when white blood cells reach their lowest number). It is a monofunctional alkylating agent, alkylates both DNA and RNA, has the ability to cross-link DNA.[6] As with other nitrosoureas, it may also inhibit several key enzymatic processes by carbamoylation of amino acids in proteins.[7] Lomustine is cell-cycle nonspecific.

    Society and culture

    Price

    In the U.S., the patent for lomustine has expired, but only one company manufactures it. In 2013, Bristol-Myers Squibb Co. sold its CeeNU brand of lomustine to CordenPharma, a subsidiary of International Chemical Investors S.E., which markets it as Gleostine through NextSource Biotechnology. In 2013, BMS charged $50 a capsule. In 2018, NextSource charged $768 a capsule. Some doctors said the price increase made it unaffordable, and one doctor called it "price gouging."[8][9][10]

    Other animals

    It has also been used in veterinary practice as a treatment for mast cell tumors in dogs.[11]

    References

    1. 1 2 3 4 5 6 7 8 9 "Lomustine Monograph for Professionals". Drugs.com. Archived from the original on 17 August 2019. Retrieved 24 November 2021.
    2. 1 2 3 4 5 6 7 BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 941. ISBN 978-0857114105.
    3. ↑ Lee FY, Workman P, Roberts JT, Bleehen NM (1985). "Clinical pharmacokinetics of oral CCNU (lomustine)". Cancer Chemotherapy and Pharmacology. 14 (2): 125–31. doi:10.1007/bf00434350. PMID 3971475. S2CID 29619378.
    4. ↑ "Gleostine Prices, Coupons & Patient Assistance Programs". Drugs.com. Retrieved 24 November 2021.
    5. ↑ "BC Cancer Agency Cancer Drug Manual. Lomustine (CCNU; CeeNU)" (PDF). Archived from the original (PDF) on 17 August 2019. Retrieved 15 July 2016.
    6. ↑ Pizzo PA, Poplack DG, eds. (2006). Principles and Practice of Pediatric Oncology (5th ed.). Philadelphia: Lippincott Williams & Wilkins. p. 300. ISBN 9780781754927.
    7. ↑ "Gleostine (lomustine) Capsules, for Oral Use. Full Prescribing Information" (PDF). NextSource Biotechnology, LLC. Archived from the original (PDF) on 16 August 2016. Retrieved 15 July 2016.
    8. ↑ Cancer Drug Price Rises 1400% With No Generic to Challenge It Archived 2018-07-31 at the Wayback Machine, Peter Loftus, The Wall Street Journal, 12/26/2017 [FREE]
    9. ↑ "NextSource Biotechnology Gains FDA Approval for Use of Tradename Gleostine (lomustine), an Anti-Cancer Chemotherapy Agent". www.prnewswire.com. NextSource Biotechnology. Archived from the original on 19 August 2016. Retrieved 15 July 2016.
    10. ↑ "Gleostine (lomustine) Capsules — Healthcare Providers". NextSource Biotechnology. Archived from the original on 23 June 2016. Retrieved 15 July 2016.
    11. ↑ Weiss DJ, Wardrop KJ, Weiss D (2010). Schalm's Veterinary Hematology (6 ed.). John Wiley & Sons, Incorporate d. p. 487. ISBN 978-0-8138-0896-3.
    Identifiers:
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