Lomustine

Lomustine
Clinical data
Trade names Gleostine
Synonyms 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea
AHFS/Drugs.com Monograph
MedlinePlus a682207
Pregnancy
category
  • AU: D
  • US: D (Evidence of risk)
    Routes of
    administration    		 Oral (capsules)
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Bioavailability ~100%
    Protein binding 50%
    Metabolism Liver
    Metabolites Monoxydroxylated metabolites, trans-4-hydroxy-CCNU, cis-4-hydroxy-CCNU[1]
    Elimination half-life 16–48 hours (metabolites)
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    ECHA InfoCard 100.032.585 Edit this at Wikidata
    Chemical and physical data
    Formula C9H16ClN3O2
    Molar mass 233.695 g/mol
    3D model (JSmol)
    Melting point 90 °C (194 °F)
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    Lomustine (INN), abbreviated as CCNU (original brand name (formerly available) is CeeNU, now marketed as Gleostine), is an alkylating nitrosourea compound used in chemotherapy. It is closely related to semustine and is in the same family as streptozotocin. It is a highly lipid-soluble drug,[2] thus it crosses the blood-brain barrier. This property makes it ideal for treating brain tumors, which is its primary use, although it is also used to treat Hodgkin lymphoma as a second-line option.[3] Lomustine has a long time to nadir (the time when white blood cells reach their lowest number).

    Unlike carmustine, lomustine is administered orally. It is a monofunctional alkylating agent, alkylates both DNA and RNA, has the ability to cross-link DNA.[4] As with other nitrosoureas, it may also inhibit several key enzymatic processes by carbamoylation of amino acids in proteins.[5] Lomustine is cell-cycle nonspecific.

    It has also been used in veterinary practice as a treatment for mast cell tumors in dogs.[6]

    Price increase

    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."[7][8][9]

    References

    1. ↑ 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.
    2. ↑ "BC Cancer Agency Cancer Drug Manual. Lomustine (CCNU; CeeNU)" (PDF). Retrieved 15 July 2016.
    3. ↑ "PRODUCT INFORMATION CeeNU®(lomustine)" (PDF). TGA eBusiness Services. Bristol-Myers Squibb Australia Pty Ltd. 30 September 2015. Retrieved 23 April 2018.
    4. ↑ Pizzo, PA; Poplack, DG, eds. (2006). Principles and Practice of Pediatric Oncology (5th ed.). Philadelphia: Lippincott Williams & Wilkins. p. 300. ISBN 9780781754927.
    5. ↑ "Gleostine (lomustine) Capsules, for Oral Use. Full Prescribing Information" (PDF). NextSource Biotechnology, LLC. Retrieved 15 July 2016.
    6. ↑ Weiss, Douglas J.; Wardrop, K. Jane; Weiss, Douglass (2010). Schalm's Veterinary Hematology (6 ed.). John Wiley & Sons, Incorporated. p. 487. ISBN 978-0-8138-0896-3.
    7. ↑ Cancer Drug Price Rises 1400% With No Generic to Challenge It, Peter Loftus, The Wall Street Journal, 12/26/2017 [FREE]
    8. ↑ "NextSource Biotechnology Gains FDA Approval for Use of Tradename Gleostine (lomustine), an Anti-Cancer Chemotherapy Agent". www.prnewswire.com. NextSource Biotechnology. Retrieved 15 July 2016.
    9. ↑ "Gleostine (lomustine) Capsules — Healthcare Providers". NextSource Biotechnology. Retrieved 15 July 2016.
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