Lomustine

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Lomustine
Names
Trade namesCeeNU, Gleostine, CCNU, others
Other names1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea
  • 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]
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)
  • O=C(NC1CCCCC1)N(N=O)CCCl
  • 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

a-e)Structure and major mode of action of nitrosourea lomustine[5]

It is closely related to semustine and is in the same family as streptozotocin. It is a highly lipid-soluble drug,[6] 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.[7] As with other nitrosoureas, it may also inhibit several key enzymatic processes by carbamoylation of amino acids in proteins.[8] 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."[9][10][11]

Other animals

It has also been used in veterinary practice as a treatment for mast cell tumors in dogs.[12]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 "Lomustine Monograph for Professionals". Drugs.com. Archived from the original on 17 August 2019. Retrieved 24 November 2021.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 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. ↑ Weller, Michael; Le Rhun, Emilie (July 2020). "How did lomustine become standard of care in recurrent glioblastoma?". Cancer Treatment Reviews. 87: 102029. doi:10.1016/j.ctrv.2020.102029. ISSN 1532-1967. Retrieved 4 January 2024.
  6. ↑ "BC Cancer Agency Cancer Drug Manual. Lomustine (CCNU; CeeNU)" (PDF). Archived from the original (PDF) on 17 August 2019. Retrieved 15 July 2016.
  7. ↑ Pizzo PA, Poplack DG, eds. (2006). Principles and Practice of Pediatric Oncology (5th ed.). Philadelphia: Lippincott Williams & Wilkins. p. 300. ISBN 9780781754927.
  8. ↑ "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.
  9. ↑ 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]
  10. ↑ "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.
  11. ↑ "Gleostine (lomustine) Capsules — Healthcare Providers". NextSource Biotechnology. Archived from the original on 23 June 2016. Retrieved 15 July 2016.
  12. ↑ 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.

External links

Identifiers:
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