Lomustine

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Lomustine
Lomustine.svg
Lomustine ball-and-stick model.png
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
US NLMLomustine
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

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. 1.0 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. "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.

External links

Identifiers: