Lomustin

Last updated on: 29.10.2020

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Synonym(s)

CAS number:154-93-8; CCNU; Chlorethyl-Cyclohexyl-Nitroso-Urea

Definition
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Lomustine, also known as CCNU, is a cytostatic drug (molecular formula C9H16ClN3O2) from the group of nitrosoureas, which is used in the treatment of certain severe, advanced cancers. Lomustine, like the nitrogen-lost derivatives and the related nitrosourea carmustine, contains chloroethyl residues and additionally a highly reactive nitroso group. The substances decompose spontaneously and release the alkylating ethyl carbonium ion, which causes cross-linking of the DNA by alkylation of guanine and cytosine. In addition, isocyanates are formed, which also inhibit DNA repair by combining with the DNA polymerase. Lomustin and carmustin have a non-phase-specific effect, i.e. they also act on resting cells.

Undesirable effects
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Bone marrow damage, a reduced platelet and leukocyte count, nausea and hair loss are common.

Lomustine can also cause liver and kidney damage

With nitrosourea these side effects occur with a delay. For this reason, constant monitoring of blood values and treatment breaks of about 6 weeks are necessary.

Toxic lung changes: Rarely is pulmonary fibrosis or non-bacterial pneumonia (pneumonitis).

Especially high cumulative doses increase the risk of secondary tumors, especially leukemia and bladder tumors.

Note(s)
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Like carmustine, lomustine crosses the blood-brain barrier and can therefore be successfully used against brain tumours (e.g. glioblastomas) (Wick W et al. 2017).

Literature
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  1. Graefe KH et al. non-selective cytotoxic chemotherapeutics (cytostatics) In: Graefe KH et al (Eds) Pharmacology and Toxicology. Georg Thieme Publisher Stuttgart S 667
  2. Taal W et al (2014) Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol 15:943-953.

  3. Wick W et al(2017) Lomustine and Bevacizumab in patients with progressive glioblastoma. N Engl J Med377:1954-1963.

Last updated on: 29.10.2020