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Bending the Curve Trial by Trial
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Nitrosoureas, triazenes, alkyl sulfonates, aziridines and related alkylatorsUsed in a few countriesSyntheticNeeds review

Nimustine

Also known as ACNU, nimustine hydrochloride

A water-soluble chloroethyl nitrosourea known as ACNU. A Japanese trial used it with radiotherapy in glioma, and a 2017 review lists it among the chloroethylating nitrosoureas used for gliomas.

From discovery to approval

  1. 1975 · Earliest report found

    The earliest record found is a 1975 report in the journal Gan testing ACNU, a water-soluble nitrosourea, against L1210 leukaemia in mice. Its developers and first synthesis were not traced.[2]

  2. No approval is recorded on this site.

How it works

A chloroethylating nitrosourea: this group alkylates DNA, first forming single-base adducts and then interstrand crosslinks that block replication and transcription. A trial report notes that resistance to nimustine has been linked to the repair enzyme MGMT.[1]

Where it came from and why

The sources read do not say why it was made. The 1975 report found the highest therapeutic ratio of all drugs tested and activity by injection into the peritoneum or a vein or by mouth in leukaemic mice.

Cancers

  • Glioma

    The JCOG0305 trial in Japan randomised 111 patients with newly diagnosed anaplastic astrocytoma or glioblastoma to radiotherapy with ACNU alone or with ACNU plus procarbazine; the 2017 review of chloroethylating nitrosoureas lists nimustine for gliomas.[3]

  • Lung cancer

    A 1978 paper is titled as testing ACNU in primary lung cancer, mesothelioma and metastatic pulmonary tumours (title only), and a 1979 report tested it in a transplanted lung carcinoma in animals.[4]

Worth knowing

  • In JCOG0305, stopped early after temozolomide was newly approved in Japan, median overall survival was 27.4 months with ACNU alone (n = 55) and 22.4 months with ACNU plus procarbazine (n = 56; p = 0.75); the authors concluded that adding procarbazine was not beneficial.[3]
  • In a 1979 animal study, ACNU given in a large single dose was highly effective against Sato lung carcinoma and its action depended on tumour size.[5]

References

  1. Nikolova T, Roos WP, Krämer OH, Strik HM, Kaina B. Chloroethylating nitrosoureas in cancer therapy: DNA damage, repair and cell death signaling. Biochim Biophys Acta Rev Cancer. 2017;1868(1):29-39. PubMedDOI
  2. Shimizu F, Arakawa M. Effect of 3-[4-amino-2-methyl-5-pyrimidinyl)ethyl[-1(2-chloroethyl)-1-nitrosourea hydrochloride on lymphoid leukemia L-1210. Gan. 1975;66(2):149-54. PubMed
  3. Shibui S, Narita Y, Mizusawa J, Beppu T, Ogasawara K, Sawamura Y, et al. Randomized trial of chemoradiotherapy and adjuvant chemotherapy with nimustine (ACNU) versus nimustine plus procarbazine for newly diagnosed anaplastic astrocytoma and glioblastoma (JCOG0305). Cancer Chemother Pharmacol. 2013;71(2):511-21. PubMedDOI
  4. Saijo N, Nishiwaki Y, Kawase I, Kobayashi T, Suzuki A, Niitani H. Effect of ACNU on primary lung cancer, mesothelioma, and metastatic pulmonary tumors. Cancer Treat Rep. 1978;62(1):139-41. PubMed
  5. Saijo N, Niitani H, Irimajiri N, Chikama M. Effect of 1(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) on Sato lung carcinoma (SLC). Preliminary result of immunochemotherapy for SLC by combination of ACNU and Propionibacterium acnes. Oncology. 1979;36(1):7-10. PubMed