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Bending the Curve Trial by Trial
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Nitrosoureas, triazenes, alkyl sulfonates, aziridines and related alkylatorsIn useSynthetic

Lomustine

Also known as CCNU, Gleostine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, NSC-79037

An oral chloroethyl nitrosourea taken as a single dose every six weeks. A current US label lists primary and metastatic brain tumours and, in combination, Hodgkin lymphoma that progressed after initial chemotherapy.

From discovery to approval

  1. 1968 · Earliest report found

    Lomustine (CCNU, NSC-79037) belongs to the nitrosourea series that a 1982 lecture by J. A. Montgomery credits to Southern Research Institute. The earliest paper found that names CCNU is a 1968 clinical brochure on BCNU and CCNU; whether the 1963 or 1966 synthesis papers describe CCNU is unconfirmed.[2][3][4][5][6]

  2. 1976-08-04 · FDA regular · 8 years after first description

    Lomustine capsules, NDA 017588, original approval, classed as a new molecular entity with standard review in the Drugs@FDA history. The original label and letter are not available there, so the indication at approval is not stated here; a current label lists primary and metastatic brain tumours and Hodgkin lymphoma. The type regular is an inference: no accelerated-approval wording was found.[7]

How it works

A chloroethylating nitrosourea: this group alkylates DNA, first forming single-base adducts and then interstrand crosslinks that block replication and transcription. The US label says lomustine alkylates DNA and RNA and may also inhibit enzymes by carbamoylating proteins.[1]

Where it came from and why

The sources read do not say why CCNU was made. A 1976 review states that the nitrosoureas showed anticancer activity by oral as well as parenteral routes, and an oral capsule is how lomustine is now given.

Cancers

  • Brain tumours

    The current US label lists primary and metastatic brain tumours following appropriate surgical or radiotherapeutic procedures. A 1972 phase II study treated 38 patients with recurrent primary or metastatic brain tumours.[8]

  • Recurrent glioblastoma

    Lomustine was the control arm of the EORTC 26101 trial of lomustine with or without bevacizumab at first progression of glioblastoma.[9]

  • Anaplastic oligodendroglioma and low-grade glioma (PCV regimen)

    Lomustine is the L in procarbazine, lomustine and vincristine (PCV), which was added to radiotherapy in randomised trials in anaplastic oligodendroglioma and in grade 2 glioma.[10]

  • Hodgkin lymphoma

    The current US label lists Hodgkin lymphoma in combination with other chemotherapy, after disease progression following initial chemotherapy.[8]

Worth knowing

  • In a 1972 phase II study of 38 patients with recurrent brain tumours, the response rate was 33% in patients with no prior chemotherapy and 0 in patients previously treated with BCNU, and the authors concluded that cross-resistance to CCNU occurred in patients previously treated with BCNU.[11]
  • In EORTC 26101 (437 patients), median overall survival was 9.1 months with lomustine plus bevacizumab and 8.6 months with lomustine alone (hazard ratio for death 0.95; 95% CI 0.74 to 1.21; P = 0.65).[9]
  • In the CeTeG/NOA-09 trial in glioblastoma with a methylated MGMT promoter, median overall survival was 48.1 months with lomustine plus temozolomide and 31.4 months with temozolomide (hazard ratio 0.60; 95% CI 0.35 to 1.03); the authors advise caution because the trial was small.[12]
  • In a long-term report of a randomised trial of radiotherapy with or without PCV in grade 2 glioma (251 patients), median overall survival was 13.3 years with radiotherapy plus chemotherapy and 7.8 years with radiotherapy alone (hazard ratio for death 0.59; P = 0.003).[13]
  • The current US label specifies one oral dose of 130 mg per square metre every 6 weeks and tells prescribers to dispense only enough capsules for a single dose.[8]

On this site

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. Montgomery JA. Has the well gone dry? The First Cain Memorial Award Lecture. Cancer Res. 1982;42(10):3911-7. PubMed
  3. Johnston TP, McCaleb GS, Opliger PS, Montgomery JA. The synthesis of potential anticancer agents. XXXVI. N-nitrosoureas. II. Haloalkyl derivatives. J Med Chem. 1966;9(6):892-911. PubMedDOI
  4. Carter SK, Newman JW. Nitrosoureas: 1,3-bis(2-chloroethyl)-1-nitrosourea (NSC-409962; BCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (NSC-79037; CCNU)--clinical brochure. Cancer Chemother Rep 3. 1968;1(1):115-51. PubMed
  5. Hansen HH, Selawry OS, Muggia FM, Walker MD. Clinical studies with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (NSC 79037). Cancer Res. 1971;31(3):223-7. PubMed
  6. Schabel FM Jr. Nitrosoureas: a review of experimental antitumor activity. Cancer Treat Rep. 1976;60(6):665-98. PubMed
  7. U.S. Food and Drug Administration. Drugs@FDA: Approval date(s) and history, letters, labels, reviews for NDA 017588 (lomustine; Gleostine). Page read 2026-10-26. Source
  8. Azurity Pharmaceuticals, Inc. Gleostine (lomustine) capsules: prescribing information. DailyMed, set ID 3529fe2f-3c23-4862-bb20-b48026957082, published 17 November 2025. Source
  9. Wick W, Gorlia T, Bendszus M, Taphoorn M, Sahm F, Harting I, et al. Lomustine and Bevacizumab in Progressive Glioblastoma. N Engl J Med. 2017;377(20):1954-1963. PubMedDOI
  10. van den Bent MJ, Brandes AA, Taphoorn MJ, Kros JM, Kouwenhoven MC, Delattre JY, et al. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol. 2013;31(3):344-50. PubMedDOI
  11. Fewer D, Wilson CB, Boldrey EB, Enot JK. Phase II study of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU; NSC-79037) in the treatment of brain tumors. Cancer Chemother Rep. 1972;56(3):421-7. PubMed
  12. Herrlinger U, Tzaridis T, Mack F, Steinbach JP, Schlegel U, Sabel M, et al. Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG/NOA-09): a randomised, open-label, phase 3 trial. Lancet. 2019;393(10172):678-688. PubMedDOI
  13. Buckner JC, Shaw EG, Pugh SL, Chakravarti A, Gilbert MR, Barger GR, et al. Radiation plus Procarbazine, CCNU, and Vincristine in Low-Grade Glioma. N Engl J Med. 2016;374(14):1344-55. PubMedDOI