Skip to content
Bending the Curve Trial by Trial
?

Nitrosoureas, triazenes, alkyl sulfonates, aziridines and related alkylatorsIn useSynthetic

Carmustine

Also known as BiCNU, BCNU, Gliadel, 1,3-bis(2-chloroethyl)-1-nitrosourea, NSC-409962

A chloroethyl nitrosourea given by intravenous infusion, and as a biodegradable implant placed in the brain at surgery. A current US label lists brain tumours, multiple myeloma and relapsed Hodgkin and non-Hodgkin lymphomas.

From discovery to approval

  1. 1964 · Earliest report found

    A 1982 lecture by J. A. Montgomery says research at Southern Research Institute led to the nitrosoureas as a class of anticancer agents. Papers titled as N-nitrosourea syntheses, first-authored by T. P. Johnston, appeared in 1963 and 1966. The earliest paper found that names carmustine is a 1964 tissue-distribution study of labelled BCNU.[2][3][4][5][6]

  2. 1977-03-07 · FDA regular · 13 years after first description

    Carmustine for injection (BiCNU), NDA 017422, 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 brain tumours, multiple myeloma and relapsed Hodgkin and non-Hodgkin lymphomas as palliative therapy. The type regular is an inference: no accelerated-approval wording was found.[7]

  3. 1996-09-23 · FDA regular · 32 years after first description

    Gliadel (carmustine) intracranial implant, NDA 020637, original approval classed as Type 3 (new dosage form) with priority review and orphan status in the Drugs@FDA history. Only the history page was read; the indication at approval is not stated here. The type regular is an inference: no accelerated-approval wording was found.[8]

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 carmustine's mechanism is not fully understood and that it may also carbamoylate proteins.[1]

Where it came from and why

The sources read do not say why the nitrosoureas were first made. A 1976 review reports that they were the most active drug group seen against experimental meningeal leukaemias and intracerebral tumours in mice and hamsters, which is consistent with their later use in brain tumours.

Cancers

  • Brain tumours

    The current US label lists glioblastoma, brainstem glioma, medulloblastoma, astrocytoma, ependymoma and metastatic brain tumours, as palliative therapy alone or in established combinations. A 1978 randomised trial tested BCNU with or without radiotherapy in anaplastic glioma.[9]

  • Malignant glioma (biodegradable implant)

    Carmustine-impregnated biodegradable polymer discs were tested in recurrent malignant glioma in a placebo-controlled trial (1995) and as wafers at primary resection in newly diagnosed malignant glioma (2003).[10]

  • Multiple myeloma

    The current US label lists multiple myeloma, in combination with prednisone.[9]

  • Hodgkin and non-Hodgkin lymphomas

    The current US label lists relapsed or refractory Hodgkin lymphoma and relapsed or refractory non-Hodgkin lymphomas, in combination with other approved drugs.[9]

  • Central nervous system leukaemia and solid tumours of childhood

    A 1966 paper is titled as treating central nervous system leukaemia and solid tumours of childhood with BCNU; only the title was read.[11]

Worth knowing

  • In a 1978 randomised trial of 303 patients with anaplastic glioma, the median survival in the valid study group was 14 weeks with best conventional care, 18.5 weeks with BCNU, 35 weeks with radiotherapy and 34.5 weeks with BCNU plus radiotherapy.[12]
  • In a placebo-controlled trial of 222 patients with recurrent malignant glioma, median survival was 31 weeks with carmustine polymer discs and 23 weeks with placebo discs (hazard ratio 0.67, p = 0.006, after accounting for prognostic factors).[10]
  • In a trial of 240 patients given carmustine or placebo wafers at primary resection plus radiotherapy, median survival in the intention-to-treat group was 13.9 months with carmustine wafers and 11.6 months with placebo wafers (stratified log-rank p = 0.03).[13]
  • The current US label states that carmustine crosses the blood-brain barrier, with radioactivity in cerebrospinal fluid at 50% or more of the concurrent plasma level.[9]

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, MONTGOMERY JA. THE SYNTHESIS OF ANTINEOPLASTIC AGENTS. XXXII. N-NITROSOUREAS. I. J Med Chem. 1963;6:669-81. PubMedDOI
  4. 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
  5. WHEELER GP, BOWDON BJ, HERREN TC. DISTRIBUTION OF C14 FROM C14-LABELED 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA (NSC-409962) IN TISSUES OF MICE AND HAMSTERS AFTER INTRAPERITONEAL ADMINISTRATION OF THE AGENT. Cancer Chemother Rep. 1964;42:9-12. 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 017422 (carmustine; BiCNU). Page read 2026-10-26. Source
  8. U.S. Food and Drug Administration. Drugs@FDA: Approval date(s) and history, letters, labels, reviews for NDA 020637 (carmustine implant; Gliadel). Page read 2026-10-26. Source
  9. Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc. Carmustine for injection: prescribing information. DailyMed, set ID b9b47082-32ee-4abb-a7b2-52292894d3f8, published 13 April 2026 (label text revised 10/2024). Source
  10. Brem H, Piantadosi S, Burger PC, Walker M, Selker R, Vick NA, et al. Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-brain Tumor Treatment Group. Lancet. 1995;345(8956):1008-12. PubMedDOI
  11. Iriarte PV, Hananian J, Cortner JA. Central nervous system leukemia and solid tumors of childhood. Treatment with 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU). Cancer. 1966;19(9):1187-94. PubMedDOI
  12. Walker MD, Alexander E Jr, Hunt WE, MacCarty CS, Mahaley MS Jr, Mealey J Jr, et al. Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J Neurosurg. 1978;49(3):333-43. PubMedDOI
  13. Westphal M, Hilt DC, Bortey E, Delavault P, Olivares R, Warnke PC, et al. A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro Oncol. 2003;5(2):79-88. PubMedDOI