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Chemical Compound Review

Nitrumon     1,3-bis(2-chloroethyl)-1- nitroso-urea

Synonyms: Becenum, Becenun, Carmubris, carmustine, BiCNU, ...
 
 
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Disease relevance of carmustine

  • Symptomatic pulmonary disease occurred in 20 per cent of 93 patients with anaplastic gliomas being treated with carmustine (BCNU) [1].
  • An equation has been generated that allows prediction of pulmonary toxicity during the course of therapy with BCNU with 80 per cent accuracy [1].
  • To investigate the clinical range of this side effect, we studied the survivors among 31 children treated with carmustine for brain tumors between 1972 and 1976 [2].
  • Carmustine (BCNU) is an anticancer drug known to produce pulmonary fibrosis as a side effect within three years of treatment [2].
  • Carmustine chemotherapy in childhood causes lung fibrosis that may remain asymptomatic for many years or become symptomatic at any time [2].
  • Although systemically administered O6-BG can be coadministered with Gliadel wafers safely, it may increase the risk of hydrocephalus, CSF leak, and CSF/brain infection [3].
 

Psychiatry related information on carmustine

  • Intensive monochemotherapy with carmustine (BCNU) (either 1,050, 1,200, or 1,350 mg/m2) and cryopreserved autologous marrow transplantation was administered to 36 patients with malignant glioma: 27 with progressive disease and nine without progression (adjuvant therapy group) [4].
  • Treatment of air-breathing rats with carmustine (12.5, 25 and 50 mg/kg i.v.) resulted in a dose-dependent decrease (P less than .001) in whole-brain glutathione reductase activity without affecting the activities of the other components of the antioxidant defense mechanisms determined [5].
  • Transient confusion with disorientation was observed in two patients 4 and 24 hours, respectively, after a BCNU infusion [6].
  • OBJECTIVE: This article presents a review of the information presently available on BCNU wafers-both pro and con-to aid in the clinical decision-making process [7].
 

High impact information on carmustine

 

Chemical compound and disease context of carmustine

 

Biological context of carmustine

  • An analysis of the variables has revealed a relation between the occurrence of pulmonary toxicity on the one hand, and the total cumulative dose of BCNU, the number of cycles over which the BCNU was administered, the history of lung disease, the patient's age, and the platelet-count nadir after the first course of BCNU on the other [1].
  • PURPOSE: The purpose of this study was to analyze clinical and pharmacokinetic data from our ongoing phase II trials and to determine whether there is an association between BCNU pharmacokinetics and acute lung injury following cyclophosphamide-cisplatin-BCNU therapy [14].
  • PURPOSE: The purpose of this phase I study was to determine (a) the maximum tolerated dose (MTD) of carmustine (BCNU), a CENU, plus a fixed dose of STZ; (b) the toxic effects of the drugs; and (c) the effects on peripheral blood mononuclear cells (PBMC) [18].
  • RESULTS: Diffusion MRI could detect water diffusion changes in orthotopic 9L gliomas after doses of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU or carmustine) that resulted in as little as 0.2 log cell kill, a measure of tumor cell death [19].
  • Twelve (60%) of the 20 had values for area under the curve (AUC) for BCNU concentration x time that exceeded 600 (micrograms/mL) x minute, whereas only two (11%) of the 18 without pulmonary injury had values above this level (P < .03) [14].
 

Anatomical context of carmustine

 

Associations of carmustine with other chemical compounds

 

Gene context of carmustine

 

Analytical, diagnostic and therapeutic context of carmustine

References

  1. Prediction of BCNU pulmonary toxicity in patients with malignant gliomas: an assessment of risk factors. Aronin, P.A., Mahaley, M.S., Rudnick, S.A., Dudka, L., Donohue, J.F., Selker, R.G., Moore, P. N. Engl. J. Med. (1980) [Pubmed]
  2. Active lung fibrosis up to 17 years after chemotherapy with carmustine (BCNU) in childhood. O'Driscoll, B.R., Hasleton, P.S., Taylor, P.M., Poulter, L.W., Gattameneni, H.R., Woodcock, A.A. N. Engl. J. Med. (1990) [Pubmed]
  3. Phase II trial of Gliadel plus O6-benzylguanine in adults with recurrent glioblastoma multiforme. Quinn, J.A., Jiang, S.X., Carter, J., Reardon, D.A., Desjardins, A., Vredenburgh, J.J., Rich, J.N., Gururangan, S., Friedman, A.H., Bigner, D.D., Sampson, J.H., McLendon, R.E., Herndon, J.E., Threatt, S., Friedman, H.S. Clin. Cancer Res. (2009) [Pubmed]
  4. Intensive 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) monochemotherapy and autologous marrow transplantation for malignant glioma. Phillips, G.L., Wolff, S.N., Fay, J.W., Herzig, R.H., Lazarus, H.M., Schold, C., Herzig, G.P. J. Clin. Oncol. (1986) [Pubmed]
  5. Effect of inhibition of glutathione reductase by carmustine on central nervous system oxygen toxicity. Powell, S.R., Puglia, C.D. J. Pharmacol. Exp. Ther. (1987) [Pubmed]
  6. Phase II study--intra-arterial BCNU therapy for metastatic brain tumors. Madajewicz, S., West, C.R., Park, H.C., Ghoorah, J., Avellanosa, A.M., Takita, H., Karakousis, C., Vincent, R., Caracandas, J., Jennings, E. Cancer (1981) [Pubmed]
  7. The role of interstitial BCNU chemotherapy in the treatment of malignant glioma. Engelhard, H.H. Surgical neurology. (2000) [Pubmed]
  8. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. Esteller, M., Garcia-Foncillas, J., Andion, E., Goodman, S.N., Hidalgo, O.F., Vanaclocha, V., Baylin, S.B., Herman, J.G. N. Engl. J. Med. (2000) [Pubmed]
  9. Carmustine as a cause of acute nonlymphocytic leukemia. Greene, M.H., Boice, J.D., Strike, T.A. N. Engl. J. Med. (1985) [Pubmed]
  10. Vitamin E reversal of the effect of extracellular calcium on chemically induced toxicity in hepatocytes. Fariss, M.W., Pascoe, G.A., Reed, D.J. Science (1985) [Pubmed]
  11. Effect of cell-cell interactions on drug sensitivity and growth of drug-sensitive and -resistant tumor cells in spheroids. Tofilon, P.J., Buckley, N., Deen, D.F. Science (1984) [Pubmed]
  12. Electroacupuncture for control of myeloablative chemotherapy-induced emesis: A randomized controlled trial. Shen, J., Wenger, N., Glaspy, J., Hays, R.D., Albert, P.S., Choi, C., Shekelle, P.G. JAMA (2000) [Pubmed]
  13. High-dose tri-alkylator chemotherapy with autologous stem cell rescue in patients with refractory malignancies. Moormeier, J.A., Williams, S.F., Kaminer, L.S., Garner, M., Bitran, J.D. J. Natl. Cancer Inst. (1990) [Pubmed]
  14. Acute lung injury following treatment with high-dose cyclophosphamide, cisplatin, and carmustine: pharmacodynamic evaluation of carmustine. Jones, R.B., Matthes, S., Shpall, E.J., Fisher, J.H., Stemmer, S.M., Dufton, C., Stephens, J.K., Bearman, S.I. J. Natl. Cancer Inst. (1993) [Pubmed]
  15. Modified chemotherapy with carmustine, cytarabine, cyclophosphamide, and 6-thioguanine (BACT) and autologous bone marrow transplantation in 24 poor-risk patients with acute lymphoblastic leukemia. Pico, J.L., Hartmann, O., Maraninchi, D., Beaujean, F., Benhamou, E., Mascret, B., Novakovitch, G., Ghalie, R., Kalifa, C., Hayat, M. J. Natl. Cancer Inst. (1986) [Pubmed]
  16. Gastric cancer: current status of treatment. Carter, S.K., Comis, R.L. J. Natl. Cancer Inst. (1977) [Pubmed]
  17. Novobiocin enhances alkylating agent cytotoxicity and DNA interstrand crosslinks in a murine model. Eder, J.P., Teicher, B.A., Holden, S.A., Cathcart, K.N., Schnipper, L.E. J. Clin. Invest. (1987) [Pubmed]
  18. Phase I study of streptozocin- and carmustine-sequenced administration in patients with advanced cancer. Micetich, K.C., Futscher, B., Koch, D., Fisher, R.I., Erickson, L.C. J. Natl. Cancer Inst. (1992) [Pubmed]
  19. Diffusion magnetic resonance imaging: an early surrogate marker of therapeutic efficacy in brain tumors. Chenevert, T.L., Stegman, L.D., Taylor, J.M., Robertson, P.L., Greenberg, H.S., Rehemtulla, A., Ross, B.D. J. Natl. Cancer Inst. (2000) [Pubmed]
  20. In vivo selection of MGMT(P140K) lentivirus-transduced human NOD/SCID repopulating cells without pretransplant irradiation conditioning. Zielske, S.P., Reese, J.S., Lingas, K.T., Donze, J.R., Gerson, S.L. J. Clin. Invest. (2003) [Pubmed]
  21. Repair-deficient 3-methyladenine DNA glycosylase homozygous mutant mouse cells have increased sensitivity to alkylation-induced chromosome damage and cell killing. Engelward, B.P., Dreslin, A., Christensen, J., Huszar, D., Kurahara, C., Samson, L. EMBO J. (1996) [Pubmed]
  22. Chemosensitivity testing in V79 spheroids: drug delivery and cellular microenvironment. Durand, R.E. J. Natl. Cancer Inst. (1986) [Pubmed]
  23. Enhancement of nitrosourea activity in medulloblastoma and glioblastoma multiforme. Friedman, H.S., Dolan, M.E., Moschel, R.C., Pegg, A.E., Felker, G.M., Rich, J., Bigner, D.D., Schold, S.C. J. Natl. Cancer Inst. (1992) [Pubmed]
  24. Sensitivity of proliferating cultured murine pancreatic tumor cells to selected antitumor agents. Wilkoff, L.J., Dulmadge, E.A. J. Natl. Cancer Inst. (1986) [Pubmed]
  25. The epidermal growth factor receptor pathway mediates resistance to sequential administration of radiation and chemotherapy in primary human glioblastoma cells in a RAS-dependent manner. Chakravarti, A., Chakladar, A., Delaney, M.A., Latham, D.E., Loeffler, J.S. Cancer Res. (2002) [Pubmed]
  26. Mismatch repair mutations override alkyltransferase in conferring resistance to temozolomide but not to 1,3-bis(2-chloroethyl)nitrosourea. Liu, L., Markowitz, S., Gerson, S.L. Cancer Res. (1996) [Pubmed]
  27. Endogenous defenses against the cytotoxicity of hydrogen peroxide in cultured rat hepatocytes. Starke, P.E., Farber, J.L. J. Biol. Chem. (1985) [Pubmed]
  28. Inactivated MGMT by O6-benzylguanine is associated with prolonged G2/M arrest in cancer cells treated with BCNU. Yan, L., Donze, J.R., Liu, L. Oncogene (2005) [Pubmed]
  29. Cloning and expression of canine O6-methylguanine-DNA methyltransferase in target cells, using gammaretroviral and lentiviral vectors. Zaboikin, M., Srinivasakumar, N., Zaboikina, T., Schuening, F. Hum. Gene Ther. (2004) [Pubmed]
  30. Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. Walker, M.D., Green, S.B., Byar, D.P., Alexander, E., Batzdorf, U., Brooks, W.H., Hunt, W.E., MacCarty, C.S., Mahaley, M.S., Mealey, J., Owens, G., Ransohoff, J., Robertson, J.T., Shapiro, W.R., Smith, K.R., Wilson, C.B., Strike, T.A. N. Engl. J. Med. (1980) [Pubmed]
  31. Growth and rejection of leukemia cells in individual mice after combined treatment with amphotericin B and 1,3-bis(2-chloroethyl)-1-nitrosourea. Valeriote, F., Lynch, R., Medoff, G., Tolen, S., Dieckman, J. J. Natl. Cancer Inst. (1978) [Pubmed]
 
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