OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Carmustine	154-93-8	C5-H9-Cl2-N3-O2

ANNOTATED BIBLIOGRAPHY

References updated: 17 January 2017

• Zimmerman HJ. Oncotherapeutic and immunosuppressive agents. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 673-708.

  (Expert review of hepatotoxicity of cancer chemotherapeutic agents published in 1999; mentions that carmustine has been linked to cases of hepatocellular injury with jaundice).
• DeLeve LD. Cancer chemotherapy. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 541-68.

  (Review of hepatotoxicity of cancer chemotherapeutic agents lists carmustine as having liver test elevations in up to 25% of patients and being linked to occasional case report of injury and even fatalities).
• Chabner BA, Bertino J, Clearly J, Ortiz T, Lane A, Supko JG, Ryan DP. Cytotoxic agents. Chemotherapy of neoplastic diseases. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 1677-730.

  (Textbook of pharmacology and therapeutics).
• De Vita VT, Carbone PP, Owens AH Jr, Gold GL, Krant MJ, Edmonson J. Clinical trials with 1,3-bis(2-chloroethyl)-1-nitrosourea, NSC-409962. Cancer Res 1965; 25: 1876-81. [PubMed: 5858571]

  (Preliminary studies of BCNU in 144 patients with malignancies using different dose schedules; AST elevations occurred in 15% after 13-63 days and were self-limited in all; liver toxicity may have contributed to the death of one patient).
• Hansen HH, Selawry OS, Muggia FM, Walker MD. Clinical studies with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (NSC 79037). Cancer Res 1971; 31: 223-7. [PubMed: 4926242]

  (Preliminary studies of CCNU in 40 patients with malignancies; there was no consistent hepatic dysfunction; AST elevations occurred in one patient).
• Young RC, De Vita VT, Serpick AA, Cancellos GP. Treatment of advanced Hodgkin's disease with [1,3-bis(2-chloroethyl)-1-nitrosourea] BCNU. N Engl J Med 1967; 285: 475-9. [PubMed: 5558887]

  (Among 45 patients with refractory Hodgkin disease treated with carmustine, 21 [47%] achieved a remission; mentions that one patient who died had liver toxicity).
• Walker MD, Hurwitz BS. BCNU(1,2-bis(2-chloroethyl)-1-nitrosourea; NSC-409962) in the treatment of malignant brain tumor- a preliminary report. Cancer Chemother Rep 1970; 54: 263-71. [PubMed: 4946011]

  (Pilot study of carmustine in 27 patients with brain tumors mentions that there were mild elevations in AST and Alk P in a few patients, but that these rapidly returned to normal).
• Lokich JJ, Drum DE, Kaplan W. Hepatic toxicity of nitrosourea analogues. Clin Pharmacol Ther 1974; 16: 363-7. [PubMed: 4852251]

  (2 cases: 70 year old man with metastatic colon cancer and cirrhosis developed jaundice 6 weeks after a 5 day course of carmustine and streptozotocin [bilirubin 6.2 mg/dL], but no other information given; 66 year old man with pancreatic cancer developed jaundice 2 weeks after carmustine and streptozotocin [bilirubin 3.5 mg/dL, AST 30 U/L, Alk P 135 U/L], with recovery after stopping therapy).
• Lessner HE, Vogler WR. Toxicity study of BCNU (NSC-409965) given orally. Cancer Chemother Rep 1974; 58: 407-11. [PubMed: 4601671]

  (Pilot study of carmustine alone in various oral doses in 104 patients with cancer; two patients developed liver toxicity, one with jaundice and elevated Alk P, but relationship to drug was considered uncertain).
• McIntyre RE, Magidson JG, Austin GE, Gale RP. Fatal veno-occlusive disease of the liver following high dose 1,3-bis(2-chloroethyl)-1-nitrosurea (BCNU) and autologus bone marrow transplantation. Am J Clin Pathol 1981; 75: 614-6. [PubMed: 7013473]

  (22 year old woman with lymphoma developed fatal sinusoidal obstruction syndrome arising 18 days after bone marrow transplantation, preceded by myeloablation using high dose carmustine alone).
• Brandes AA, Tosoni A, Amistà P, Nicolardi L, Grosso D, Berti F, Ermani M. How effective is BCNU in recurrent glioblastoma in the modern era? A phase II trial. Neurology 2004: 63: 1281-4. [PubMed: 15477552]

  (Among 40 patients with recurrent glioblastoma treated with 100 cycles of carmustine, hepatotoxicity [grade 2 or 3] occurred in 4 patients [10%], abnormalities resolving on average within 2 months of stopping).
• Wolff SN. High-dose carmustine and high-dose etoposide: a treatment regimen resulting in enhanced hepatic toxicity. Cancer Treat Rep 1986; 70: 1464-5. [PubMed: 3791261]

  (Pilot study of high dose carmustine and etoposide in 4 patients with astrocytoma; 3 developed hepatotoxicity with ascites arising 1-2 months after starting therapy which was fatal in 2).
• Phillips GL, Fay JW, Herzig GP, Herzig RH, Weiner RS, Wolff SN, Lazarus HM, et al. Intensive 1,3-bis(2-chloroethyl)-1-nitrosourea(BCNU), NSC #4366650 and cryopreserved autologous marrow transplantation for refractory cancer. A phase I-II study. Cancer 1983; 52: 1792-802. [PubMed: 6354414]

  (Among 93 patients with refractory cancer treated with escalating doses of carmustine and hematopoietic cell transplantation, hepatotoxicity occurred in 29 [31%], which was severe in 10 and fatal in 8 [9%], marked by cholestasis and hepatic failure with centrolobular hepatic necrosis and sinusoidal obstruction syndrome (SOS) in some cases, mostly with higher doses).
• Jones RJ, Lee KS, Beschorner WE, Vogel VG, Grochow LB, Braine HG, Vogelsang GB, et al. Veno-occlusive disease of the liver following bone marrow transplantation. Transplantation 1987; 4: 778-83. [PubMed: 3321587]

  (Among 235 patients undergoing hematopoietic cell transplantation between 1982 and 1985, sinusoidal obstruction syndrome [SOS] developed in 52 [22%] of whom half died, making SOS the third most common cause of death in this population).
• Ahmed T, Ciavarella D, Feldman E, Ascensao J, Hussain F, Engelking C, Gingrich S, et al. High-dose, potentially myeloablative chemotherapy and autologous bone marrow transplantation for patients with advanced Hodgkin's disease. Leukemia 1989; 3: 19-22. [PubMed: 2642573]

  (Among 23 patients with refractory Hodgkin disease treated with high doses of carmustine, etoposide and cyclophosphamide and autologous hematopoietic cell transplantation, 39% had liver test abnormalities and one died of hepatotoxicity; no details given).
• Jones RB, Shpall EJ, Ross M, Coniglio D, Affronti ML, Peters WP. High-dose carboplatin, cyclophosphamide, and BCNU with autologous bone marrow support: excessive hepatic toxicity. Cancer Chemother Pharmacol 1990; 26: 155-6. [PubMed: 2189592]

  (Among 4 patients given high dose carboplatin, cyclophosphamide and carmustine followed by hematopoietic cell transplantation for malignant melanoma, 3 developed severe SOS and two died and the fourth became jaundiced).
• Bearman SI. The syndrome of hepatic veno-occlusive disease after marrow transplantation. Blood 1995; 85: 3005-20. [PubMed: 7756636]

  (Review of sinusoidal obstruction syndrome after hematopoietic cell transplantation; usually presents with painful hepatomegaly, weight gain [fluid and ascites] and jaundice within 3 weeks of myeloablation, with occlusion of central veins and sinusoids and extensive zone 3 [centrolobular] injury).
• Papadakis V, Dunkel IJ, Cramer LD, Kramer E, Papadopoulos E, Goldman S, Packer RJ, et al. High-dose carmustine, thiotepa and etoposide followed by autologous bone marrow rescue for the treatment of high risk central nervous system tumors. Bone Marrow Transplant 2000; 26: 153-60. [PubMed: 10918425]

  (Among 42 patients with brain tumors who were treated with high dose carmustine, thiotepa and etoposide and autologous hematopoietic cell transplantation, 2 developed sinusoidal obstruction syndrome and 5 had transient elevations in ALT levels).
• DeLeve LD, Shulman HM, McDonald GB. Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome. Semin Liver Dis 2002; 22: 27-41. [PubMed: 11928077]

  (Review of clinical features, pathology, etiology, prevention and treatment of sinusoidal obstruction syndrome [SOS], a better term for this condition than veno-occlusive disease; first described in association with exposure to phytotoxins [pyrrolizidine alkaloids], the most common cause now is cancer chemotherapy and particularly myeloablative conditioning regimens in preparation for hematopoietic cell transplantation).
• McDonald GB. Hepatobiliary complications of hematopoietic cell transplantation, 40 years on. Hepatology 2010; 51: 1450-60. [PMC free article: PMC2914093] [PubMed: 20373370]

  (Review of liver complications of bone marrow [hematopoietic cell] transplantation, which have become less frequent with better understanding of their causes and means of prevention; the rate of SOS has decreased because of avoidance of more aggressive ablative therapies [total body irradiation and high doses of cyclophosphamide] and better understanding of pharmacokinetics of the alkylating agents).