OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Lomustine	13010-47-4	C9-H16-Cl-N3-O2

ANNOTATED BIBLIOGRAPHY

References updated: 03 June 2019

• 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 lomustine has been linked to serum aminotransferase elevations).
• DeLeve LD. Cancer chemotherapy. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 541-67.

  (Review of hepatotoxicity of cancer chemotherapeutic agents; lomustine is listed as an uncommon cause of liver injury but capable of causing sinusoidal obstruction syndrome at high doses).
• Wellstein A, Giaconne G, Atkins MB, Sausville EA. Cytotoxic agents. Chemotherapy of neoplastic diseases. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 20181, pp. 1167-1201.

  (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, including 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).
• 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).
• 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 uncertain).
• de Labarthe B, Chahinian P, Gosselin M, Goasguen J, Ferrand B, Danrigal A, Israel L. [Hepatic damage during treatment with C.C.N.U]. Sem Hop Ther 1975; 51: 309-14. French. [PubMed: 1224203]

  (50 year old woman with metastatic breast cancer developed jaundice during the fourth month of lomustine monotherapy [every 3 weeks], with bilirubin rising to 10.1 mg/dL, ALT 2900 U/L and Alk P 3-4 times ULN, ultimately recovered but died of metastatic disease several months later).
• 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 bone marrow 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).
• Kim L, Hochberg FH, Thornton AF, Harsh GR 4th, Patel H, Finkelstein D, Louis DN. Procarbazine, lomustine, and vincristine (PCV) chemotherapy for grade III and grade IV oligoastrocytomas. J Neurosurg 1996; 85: 602-7. [PubMed: 8814163]

  (Among 32 pateitns with astrocytotoma treated with a total of 124 cycles of procarbazine, lomustine and vincristine, there "were no reports of hepatic toxicity" and most dose adjustments were for hematologic toxicities).
• 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 sinusoidal obstruction syndrome 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; lomustine is not specifically discussed).
• Hernández N, Bessone F, Sánchez A, di Pace M, Brahm J, Zapata R, A Chirino R, et al. Profile of idiosyncratic drug induced liver injury in Latin America. An analysis of published reports. Ann Hepatol 2014; 13: 231-9. [PubMed: 24552865]

  (Systematic review of literature of drug induced liver injury in Latin American countries published from 1996 to 2012 identified 176 cases, 40 of which were attributed to antineoplastic agents, but none specifically to lomustine).
• Douros A, Bronder E, Andersohn F, Klimpel A, Thomae M, Sarganas G, Kreutz R, et al. Drug-induced liver injury: results from the hospital-based Berlin Case-Control Surveillance Study. Br J Clin Pharmacol 2015; 79: 988-99. [PMC free article: PMC4456131] [PubMed: 25444550]

  (Among 198 patients with hepatitis of uniknown cause enrolled in a prospective database from 51 Berlin hospitals between 2002 and 2011, none were attributed to lomustine).
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, 49 cases were attributed to antineoplastic agents, but none to lomustine).
• Jutras G, Bélanger K, Letarte N, Adam JP, Roberge D, Lemieux B, Lemieux-Blanchard É, et al. Procarbazine, lomustine and vincristine toxicity in low-grade gliomas. Curr Oncol 2018; 25: e33-e39. [PMC free article: PMC5832288] [PubMed: 29507493]

  (Among 57 patients treated with a regimen of procarbazine, lomustine and vincristine for low grade gliomas between 2005 and 2016, hematologic, hepatic and renal toxicities were common, ALT elevations arising in 65% of patients which were above 5 times ULN in 18%, but the major dose limiting toxicities were hematologic).