Clinical and Histological Features of Idiosyncratic Acute Liver Injury Caused by Temozolomide
- 5 December 2012
- journal article
- case report
- Published by Springer Science and Business Media LLC in Digestive Diseases and Sciences
- Vol. 58 (5), 1415-1421
- https://doi.org/10.1007/s10620-012-2493-9
Abstract
To describe the clinical, biochemical and histological features of 4 patients with apparent hepatotoxicity due to temozolomide and to summarize the available literature of hepatotoxicity associated with this agent. Case series Patients were participants in the Drug-Induced Liver Injury Network a United States multicenter cooperative study. Four patients (ages 47 to 70 years; 3 men, 1 woman) developed liver injury 1 to 7 months after starting temozolomide chemotherapy. Discontinuation of temozolomide therapy. Among the first 1000 cases of drug-induced liver injury enrolled in a prospective U.S. multicenter database, 4 cases of temozolomide hepatotoxicity were identified (0.5%).Three were jaundiced and the initial pattern of serum enzyme elevations was often hepatocellular or mixed, but usually became cholestatic with time. Immunoallergic and autoimmune features were absent. Liver biopsies showed varying degrees of cholestasis, mild inflammation, focal hepatocellular injury and prominent bile duct damage or paucity. The liver injury tended to be prolonged and 3 patients still had liver tests abnormalities (one with jaundice) when they died of brain tumor or complications of its therapy 1 to 18 months later. Temozolomide hepatotoxicity although infrequent, can necessitate interruption of cancer chemotherapy and cause significant debility in already compromised patients.Keywords
This publication has 17 references indexed in Scilit:
- Patterns of Care and Survival in a Retrospective Analysis of 1059 Patients With Glioblastoma Multiforme Treated Between 2002 and 2007Neurosurgery, 2010
- Phase I/II dose escalation trial of concurrent temozolomide and whole brain radiation therapy for multiple brain metastasisJournal of Neuro-Oncology, 2010
- Causality assessment in drug-induced liver injury using a structured expert opinion process: Comparison to the Roussel-Uclaf causality assessment methodHepatology, 2010
- Temozolomide, a Novel Alkylating Agent with Activity in the Central Nervous System, May Improve the Treatment of Advanced Metastatic MelanomaThe Oncologist, 2000
- Enhancing hemopoietic drug resistance: A rationale for reconsidering the clinical use of mitozolomideCancer Gene Therapy, 2000
- Randomized Phase III Study of Temozolomide Versus Dacarbazine in the Treatment of Patients With Advanced Metastatic Malignant MelanomaJournal of Clinical Oncology, 2000
- Multicenter Phase II Trial of Temozolomide in Patients With Anaplastic Astrocytoma or Anaplastic Oligoastrocytoma at First RelapseJournal of Clinical Oncology, 1999
- Phase I trial of temozolomide (CCRG 81045: M&B 39831: NSC 362856)British Journal of Cancer, 1992
- Criteria of drug-induced liver disordersJournal of Hepatology, 1990
- Veno-occlusive liver disease after dacarbazine therapy (DTIC) for melanomaJournal of Surgical Oncology, 1984