Fatal hepatic failure due to gemcitabine and vinorelbine
Authors: K. Kagohashi, Y. Funayama, H. Satoh, K. Sekizawa
Journal: Annals of Oncology (2003)

Gemcitabine and vinorelbine are indicated for the treatment of patients with inoperable non-small-cell lung carcinoma [1.Lilenbaum R. Cano R. Schwartz M. et al.Gemcitabine and vinorelbine in advanced nonsmall cell lung carcinoma a phase II study.Cancer. 2000; 88: 557-562Crossref PubMed Scopus (52) Google Scholar, 2.Lorusso V. Carpagnano F. Frasci G. et al.Phase I/II study of gemcitabine plus vinorelbine as first-line chemotherapy of non-small-cell lung cancer.J Clin Oncol. 2000; 18: 405-411Crossref PubMed Google Scholar]. We report fatal hepatic failure due to the combination of these two antitumor drugs in a patient with large cell carcinoma of the lung. A 57-year-old man was admitted for a nodular lesion in theleft lung noted on a chest X-ray. He had had laryngeal carcinoma 1 year previously, which was successfully treated with irradiation. He had no prior medical history of hepatic disease. A chest CT (computed tomography) scan showed a 4 cm nodule in the left lower lobe with bulky mediastinal lymph node swelling. Bronchoscopic biopsy revealed large cell carcinoma. Distant metastasis was not found, except for in lumbar bone. His liver function was normal. Subsequently, he was treated with gemcitabine 800 mg/m2and vinorelbine 20 mg/m2 (days 1 and 8). Ten days later, routine biochemical studies revealed abrupt elevation of serum alanine and aspartate aminotransferase concentrations to >1000 IU/l. Total bilirubin rose to 14.5 mg/dl (direct bilirubin 10.5 mg/dl). Abdominal ultrasonography showed neither dilated bile ducts nor intra-/extra-hepatic mass, which proved non-obstructive jaundice. Echocardiography ruled out heart failure. Viral markers for hepatitis were all negative. Because of his poor condition, liver biopsy was not performed. He died as a result of rapidly progressive hepatic failure 26 days after the initiation of the combined chemotherapy. Autopsy was not permitted. The main side-effect of these two antitumor drugs is myelosuppression. Congestive heart failure and pulmonary toxicity have also been reported [3.Gridelli C. Cigolari S. Gallo C. et al.Activity and toxicity of gemcitabine and gemcitabine + vinorelbine in advanced non-small-cell lung cancer elderly patients: phase II data from the Multicenter Italian Lung Cancer in the Elderly Study (MILES) randomized trial.Lung Cancer. 2001; 31: 277-284Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar]. It is well known that gemcitabine does not have severe toxicity; however, cases of liver injury that developed after treatment with gemcitabine were recently reported [4.Dobbie M. Hofer S. Oberholzer M. Herrmann R. Veno-occulusive disease of the liver induced by gemcitabine.Ann Oncol. 1998; 9: 681Abstract Full Text PDF PubMed Scopus (29) Google Scholar, 5.Coeman D.C. Verbeken E.K. Nackaerts K.L. et al.A fetal case of chelestatic liver failure probably related to gemcitabine.Ann Oncol. 2000; 11: 1503Abstract Full Text PDF PubMed Scopus (20) Google Scholar]. Fatal hepatic failure related to the combination of gemcitabine and vinorelbine has not previously been reported. The mechanism by which these two drugs may cause liver damage is not known. Regardless of the mechanism, however, physicians treating patients with these antitumor drugs should be alert to the possibility of fatal hepatic failure during the therapy. K. Kagohashi1, Y. Funayama1, H. Satoh2* & K. Sekizawa2 1Division of Respiratory Medicine, Tsukuba Gakuen Hospital and 2Instituteof Clinical Medicine, University of Tsukuba, Tsukuba-city, Ibaraki, Japan (*E-mail: [email protected])