| Summary: | 碩士 === 國立臺灣大學 === 臨床藥學研究所 === 93 === Gemcitabine (Gemzar®) is one of the standard drugs used in patients with advanced non-small cell lung cancer. Compared with other cytotoxic agents, gemcitabine displayed minimal toxicity. Hepatotoxicity occurred frequently (about 20~50%) and was manifest as a transient, asymptomatic, rapidly reversible elevation of liver enzymes. However, several case reports have revealed that gemcitabine may cause serious hepatotoxicity such as hepatic veno-occlusive disease, cholestatic liver failure and hepatitis B virus reactivation.
This retrospective study was conducted to review the use of first-line gemcitabine for non-small cell lung cancer in a tertiary medical center. The aim of this study was to investigate the incidence, severity and risk factors of hepatitis caused by gemcitabine and its influence on treatment outcome; the incidence and treatment of hepatitis B virus reactivation induced by gemcitabine. For those who treated with second-line chemotherapy, this study also sought to find out the risk factors of hepatitis caused by these agents.
Three hundreds thirty-seven patients were assessable. Most patients were treated with single gemcitabine or gemcitabine-cisplatin combination. The overall response rate was 19% and the median survival was 11 months.
After gemcitabine treatment, WHO grade 1/2 and 3/4 hepatotoxicity was recorded in nearly 30% and 5% of patients, respectively. Among these patients, hepatitis B carriers were more likely to have serious hepatotoxicity (WHO grade 3/4) than non-carriers. The extent of elevation of alanine transaminase in 88 patients (26.1%) was identical to the definition of hepatitis. There was no evidence of dose-cumulative hepatitis and its occurrence was not related to response rate and survival time. In univariate analysis, the predictors of hepatitis were female, young age, hepatitis B carriers and regimen without steroid.
Though the only case having hepatitis B virus reactivation was treated with lamivudine immediately after abnormal liver function test, she died of hepatic encephalopathy 72 days following the initiation of gemcitabine treatment. The probable reason was that lamivudine may not be effective in reducing liver injury by this time. It may be more effective in earlier phase of active viral replication.
The incidence of hepatitis caused by second-line chemotherapy (11.7%) was much lower than that induced by gemcitabine. There was no specific drug that most likely to cause hepatitis. Also, hepatitis B or C virus infection and the experience of hepatitis in gemcitabine treatment were not predictive of the occurrence of hepatitis.
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