Toxicities of gemcitabine in patients with severe hepatic dysfunction

To determine the relationship between doses of gemcitabine and absolute neutrophil count and thrombocytopenia in patients with severe hepatic dysfunction (total bilirubin > or =4.5 mg/dL), and the relationship between doses of gemcitabine in patients with severe hepatic dysfunction and nonhematologic toxicity.

A retrospective chart review was conducted for patients receiving gemcitabine at the Medical University of South Carolina from October 2006 through October 2008. Seven patients were identified who had an elevated total bilirubin level (> or =4.5 mg/dL) at the time they were receiving gemcitabine. All 7 patients received gemcitabine 1000 mg/m(2) throughout their treatment, regardless of liver function. Six patients did not experience significant hematologic toxicity warranting a dose reduction or a dose being held. One patient developed thrombocytopenia, warranting a dose being held.

Gemcitabine is a chemotherapy agent frequently used for the treatment of pancreatic cancer as well as metastatic breast, lung, and ovarian cancer. To date there is limited information on dosing of gemcitabine in patients with an elevated total bilirubin. A previous study looking at lower grades of liver dysfunction suggested empiric dose reductions be made in these patients because of increased incidence of toxicity.

These results indicate the possibility that no initial dose reduction is necessary for patients with liver dysfunction receiving gemcitabine; however, close monitoring of these patients is required.