FLUTAMIDE-INDUCED LIVER TOXICITY INCLUDING FATAL HEPATIC-NECROSIS

Purpose: To describe hepatic injuries in three patients who received f lutamide prior to and during radiation treatment to make radiation onc ologists aware of the need for careful monitoring of liver function du ring use of this drug. Methods and Materials: The records of three pat ients who developed abnormal liver function tests while undergoing tot al androgen suppression (TAS) as well as the literature concerning flu tamide toxicity were reviewed and summarized. Results: Three of 34 pat ients treated with a TAS regimen incorporating flutamide developed sig nificant hepatic abnormalities: elevated transaminases [2] and fatal h epatic necrosis [1], Following the discontinuation of flutamide, two p atients recovered fully. Unfortunately, the third patient's hepatic fu nction continued to deteriorate, which culminated in his death, Transi ent elevations in serum transaminases, which do not exceed four times the upper limits of normal, are common and apparently without clinical significance, Unfortunately, idiosyncratic serious and/or fatal liver damage can occur, Significant liver toxicity may be obviated by monit oring of liver function tests (LFT) early in the course of flutamide t herapy. Conclusion: The incidence of hepatic toxicity associated with flutamide may be higher than previously suggested, To prevent the deve lopment of serious hepatic dysfunction, all patients receiving flutami de should be monitored clinically for signs and symptoms referable to hepatic injury and with serial LFT, We recommend baseline LFT followed by serial LFT at weeks 2, 4, 6, and 8 from the start of treatment wit h flutamide, Flutamide should be stopped promptly if significant liver abnormalities are detected.