PHARMACOKINETICS OF ANTICANCER AGENTS IN PATIENTS WITH IMPAIRED LIVER-FUNCTION

This report reviews published information on the clinical pharmacokine tics of antitumour agents in patients with liver dysfunction, associat ed with primary liver disease or liver metastases. Information was ava ilable for anthracyclines and their related compounds, antimetabolites , cyclophosphamide, vinca alkaloids, taxanes and epipodophyllotoxins. Changes in the pharmacokinetic profile or metabolism in patients with mild or severe hepatobiliary dysfunction are described and the relatio nships between serum levels, parameters employed for measuring hepatic function and toxic or therapeutic effects are examined. Current knowl edge of the pharmacokinetics of antineoplastic agents in liver disease is far from complete, mostly obtained in small numbers of non-homogen eous patients often presenting only moderate liver dysfunction, and em pirical guidelines for dose assessment are still largely applied in cl inical practice. Because of the complex pathophysiological mechanisms of liver insufficiency in cancer patients, there is still doubt whethe r endogenous markers are useful. Although caution in treating cancer p atients with liver insufficiency is compulsory, for most compounds the re seems no need to recommend dose reductions for moderate impairment. However, for the tubulin acting agents, vincristine, vinblastine and possibly for paclitaxel and docetaxel, there is strong evidence that d ose adjustment is mandatory in order to avoid excessive neutropenia an d neurotoxicity. (C) 1998 Elsevier Science Ltd.