Pharmacokinetics of anticancer agents in patients with impaired liver function.
This report reviews published information on the clinical pharmacokinetics of antitumour agents in patients with liver dysfunction, associated with primary liver disease or liver metastases. Information was available 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 relationships between serum levels, parameters employed for measuring hepatic function and toxic or therapeutic effects are examined. Current knowledge of the pharmacokinetics of antineoplastic agents in liver disease is far from complete, mostly obtained in small numbers of non-homogeneous patients often presenting only moderate liver dysfunction, and empirical guidelines for dose assessment are still largely applied in clinical practice. Because of the complex pathophysiological mechanisms of liver insufficiency in cancer patients, there is still doubt whether endogenous markers are useful. Although caution in treating cancer patients with liver insufficiency is compulsory, for most compounds there 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 dose adjustment is mandatory in order to avoid excessive neutropenia and neurotoxicity.
Donelli
M G
MG
Dipartimento di Oncologia, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Zucchetti
M
M
Munzone
E
E
D'Incalci
M
M
Crosignani
A
A
D018943:Anthracyclines / Q000493:pharmacokinetics*; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D003520:Cyclophosphamide / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000493:pharmacokinetics; D006801:Humans; D008107:Liver Diseases / Q000378:metabolism*; D017239:Paclitaxel / Q000493:pharmacokinetics; D011034:Podophyllotoxin / Q000493:pharmacokinetics; D014748:Vinca Alkaloids / Q000493:pharmacokinetics
D018943:Anthracyclines; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D014748:Vinca Alkaloids; D004317:Doxorubicin; D003520:Cyclophosphamide; D011034:Podophyllotoxin; D017239:Paclitaxel