Chemotherapy dosing in the setting of liver dysfunction

Advanced cancer in the setting of liver dysfunction poses a dilemma for physicians, as many cancer chemotherapeutic agents undergo hepatic metabolism. Most cytotoxic drugs have a narrow therapeutic index, and the administration of chemotherapy to patients with liver impairment results in complicated safety issues. We present a concise review of cancer chemotherapy dosing in the setting of liver dysfunction. Although caution in treating all patients with hepatic failure is essential, the use of certain agents provokes greater concern than others. Continuous-infusion fluorouracil, capecitabine (Xeloda), mechlorethamine (Mustargen), cyclophosphamide, topotecan (Hycamtin), and oxaliplatin (Eloxatin) appear to be relatively well tolerated. On the contrary, taxanes, vinca alkaloids, irinotecan (Camptosar), and anthracyclines may cause unacceptable toxicity if administered to patients with poor hepatic function. For many anticancer agents, the paucity of data prohibits formal dosing recommendations, and most guidelines remain empiric.