PubMed · 2005 · 94 citations · 27 references
PharmacyOncologyPharmacologyCancer PharmacologyChemotherapyPharmacokinetics Of Anticancer AgentsChemotherapy Dosing SafetyChemotherapy Drug AdministrationChemotherapy Toxicity ManagementCytotoxic ChemotherapyPharmacokinetics In Liver DiseaseToxicity ManagementChemotherapy Administration SafetyChemotherapy-associated HepatotoxicityChemotherapy-induced HepatotoxicityContinuous Infusion DosingHepatic Function-based DosingOncology Chemotherapy DosingPharmacokinetics Of Cytotoxic ChemotherapyTherapeutic Index Narrow Drugs
Advanced cancer patients with liver dysfunction face dosing challenges because most chemotherapeutic agents are hepatically metabolized, have narrow therapeutic indices, and safety data are limited, leaving guidelines largely empirical. This review examines how to dose cancer chemotherapy in patients with liver dysfunction. The review finds that agents such as continuous‑infusion fluorouracil, capecitabine, mechlorethamine, cyclophosphamide, topotecan, and oxaliplatin are relatively well tolerated, whereas taxanes, vinca alkaloids, irinotecan, and anthracyclines may produce unacceptable toxicity in patients with poor hepatic function.
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.
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Five Years Clinical Experience with 5-Fluorouracil
Fred J. Ansfield · JAMA · 1962 · 218 citations
Medicine, Oncology, Pharmacology +14