Doxorubicin Pharmacokinetics and Toxicity in Patients with Aggressive Lymphoma and Hepatic Impairment.

Aggressive lymphomas are curable with doxorubicin-based chemotherapy. In patients presenting with elevated serum bilirubin, doxorubicin is commonly dose-reduced or delayed based on limited pharmacokinetic data. We evaluated plasma pharmacokinetics of doxorubicin and its metabolite doxorubicinol, and toxicity in 59 patients with normal bilirubin and 10 with elevated bilirubin levels. Patients received full-dose EPOCH +/-rituximab. Median (range) age was 51 (18-75) years. Patients with elevated bilirubin had higher IPI and poorer performance status. Although median doxorubicin clearance was lower, and median plasma doxorubicin and doxorubicinol concentrations were higher in patients with elevated bilirubin, values were within the concentration range observed in patients with normal bilirubin. Rates of febrile neutropenia were similar between groups, but there was greater grade 4 neutropenia and thrombocytopenia during the first but not subsequent treatment cycles in patients with elevated bilirubin. More grade 3/4 gastrointestinal and neurotoxicity occurred in patients with elevated bilirubin during the first but not subsequent cycles. Although toxicity was greater on cycle 1, the adverse effects were managed safely. These results show that empiric dose reductions of continuous infusion doxorubicin may not be necessary in patients with elevated bilirubin.