Dosage Adjustment and Pharmacokinetic Profile of Irinotecan in Cancer Patients With Hepatic Dysfunction

PURPOSE: To determine the recommended dose (RD) and the pharmacokinetic profile of irinotecan and its metabolites in cancer patients with hyperbilirubinemia. PATIENTS AND METHODS: Patients were assigned to four treatment groups according to their baseline total bilirubin level. Patients in group I (bilirubin within normal range) and group II (bilirubin 1.0 to 1.5 times upper limit of normal [ULN]) received a dose of 350 mg/m2 every 3 weeks. Patients in groups III (bilirubin 1.51 to 3.0 times ULN) and IV (bilirubin > 3.1 times ULN) received starting doses of 175 and 100 mg/m2, respectively. RDs were defined according to the dose-limiting toxicity (DLT) experienced at cycle 1. RESULTS: Thirty-three patients including 21 gastrointestinal cancers were included. Grade 4 febrile neutropenia and diarrhea were common DLTs in patients with hyperbilirubinemia. At a dose of irinotecan 350 mg/m2, DLTs were observed in two of seven and one of five patients in groups I and II, respectively. In group III, escalated dose...