ORIGINAL REPORTS-Clinical Pharmacology and Pharmacokinetics-Phase I and Pharmacologic Study of Irinotecan Administered as a 96-Hour Infusion Weekly to Adult Cancer Patients

摘要: Purpose We conducted a phase I and pharmacologic study of a weekly 96-hour infusion of irinotecan to determine the maximum-tolerated dose, define the toxicity profile, and characterize the clinical pharmacology of irinotecan and its metabolites. Patients and Methods In 26 adult patients with solid tumors, the duration and dose rate of infusion were escalated in new patients until toxicity was observed. Results In 11 patients who were treated with irinotecan at 12.5 mg/m2/d for 4 days weekly for 2 of 3 weeks, dose-limiting grade 3 diarrhea occurred in three patients and grade 3 thrombocytopenia occurred in two patients. The recommended phase II dose is 10 mg/m2/d for 4 days given weekly for 2 of 3 weeks. At this dose, the steady-state plasma concentration (Css) of total SN-38 (the active metabolite of irinotecan) was 6.42 +- 1.10 nmol/L, and the Css of total irinotecan was 28.60 +- 17.78 nmol/L. No patient …