An open-label, exploratory, limited dose escalation study to evaluate the pharmacokinetics, safety and tolerability of gemcitabine hydrochloride oral formulation in subjects with malignant tumors.

e13537 Background: This open-label, phase 0, dose-escalation study of 3 successive cohorts was conducted to determine and characterize the plasma PK of D07001-F4, an oral formulation of gemcitabine HCl, in subjects with malignant tumors. Oral tolerability and safety were also assessed. Methods: Patients aged ≧18 yrs with PS 0–2 were eligible. D07001-F4 doses of either 2, 5, or 10 mg PO were administered once on Day 1 with 7 days of safety follow-up. Plasma and peripheral blood mononuclear cell (PBMC) samples were obtained for analysis of concentrations of, respectively, gemcitabine (dFdC) and 2’,2’-difluorodeoxyuridine (dFdU); and gemcitabine triphosphate (dFdCTP). Results: 3 subjects each (median 65 years [range 45 - 74]) were assigned to 3 dose escalation cohorts (2, 5, 10 mg). The PK parameter of Cmax was determined for dFdC and dFdCTP; Cmaxand AUC were found to be dose proportional, and the half-life was greater than 100 hours for dFdU. 24 adverse events were reported for 7 out of 9 subjects (78%). On...