Two phase I, pharmacokinetic, and pharmacodynamic studies of DFP-10917, a novel nucleoside analog with 14-day and 7-day continuous infusion schedules.

ABSTRACT: Purpose DFP-10917 is a novel deoxycytidine analog with a unique mechanism of action. Brief exposure to high concentrations of DFP-10917 inhibits DNA polymerase resulting in S-phase arrest, while prolonged exposure to DFP-10917 at low concentration causes DNA fragmentation, G2/M-phase arrest, and apoptosis. DFP-10917 demonstrated activity in tumor xenografts resistant to other deoxycytidine analogs. Experimental design Two phase I studies assessed the safety, pharmacokinetic, pharmacodynamic and preliminary efficacy of DFP-10917. Patients with refractory solid tumors received DFP-10917 continuous infusion 14-day on/7-day off and 7-day on/7-day off. Enrollment required age > 18 years, ECOG Performance Status 0-2 and adequate organ function. Results 29 patients were dosed in both studies. In

SUBMITTER: Sankhala K 

PROVIDER: S-EPMC6521838 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature