Simultaneous Modeling of Biomarker and Toxicity Response Predicted Optimal Regimen of Guadecitabine (SGI-110) in Myeloid Malignancies.

ABSTRACT: Guadecitabine (SGI-110) is a novel next-generation hypomethylating agent (HMA) administered as s.c. injection with extended decitabine exposure. Dose/exposure-response analyses of longitudinal measures of long interspersed nucleotide element-1 (LINE-1) methylation and absolute neutrophil counts (ANC) pooled from 79 and 369 patients in 2 phase I/II trials, respectively, were performed to assist, through modeling and simulation, the selection of dosing regimens for phase III. Simulation of ANC predicted a decrease after a 5-day regimen of 60 mg/m² with partial recovery before the next cycle, whereas the nadir of 90 mg/m² on the same schedule was below 100/µl. ANC following a 60 mg/m² 10-day regimen was predicted to be suppressed below 100/µl as long as treatm

SUBMITTER: Xu C 

PROVIDER: S-EPMC5658282 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature