Simultaneous Modeling of Biomarker and Toxicity Response Predicted Optimal Regimen of Guadecitabine (SGI-110) in Myeloid Malignancies.
CPT Pharmacometrics Syst Pharmacol
; 6(10): 712-718, 2017 10.
Article
em En
| MEDLINE
| ID: mdl-28960845
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 treatment continued without recovery. The developed models provided useful tools to assist simultaneous evaluation of the relative dynamics of the two effects (DNA demethylation and the effect on ANC).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Azacitidina
/
Leucemia
/
Elementos Nucleotídeos Longos e Dispersos
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
CPT Pharmacometrics Syst Pharmacol
Ano de publicação:
2017
Tipo de documento:
Article