RRC ID 56687
Author Adiwijaya BS, Kim J, Lang I, Csõszi T, Cubillo A, Chen JS, Wong M, Park JO, Kim JS, Rau KM, Melichar B, Gallego JB, Fitzgerald J, Belanger B, Molnar I, Ma WW.
Title Population Pharmacokinetics of Liposomal Irinotecan in Patients With Cancer.
Journal Clin Pharmacol Ther
Abstract Nanoliposomal irinotecan (nal-IRI) is a liposomal formulation of irinotecan with a longer half-life (t1/2 ), higher plasma total irinotecan (tIRI), and lower SN-38 maximum concentration (Cmax ) compared with nonliposomal irinotecan. Population pharmacokinetic (PK) analysis of nal-IRI was performed for tIRI and total SN-38 (tSN38) using patient samples from six studies. PK-safety association was evaluated for neutropenia and diarrhea in 353 patients. PK-efficacy association was evaluated from a phase III study in pancreatic cancer NAPOLI1. Efficacy was associated with longer duration of unencapsulated SN-38 (uSN38) above a threshold and higher Cavg of tIRI, tSN38, and uSN38. Neutropenia was associated with uSN38 Cmax and diarrhea with tIRI Cmax . Baseline predictive factors were race, body surface area, and bilirubin. Analysis identified PK factors associated with efficacy, safety, and predictive baseline factors. The results support the benefit of nal-IRI dose of 70 mg/m2 (free-base; equivalent to 80 mg/m2 salt base) Q2W over 100 mg/m2 Q3W.
Volume 102(6)
Pages 997-1005
Published 2017-12-1
DOI 10.1002/cpt.720
PMID 28445610
PMC PMC5697569
MeSH Adult Aged Camptothecin / adverse effects Camptothecin / analogs & derivatives* Camptothecin / blood Camptothecin / pharmacokinetics Clinical Trials as Topic Diarrhea / chemically induced Female Humans Irinotecan Liposomes / adverse effects* Liposomes / blood Liposomes / pharmacokinetics* Male Middle Aged Neoplasms / blood Neoplasms / drug therapy Neoplasms / metabolism* Neutropenia / chemically induced
IF 6.336
Times Cited 11
Human and Animal Cells KP4(RCB1005)