@article{27b064b9fd1b4f12bdd39ee2f136df61,
title = "Population Pharmacokinetics of Liposomal Irinotecan in Patients With Cancer",
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.",
author = "Adiwijaya, {B. S.} and J. Kim and I. Lang and T. Cs{\~o}szi and A. Cubillo and Chen, {J. S.} and M. Wong and Park, {J. O.} and Kim, {J. S.} and Rau, {K. M.} and B. Melichar and Gallego, {J. B.} and J. Fitzgerald and B. Belanger and I. Molnar and Ma, {W. W.}",
note = "Funding Information: Drs. Adiwijaya, J Kim, Fitzgerald, Belanger, and Molnar are employees of Merrimack Pharmaceuticals. Drs. Lang, Cso€szi, Cubillo, Chen, JS Kim, Rau, and Gallego Plazas report no conflicts of interest. Dr. Wong reports being a member of a Baxalta advisory board. Dr. Park reports receiving honoraria from Celgene, serving as a consultant for Celgene and Agios Pharmaceuticals, Inc., and receiving research funding from Celgene and AstraZeneca. Dr. Melichar reports receiving honoraria for speeches and advisory roles from Lilly, Sanofi, Roche, Novartis, Pfizer, Janssen, Astel-las, BMS, MSD, GSK, Merck, and Amgen. Dr. Ma reports receiving funding for clinical trials and honorarium for advisory boards from Merrimack Pharmaceuticals. Funding Information: The first two authors contributed equally to this work. This study was funded by Merrimack Pharmaceuticals. We thank Li-Tzong Chen, Stephan Klinz, Bart Hendriks, Marc Pipas, Eliel Bayever, and Peter Laivins for contributions to the design and the interpretation of the analysis. Medical writing support (funded by Merrimack Pharmaceuticals) was provided by Beth Kamp. Publisher Copyright: {\textcopyright} 2017 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.",
year = "2017",
month = dec,
doi = "10.1002/cpt.720",
language = "English (US)",
volume = "102",
pages = "997--1005",
journal = "Clinical Pharmacology and Therapeutics",
issn = "0009-9236",
publisher = "Nature Publishing Group",
number = "6",
}