@article{dcba58dad4a94e73a8fd9b2146ea2f64,
title = "A phase 2 study to assess the pharmacokinetics and pharmacodynamics of CPX-351 and its effects on cardiac repolarization in patients with acute leukemias",
abstract = "Purpose: Daunorubicin can induce left ventricular dysfunction and QT interval prolongation. This study assessed the effects of CPX-351, a liposomal encapsulation of cytarabine and daunorubicin, on cardiac repolarization. Methods: Twenty-six adults with acute leukemia were treated with CPX-351 for 1–2 induction cycles and ≤ 4 consolidation cycles. The primary endpoint was mean change in QTcF from baseline. Results: Mean QTcF changes were < 10 ms at all time points. No clinically meaningful effects on heart rate, QRS interval, PR interval, or QTcB were observed. Estimated mean half-lives for total cytarabine and daunorubicin were > 30 h. Thirteen (50%) patients achieved remission. The most common adverse events were febrile neutropenia, fatigue, and nausea. Conclusions: The cytarabine and daunorubicin in CPX-351 liposomes were metabolized and excreted similarly to conventional formulation; however, plasma pharmacokinetics were altered. CPX-351 did not prolong the QT interval, suggesting that CPX-351 may induce less cardiotoxicity than previously reported for conventional daunorubicin. Trial registration: Clinicaltrials.gov identifier: NCT02238925.",
keywords = "Acute lymphoblastic leukemia, Acute myeloid leukemia, Cardiac repolarization, Pharmacodynamics, Pharmacokinetics",
author = "Lin, {Tara L.} and Newell, {Laura F.} and Stuart, {Robert K.} and Michaelis, {Laura C.} and Eric Rubenstein and Pentikis, {Helen S.} and Timothy Callahan and Donna Alvarez and Liboiron, {Barry D.} and Mayer, {Lawrence D.} and Qi Wang and Kamalika Banerjee and Louie, {Arthur C.}",
note = "Funding Information: Acknowledgements Medical writing and editorial assistance for the preparation of this manuscript were provided by Erica Chevalier-Larsen, PhD, CMPP{\texttrademark}, of SciFluent Communications, under the direction of the authors; this assistance was financially supported by Jazz Pharmaceuticals, Inc. This study was sponsored by Celator Pharmaceuticals, Inc., a subsidiary of Jazz Pharmaceuticals, Inc. Funding Information: board participation for Pfizer. RKS reports honoraria, consulting, and travel support from Sunesis; and institutional research funding from Agios, Astellas, Bayer, Celator/Jazz, Incyte, and Sunesis. LCM reports research funding from Jazz; consulting and advisory board participation for Incyte, TG Therapeutics, Novartis, and Celgene; and stock ownership in Pfizer. ER reports speakers bureau participation for Alex-ion Pharmaceuticals and AstraZeneca; and advisory board participation for Celgene. HSP reports paid consultation for Celator/Jazz. TC reports employment at ERT. DA, BDL, LDM, and QW report employment at and stock ownership in Celator/Jazz. KB and ACL were former employees of Jazz, and ACL reports stock ownership in Celator/Jazz. LFN reports no potential conflicts of interest. Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = jul,
day = "1",
doi = "10.1007/s00280-019-03856-9",
language = "English (US)",
volume = "84",
pages = "163--173",
journal = "Cancer Chemotherapy and Pharmacology",
issn = "0344-5704",
publisher = "Springer Verlag",
number = "1",
}