Journal
CANCER CHEMOTHERAPY AND PHARMACOLOGY
Volume 84, Issue 1, Pages 163-173Publisher
SPRINGER
DOI: 10.1007/s00280-019-03856-9
Keywords
Acute myeloid leukemia; Acute lymphoblastic leukemia; Cardiac repolarization; Pharmacokinetics; Pharmacodynamics
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Funding
- Jazz Pharmaceuticals, Inc.
- Celator Pharmaceuticals, Inc., a subsidiary of Jazz Pharmaceuticals, Inc.
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PurposeDaunorubicin 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.MethodsTwenty-six adults with acute leukemia were treated with CPX-351 for 1-2 induction cycles and4 consolidation cycles. The primary endpoint was mean change in QTcF from baseline.ResultsMean QTcF changes were<10ms 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>30h. Thirteen (50%) patients achieved remission. The most common adverse events were febrile neutropenia, fatigue, and nausea.ConclusionsThe 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 registrationClinicaltrials.gov identifier: NCT02238925.
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