Skip to main content
main-content

16.05.2019 | Original Article Open Access

A phase 2 study to assess the pharmacokinetics and pharmacodynamics of CPX-351 and its effects on cardiac repolarization in patients with acute leukemias

Zeitschrift:
Cancer Chemotherapy and Pharmacology
Autoren:
Tara L. Lin, Laura F. Newell, Robert K. Stuart, Laura C. Michaelis, Eric Rubenstein, Helen S. Pentikis, Timothy Callahan, Donna Alvarez, Barry D. Liboiron, Lawrence D. Mayer, Qi Wang, Kamalika Banerjee, Arthur C. Louie
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00280-019-03856-9) contains supplementary material, which is available to authorized users.
Kamalika Banerjee and Arthur C. Louie were employees of Jazz Pharmaceuticals, Inc., at the time this study and subsequent analyses were performed.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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.

Unsere Produktempfehlungen

e.Med Interdisziplinär

Kombi-Abonnement

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf SpringerMedizin.de. Zusätzlich können Sie eine Zeitschrift Ihrer Wahl in gedruckter Form beziehen – ohne Aufpreis.

e.Med Innere Medizin

Kombi-Abonnement

Mit e.Med Innere Medizin erhalten Sie Zugang zu CME-Fortbildungen des Fachgebietes Innere Medizin, den Premium-Inhalten der internistischen Fachzeitschriften, inklusive einer gedruckten internistischen Zeitschrift Ihrer Wahl.

e.Med Onkologie

Kombi-Abonnement

Mit e.Med Onkologie erhalten Sie Zugang zu CME-Fortbildungen des Fachgebietes Onkologie, den Premium-Inhalten der onkologischen Fachzeitschriften, inklusive einer gedruckten onkologischen Zeitschrift Ihrer Wahl.

Zusatzmaterial
Supplementary file1 (DOCX 36 kb)
280_2019_3856_MOESM1_ESM.docx
Literatur
Über diesen Artikel

Neu im Fachgebiet Onkologie

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Onkologie und bleiben Sie gut informiert – ganz bequem per eMail.

Bildnachweise