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.
| Original language | English (US) |
|---|---|
| Journal | Cancer Chemotherapy and Pharmacology |
| DOIs | |
| State | Published - Jan 1 2019 |
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Keywords
- Acute lymphoblastic leukemia
- Acute myeloid leukemia
- Cardiac repolarization
- Pharmacodynamics
- Pharmacokinetics
ASJC Scopus subject areas
- Oncology
- Toxicology
- Pharmacology
- Cancer Research
- Pharmacology (medical)
Cite this
A phase 2 study to assess the pharmacokinetics and pharmacodynamics of CPX-351 and its effects on cardiac repolarization in patients with acute leukemias. / Lin, Tara L.; Newell, Laura; Stuart, Robert K.; Michaelis, Laura C.; Rubenstein, Eric; Pentikis, Helen S.; Callahan, Timothy; Alvarez, Donna; Liboiron, Barry D.; Mayer, Lawrence D.; Wang, Qi; Banerjee, Kamalika; Louie, Arthur C.
In: Cancer Chemotherapy and Pharmacology, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A phase 2 study to assess the pharmacokinetics and pharmacodynamics of CPX-351 and its effects on cardiac repolarization in patients with acute leukemias
AU - Lin, Tara L.
AU - Newell, Laura
AU - Stuart, Robert K.
AU - Michaelis, Laura C.
AU - Rubenstein, Eric
AU - Pentikis, Helen S.
AU - Callahan, Timothy
AU - Alvarez, Donna
AU - Liboiron, Barry D.
AU - Mayer, Lawrence D.
AU - Wang, Qi
AU - Banerjee, Kamalika
AU - Louie, Arthur C.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
KW - Acute lymphoblastic leukemia
KW - Acute myeloid leukemia
KW - Cardiac repolarization
KW - Pharmacodynamics
KW - Pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=85066040714&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85066040714&partnerID=8YFLogxK
U2 - 10.1007/s00280-019-03856-9
DO - 10.1007/s00280-019-03856-9
M3 - Article
AN - SCOPUS:85066040714
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
SN - 0344-5704
ER -