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CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia
PURPOSE: CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic 5:1 drug ratio into leukemia cells to a greater extent than normal bone marrow cells. Prior clinical studies demonstrated a sustained drug ratio and exposure in vivo and prolonged survi...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Clinical Oncology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127025/ https://www.ncbi.nlm.nih.gov/pubmed/30024784 http://dx.doi.org/10.1200/JCO.2017.77.6112 |
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author | Lancet, Jeffrey E. Uy, Geoffrey L. Cortes, Jorge E. Newell, Laura F. Lin, Tara L. Ritchie, Ellen K. Stuart, Robert K. Strickland, Stephen A. Hogge, Donna Solomon, Scott R. Stone, Richard M. Bixby, Dale L. Kolitz, Jonathan E. Schiller, Gary J. Wieduwilt, Matthew J. Ryan, Daniel H. Hoering, Antje Banerjee, Kamalika Chiarella, Michael Louie, Arthur C. Medeiros, Bruno C. |
author_facet | Lancet, Jeffrey E. Uy, Geoffrey L. Cortes, Jorge E. Newell, Laura F. Lin, Tara L. Ritchie, Ellen K. Stuart, Robert K. Strickland, Stephen A. Hogge, Donna Solomon, Scott R. Stone, Richard M. Bixby, Dale L. Kolitz, Jonathan E. Schiller, Gary J. Wieduwilt, Matthew J. Ryan, Daniel H. Hoering, Antje Banerjee, Kamalika Chiarella, Michael Louie, Arthur C. Medeiros, Bruno C. |
author_sort | Lancet, Jeffrey E. |
collection | PubMed |
description | PURPOSE: CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic 5:1 drug ratio into leukemia cells to a greater extent than normal bone marrow cells. Prior clinical studies demonstrated a sustained drug ratio and exposure in vivo and prolonged survival versus standard-of-care cytarabine plus daunorubicin chemotherapy (7+3 regimen) in older patients with newly diagnosed secondary acute myeloid leukemia (sAML). PATIENTS AND METHODS: In this open-label, randomized, phase III trial, 309 patients age 60 to 75 years with newly diagnosed high-risk/sAML received one to two induction cycles of CPX-351 or 7+3 followed by consolidation therapy with a similar regimen. The primary end point was overall survival. RESULTS: CPX-351 significantly improved median overall survival versus 7+3 (9.56 v 5.95 months; hazard ratio, 0.69; 95% CI, 0.52 to 0.90; one-sided P = .003). Overall remission rate was also significantly higher with CPX-351 versus 7+3 (47.7% v 33.3%; two-sided P = .016). Improved outcomes were observed across age-groups and AML subtypes. The incidences of nonhematologic adverse events were comparable between arms, despite a longer treatment phase and prolonged time to neutrophil and platelet count recovery with CPX-351. Early mortality rates with CPX-351 and 7+3 were 5.9% and 10.6% (two-sided P = .149) through day 30 and 13.7% and 21.2% (two-sided P = .097) through day 60. CONCLUSION: CPX-351 treatment is associated with significantly longer survival compared with conventional 7+3 in older adults with newly diagnosed sAML. The safety profile of CPX-351 was similar to that of conventional 7+3 therapy. |
format | Online Article Text |
id | pubmed-6127025 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Society of Clinical Oncology |
record_format | MEDLINE/PubMed |
spelling | pubmed-61270252018-09-11 CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia Lancet, Jeffrey E. Uy, Geoffrey L. Cortes, Jorge E. Newell, Laura F. Lin, Tara L. Ritchie, Ellen K. Stuart, Robert K. Strickland, Stephen A. Hogge, Donna Solomon, Scott R. Stone, Richard M. Bixby, Dale L. Kolitz, Jonathan E. Schiller, Gary J. Wieduwilt, Matthew J. Ryan, Daniel H. Hoering, Antje Banerjee, Kamalika Chiarella, Michael Louie, Arthur C. Medeiros, Bruno C. J Clin Oncol RAPID COMMUNICATION PURPOSE: CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic 5:1 drug ratio into leukemia cells to a greater extent than normal bone marrow cells. Prior clinical studies demonstrated a sustained drug ratio and exposure in vivo and prolonged survival versus standard-of-care cytarabine plus daunorubicin chemotherapy (7+3 regimen) in older patients with newly diagnosed secondary acute myeloid leukemia (sAML). PATIENTS AND METHODS: In this open-label, randomized, phase III trial, 309 patients age 60 to 75 years with newly diagnosed high-risk/sAML received one to two induction cycles of CPX-351 or 7+3 followed by consolidation therapy with a similar regimen. The primary end point was overall survival. RESULTS: CPX-351 significantly improved median overall survival versus 7+3 (9.56 v 5.95 months; hazard ratio, 0.69; 95% CI, 0.52 to 0.90; one-sided P = .003). Overall remission rate was also significantly higher with CPX-351 versus 7+3 (47.7% v 33.3%; two-sided P = .016). Improved outcomes were observed across age-groups and AML subtypes. The incidences of nonhematologic adverse events were comparable between arms, despite a longer treatment phase and prolonged time to neutrophil and platelet count recovery with CPX-351. Early mortality rates with CPX-351 and 7+3 were 5.9% and 10.6% (two-sided P = .149) through day 30 and 13.7% and 21.2% (two-sided P = .097) through day 60. CONCLUSION: CPX-351 treatment is associated with significantly longer survival compared with conventional 7+3 in older adults with newly diagnosed sAML. The safety profile of CPX-351 was similar to that of conventional 7+3 therapy. American Society of Clinical Oncology 2018-09-10 2018-07-19 /pmc/articles/PMC6127025/ /pubmed/30024784 http://dx.doi.org/10.1200/JCO.2017.77.6112 Text en © 2018 by American Society of Clinical Oncology http://creativecommons.org/licenses/by-nc-nd/4.0/ Licensed under the Creative Commons Attribution 4.0 License: http://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | RAPID COMMUNICATION Lancet, Jeffrey E. Uy, Geoffrey L. Cortes, Jorge E. Newell, Laura F. Lin, Tara L. Ritchie, Ellen K. Stuart, Robert K. Strickland, Stephen A. Hogge, Donna Solomon, Scott R. Stone, Richard M. Bixby, Dale L. Kolitz, Jonathan E. Schiller, Gary J. Wieduwilt, Matthew J. Ryan, Daniel H. Hoering, Antje Banerjee, Kamalika Chiarella, Michael Louie, Arthur C. Medeiros, Bruno C. CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia |
title | CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia |
title_full | CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia |
title_fullStr | CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia |
title_full_unstemmed | CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia |
title_short | CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia |
title_sort | cpx-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia |
topic | RAPID COMMUNICATION |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127025/ https://www.ncbi.nlm.nih.gov/pubmed/30024784 http://dx.doi.org/10.1200/JCO.2017.77.6112 |
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