Translate this page into:
Drug Review
doi:
10.4103/2278-330X.149950
Novel formulation of cytarabine and daunorubicin: A new hope in AML treatment
1
Department of Medicine, Leukemia/BMT Division, Vancouver General Hospital, Vancouver, British Columbia
*Corresponding author: Dr. Lalit Raut. lalitraut76@yahoo.co.in
MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)
Disclaimer:
This article was originally published by Thieme Medical and Scientific Publishers Pvt. Ltd. and was migrated to Scientific Scholar after the change of Publisher.
This article was originally published by Thieme Medical and Scientific Publishers Pvt. Ltd. and was migrated to Scientific Scholar after the change of Publisher.
Abstract
Abstract
Acute myeloid leukemia (AML) treatment has always been a challenge to the treating physician. Continuous efforts are being made to improve treatment outcomes in AML. CPX-351 is a pharmacologic advancement in this direction. It is a liposomal fixed drug combination of cytarabine and daunorubicin. Early studies indicate that it will play a big role in AML treatment. This is a short review about this drug.
Keywords
References
- Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 1984;22:27-55.
- Mayer LD, Janoff AS. Optimizing combination chemotherapy by controlling drug ratios. Mol Interv 2007;7:216-23.
- Mayer LD, Harasym TO, Tardi PG, Harasym NL, Shew CR, Johnstone SA, et al. Ratiometric dosing of anticancer drug combinations: Controlling drug ratios after systemic administration regulates therapeutic activity in tumor-bearing mice. Mol Cancer Ther 2006;5:1854-63.
- Tardi P, Johnstone S, Harasym N, Xie S, Harasym T, Zisman N, et al. In vivo maintenance of synergistic cytarabine: Daunorubicin ratios greatly enhances therapeutic efficacy. Leuk Res 2009;33:129-39.
- Harasym T, Lim W, Tardi P, Xie S, Fan M, Huang R, et al. Leukemia Cell-Selective Uptake of Cytarabine (Cyt) and Daunorubicin (Daun) Mediated by CPX-351 Liposome Injection in the Bone Marrow Compartment [abstract]. Presented at the 14 th Congress of the European Hematology Association; 2009 June 4-7; Berlin, Germany. Haematologica 2009:94:1-694.
- Feldman E, Lancet J, Kolitz JE, Trang JM, Mayer L, Louie A. Pharmacology of CPX-351: A Nano-scale Liposomal Fixed Molar Ratio Cytarabine-Daunorubicin for Patients with Advanced Leukemia. Presented at the 14 th Congress of the European Hematology Association; 2009 June 4-7; Berlin, Germany. Haematologica 2009;94:1-694.
- Feldman EJ, Lancet JE, Kolitz JE, Ritchie EK, Roboz GJ, List AF, et al. First-in-man study of CPX-351: A liposomal carrier containing cytarabine and daunorubicin in a fixed 5:1 molar ratio for the treatment of relapsed and refractory acute myeloid leukemia. J Clin Oncol 2011;29:979-85.
- Cortes JE, Feldman EJ, Goldberg SL, Rizzieri DA, Paulsen KH, Louie AC, et al. CPX-351: A Randomized Phase 2b Study of CPX-351 v. Intensive Salvage Therapy in 65 Yo First Relapse AML Patients: Initial Efficacy and Safety Report. Presented at the ASH 2011 Annual Meeting; 2011 December 9-13; San Diego, CA. Blood; 2011:118.
- Lancet J, Feldman E, Cortes J, Hogge D, Kovacsovics T, Tallman M et al. Phase II b Randomized Study of CPX-351 vs. Conventional Cytarabine+Daunorubicin in Newly Diagnosed AML Patients Aged 60-75: Safety Report [abstract]. Presented at the ASH 2009 Annual Meeting; 2009 December 9-13; New Orleans, LA. Blood 2009;114.
- Lancet J, Cortes J, Kovacsovics T, Hogge D, Kolitz JE, Tallman MS, et al. CPX-351 versus cytarabine (CYT) and daunorubicin (DNR) therapy in newly diagnosed AML patients age 60-75: Safety and efficacy in secondary AML (sAML) [abstract]. Presented at ASCO 2011 Annual Meeting; 2011 June 3-7; Chicago, IL, USA. J Clin Oncol 2011;29.
- Cortes JE, Feldman EJ, Goldberg SL, Rizzieri DA, Louie AC, Paulsen KH, et al. Phase II B, multicenter, randomised, open-label trial of CPX-351 (cytarabine: daunorubicin) liposome injection versus intensive salvage therapy in adult patients≤65 years old with aml in first relapse following an initial CR>1 month duration (study 205). Available from: http://www.celatorpharma.com/new/files/poster_2011_Cortes%20et%20al%20205%20ASH%202011.pdf [Last accessed on 2014 Feb 10].
- Lancet J, Feldman E, Cortes J, Hogge D, Kovacsovics T, Tallman M et al. CPX-351 Can Induce Remission in AML Immediately After Failed Induction with Cytarabine and Daunorubicin [abstract]. Presented at ASCO 2010 Annual Meeting; 2010 Jun 4-8; Chicago, IL, USA. J Clin Oncol; 2010;28.
- Tardi P, Harasym T, Dos Santos N, Lim W-S, Xie S, Ciofani T, et al. CPX-351, a liposome formulation containing a synergistic 5:1 molar ratio of cytarabine (Cyt) and daunorubicin (Daun), exhibits improved efficacy against human leukemia xenografts when administered at intermediate frequency in consolidation treatment [abstract]. Presented at the AACR 2009 Annual Meeting; 2009 April 18-22; Denver, CO: AACR; 2009.
- Gergis, Usama, Roboz, Gail J, Ritchie, Ellen, et al. A novel sequential treatment utilizing cpx-351 as salvage chemotherapy followed by a reduced intensity conditioning allogeneic stem-cell transplantation for patients with refractory leukemia. Presented at the ASH 2011 Annual Meeting; 2011 December 9-13; San Diego, CA. Blood; 2011:118.
- Feldman E, Lancet J, Kolitz JE, Hogge D, Tallman MS, Goldberg S, et al. Multivariate analysis of factors affecting overall survival, event free survival, and 60-day mortality among AML patients treated with CPX-351 or intensive chemotherapy [abstract]. Presented at the ASCO 2013 Annual Meeting; 2013 May 31-June 4; Chicago. J Clin Oncol 2013;31:15.
- Goldberg S, Cortes J, Feldman EJ, Rizzleri DA, Kantarjian HM, Limor S, et al. Initial salvage therapy in first relapse AML: A phase IIb study of CPX-351 versus investigator′s choice: A subset analysis by prognostic group [abstract]. Presented at the ASCO 2012 Annual Meeting; 2012 June 1-5; Chicago, IL, USA. J Clin Oncol 2012;30:15.
- Lancet JE, Cortes JE, Kovacsovics T, Hogge D, Kolitz JE, Tallman MS, et al. The Impact of Prior Hypomethylating Agent Treatment among Secondary AML Patients Treated with CPX-351 or 7+3 Chemotherapy [abstract]. Presented at the 16 th Congress of the EHA; 2011 June 9-12; London. Haematologica 2011;96:1-773.
- Cortes JE, Feldman EJ, Goldberg SL, Rizzieri DA, Louie AC, Kolitz JE. Significance of Prior HSCT on the Outcome of Salvage Therapy with CPX-351 or Conventional Chemotherapy among First Relapse AML patients [abstract]. Presented at the ASH 2011 Annual Meeting; 2011 December 9-13; San Diego, CA. Blood 2011:118.
- Phase III Study of CPX-351 Versus 7+3 in Patients 60-75 Years Old With Untreated High Risk (Secondary) Acute Myeloid Leukemia. Available from: http://clinicaltrials.gov/ct2/show/results/NCT01696084 [Last accessed on 2014 Feb 10].
- Tyner JW, Mayer L, Tardi P, Fletcher LB, Spurgeon SE, Kovacsovics T, et al. Evaluation of cpx-351 anti-leukemic activity against primary patient leukemia cells [abstract]. Presented at the ASH 2010 Annual Meeting; 2010 December 4-7; Orlando, FL. Blood 2010:116.