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Minerva Medica 2020 Sep 21

DOI: 10.23736/S0026-4806.20.07017-2

Copyright © 2020 EDIZIONI MINERVA MEDICA

language: English

CPX-351 - Daunorubicin-cytarabine liposome: a novel formulation to treat patients with newly diagnosed secondary acute myeloid leukemia

Alessandro CAFARO 1, Maria Benedetta GIANNINI 2, Paolo SILIMBANI 1, Delia CANGINI 2, Carla MASINI 1, Andrea GHELLI LUSERNA DI RORÁ 3, Giorgia SIMONETTI 3, Giovanni MARTINELLI 4, Claudio CERCHIONE 2

1 Oncological Pharmacy Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Forlì-Cesena, Italy; 2 Hematology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Forlì-Cesena, Italy; 3 Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Forlì-Cesena, Italy; 4 Scientific Directorate, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Forlì-Cesena, Italy


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In the last few years we assisted to an increasing knowledge about acute myeloid leukemia (AML) pathobiology, however outcomes remain unsatisfactory particularly for adult patients over 60 years old. Not surprisingly several cases of therapy-related AML (tAML) and secondary AML, both characterized by poorer prognosis, are more common in older population. For several decades initial therapy for AML remained unchanged and typically treatment consisted of an anthracycline combined with continuous infusion of cytarabine for 7 days, the so-called “7+3” standard regimen. The efforts made by the researchers to improve this standard schedule, have led to only modest improvement in the response rate (RR) but no change in overall survival (OS), until the recent evolution seen with new target specific mutation therapies. In 2017, a new liposomal-encapsulated formulation with daunorubicin and cytarabine (CPX-351) was approved by the US Food and Drug Administration for the treatment of newly diagnosed tAML or AML with myelodysplasia-related changes (AML-MRCs). Based on the findings that ratiometric delivery may be more effective than administration of either drug at their maximum tolerated dose (MTD), CPX-351 was designed to deliver a fixed 5:1 molar ratio of the two molecules historically used in the standard “7+3” regimen, cytarabine and daunorubicin respectively. CPX-351 did show improvements of overall survival compared to traditional “7+3” in newly diagnosed secondary and therapy-related AML in adults patients. However, questions remain regarding how to select across AML patient subgroups to maximize the clinical benefit. Possible future directions include evaluating CPX-351 dose intensification, combining this liposomal formulation with targeted therapies, and not least important a better understanding about the mechanism of improved responses in tAML and AML-MRC, two entities re 47 cognized to be less chemo-sensitive than other hematologic malignancies. In summary, CPX-351 offers finally something new in the landscape of AML therapy. Herein we will review the rationale behind this new drug product development, the main pharmacological characteristics, and discuss the results of clinical trials that led to its FDA approval at first and by EMA in 2018.


KEY WORDS: Acute myeloid leukemia; Cytarabine; Daunorubicin; CPX-351; Liposome

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