TY - JOUR
T1 - Liposomal-all-trans-retinoic acid in treatment of acute promyelocytic leukemia
AU - Ozpolat, B.
AU - Lopez-Berestein, G.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2002
Y1 - 2002
N2 - Acute promyelocytic leukemia (APL) characterized by the translocation t(15;17) is uniquely sensitive to the differentiation-inducing effects of all-trans-retinoic acid (ATRA). All-trans-retinoic acid therapy induces complete clinical remissions (CRs) in most of patients with APL. However, chronic daily oral administration of ATRA results in accelerated metabolism of ATRA, leading to a progressive decline in plasma drug concentrations. These lower drug levels are associated with relapses and resistance to oral ATRA in patients with APL; thus the use of ATRA as a single agent is precluded. Liposomal ATRA (Lipo-ATRA) was designed to maintain high and stable plasma concentrations and to further improve the outcome of the APL disease by overcoming the development of ATRA resistance. Liposomal ATRA was shown to circumvent accelerated drug metabolism in the liver of rats in an animal model. In a phase I clinical study, intravenous (i.v.) administration of lipo-ATRA was shown to produce a significantly better pharmacokinetic profile than oral ATRA (non-liposomal) and to maintain higher and sustained plasma drug concentrations, with a similar side effects. More importantly, lipo-ATRA as a single agent induces PCR-negative molecular remissions in a high proportion of newly diagnosed patients with APL and maintain remissions up to 15-17 months or longer. In this review, we discuss the pharmacological features of lipo-ATRA and the molecular remissions induced by lipo-ATRA in newly diagnosed patients with APL or patients previously treated with ATRA or chemotherapy, and the possible impact of lipo-ATRA on the outcome of APL.
AB - Acute promyelocytic leukemia (APL) characterized by the translocation t(15;17) is uniquely sensitive to the differentiation-inducing effects of all-trans-retinoic acid (ATRA). All-trans-retinoic acid therapy induces complete clinical remissions (CRs) in most of patients with APL. However, chronic daily oral administration of ATRA results in accelerated metabolism of ATRA, leading to a progressive decline in plasma drug concentrations. These lower drug levels are associated with relapses and resistance to oral ATRA in patients with APL; thus the use of ATRA as a single agent is precluded. Liposomal ATRA (Lipo-ATRA) was designed to maintain high and stable plasma concentrations and to further improve the outcome of the APL disease by overcoming the development of ATRA resistance. Liposomal ATRA was shown to circumvent accelerated drug metabolism in the liver of rats in an animal model. In a phase I clinical study, intravenous (i.v.) administration of lipo-ATRA was shown to produce a significantly better pharmacokinetic profile than oral ATRA (non-liposomal) and to maintain higher and sustained plasma drug concentrations, with a similar side effects. More importantly, lipo-ATRA as a single agent induces PCR-negative molecular remissions in a high proportion of newly diagnosed patients with APL and maintain remissions up to 15-17 months or longer. In this review, we discuss the pharmacological features of lipo-ATRA and the molecular remissions induced by lipo-ATRA in newly diagnosed patients with APL or patients previously treated with ATRA or chemotherapy, and the possible impact of lipo-ATRA on the outcome of APL.
KW - Acute promyelocytic leukemia
KW - All-trans-retinoic acid
KW - Liposome
KW - Resistance
KW - Retinoic acid receptors
KW - Therapy
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U2 - 10.1080/10428190290021678
DO - 10.1080/10428190290021678
M3 - Review article
C2 - 12148903
AN - SCOPUS:0036233835
SN - 1042-8194
VL - 43
SP - 933
EP - 941
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 5
ER -