TY - JOUR
T1 - Vosaroxin
T2 - innovative anticancer quinolone for the treatment of acute myelogenous leukemia
AU - Marx, Kayleigh R.
AU - Kantarjian, Hagop
AU - Ravandi, Farhad
N1 - Publisher Copyright:
© 2016 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2016/8/2
Y1 - 2016/8/2
N2 - Introduction: A first-in-class anticancer quinolone derivative with topoisomerase II activity, mechanistically, vosaroxin is similar to the anthracycline class. However, vosaroxin displays advantageous pharmacokinetic properties such as minimal metabolism, a lack of free radical production, is not a substrate for the P glycoprotein efflux pump, and can exert its antineoplastic activity independently of P53 function. Vosaroxin has shown encouraging results when combined with cytarabine in older patients with relapsed or refractory acute myeloid leukemia (AML) while balancing early toxicity and mortality, making it a compelling novel therapy for acute myelogenous leukemia. Areas covered: Herein, we review the clinical data from published and internationally presented clinical trials utilizing vosaroxin for AML in the elderly, and relapsed and refractory population. Pivotal trials reviewed include the multicenter, phase II, REVEAL-1 study of single-agent vosaroxin in untreated elderly patients and the multicenter, phase III, VALOR study of vosaroxin in combination with intermediate dose cytarabine for patients with relapsed or refractory AML. Expert opinion: Outcomes for older adults with AML, and for patients with relapsed or refractory disease are persistently poor. Improvement in outcomes in the elderly population highlight the utility of this agent in a difficult to treat, often more resistant and intolerant to therapy, group of patients. The expected and observed lack of cardiotoxicity makes this drug particularly suitable for the older population, especially those that may have received prior anthracycline based therapy.
AB - Introduction: A first-in-class anticancer quinolone derivative with topoisomerase II activity, mechanistically, vosaroxin is similar to the anthracycline class. However, vosaroxin displays advantageous pharmacokinetic properties such as minimal metabolism, a lack of free radical production, is not a substrate for the P glycoprotein efflux pump, and can exert its antineoplastic activity independently of P53 function. Vosaroxin has shown encouraging results when combined with cytarabine in older patients with relapsed or refractory acute myeloid leukemia (AML) while balancing early toxicity and mortality, making it a compelling novel therapy for acute myelogenous leukemia. Areas covered: Herein, we review the clinical data from published and internationally presented clinical trials utilizing vosaroxin for AML in the elderly, and relapsed and refractory population. Pivotal trials reviewed include the multicenter, phase II, REVEAL-1 study of single-agent vosaroxin in untreated elderly patients and the multicenter, phase III, VALOR study of vosaroxin in combination with intermediate dose cytarabine for patients with relapsed or refractory AML. Expert opinion: Outcomes for older adults with AML, and for patients with relapsed or refractory disease are persistently poor. Improvement in outcomes in the elderly population highlight the utility of this agent in a difficult to treat, often more resistant and intolerant to therapy, group of patients. The expected and observed lack of cardiotoxicity makes this drug particularly suitable for the older population, especially those that may have received prior anthracycline based therapy.
KW - AG-7352
KW - Acute myelogenous leukemia
KW - SNS-595
KW - elderly
KW - voreloxin
KW - vosaroxin
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U2 - 10.1080/21678707.2016.1194753
DO - 10.1080/21678707.2016.1194753
M3 - Article
AN - SCOPUS:84976273872
SN - 2167-8707
VL - 4
SP - 885
EP - 892
JO - Expert Opinion on Orphan Drugs
JF - Expert Opinion on Orphan Drugs
IS - 8
ER -