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Acute myeloid leukemia (AML) represents a disease with a very poor outcome and remains an area of significant unmet need necessitating novel therapeutic strategies. Among novel therapeutic agents, vosaroxin is a first-in-class anticancer quinolone derivative that targets topoisomerase II and induces site-selective double-strand breaks in DNA, leading to tumor cell apoptosis. Areas covered: Herein, the authors provide a comprehensive review of the preclinical development of vosaroxin. This includes coverage of vosaroxin's mechanism of action in addition to its pharmacology and of the main studies reported over the past few years with vosaroxin when used to treat adult AML. Expert opinion: Given that vosaroxin is associated with fewer potential side effects, it may be of benefit to elderly patients with relapsed/refractory AML and to those with additional comorbidities who have previously received an anthracycline and cytarabine combination. Furthermore, vosaroxin also was seen to be active in multidrug-resistant preclinical models. However, further studies have to be performed to better evaluate its place in the armamentarium against AML.

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...

The outcomes of patients with relapsed or refractory acute myeloid leukemia (AML) are dismal, and effective treatment options in this patient population are therefore desperately needed. Vosaroxin is a first-in-class anticancer quinolone derivative that has shown promising activity in patients with relapsed or refractory AML.Studies in relapsed/refractory AML, including a large randomized phase III trial, have shown improved response rates when vosaroxin was combined with cytarabine, which translated to prolonged survival in certain subsets of patients, including older patients. Given the encouraging results of vosaroxin in the relapsed/refractory setting, several studies are also evaluating vosaroxin in older patients with untreated AML who are not candidates for intensive chemotherapy. The results from clinical trials evaluating vosaroxin in both treatment naïve and relapsed/refractory AML will be reviewed. Expert Commentary: Vosaroxin has shown significant promise in the management of AML, especially in older patients with relapsed/refractory disease. As vosaroxin has been associated with increased toxicity in some studies, appropriate dosing and patient selection will be crucial to determine the future role of vosaroxin in AML.

Despite significant advances in diagnosis and supportive care, the majority of patients diagnosed with acute myeloid leukemia (AML) ultimately die of their disease. Standard intensive induction treatment continues to comprise cytarabine and a topoisomerase II (topo II) poison, usually an anthracycline. Vosaroxin , a novel first-in-class quinolone derivative has been developed for use in the treatment of AML as a new-generation topo II inhibitor. It has shown promising activity as a monotherapy and also in combination with intermediate dose cytarabine (IDAC) in relapsed and refractory patient cohorts with minimal toxicity and good tolerability.The authors discuss the mechanism of action of vosaroxin, the pharmacokinetics, safety and tolerability, preclinical and clinical trial results available as well as areas of ongoing research.Vosaroxin has shown efficacy as a novel cytotoxic agent, and despite a similar mechanism of action has significant advantages over anthracyclines. It evades common resistance pathways of p53 and P-glycoprotein (P- gp) and does not appear to generate significant reactive oxygen species (ROS) associated with these agents. Should future investigation confirm its efficacy and advantageous safety profile, vosaroxin could potentially replace older generation topoisomerase poisons in the treatment of AML and other malignant conditions.