Targeting acute myeloid leukemia with TP53-independent vosaroxin.
Vosaroxin is a quinolone compound that intercalates DNA and induces TP53-independent apoptosis, demonstrating activity against acute myeloid leukemia (AML) in Phase I-III trials. Here, we examine vosaroxin's mechanism of action and pharmacology, and we review its use in AML to date, focusing on details of individual clinical trials. Most recently, when combined with cytarabine in a randomized Phase III trial (VALOR), vosaroxin improved outcomes versus cytarabine alone for relapsed/refractory AML in patients older than 60 years and for patients in early relapse. We consider its continued role in the context of a multifaceted strategy against AML, including its current use in clinical trials. Prospective use will define its role in the evolving landscape of AML therapy.
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Christopher B
CB
Benton
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Farhad
F
Ravandi
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D009287:Naphthyridines / Q000494:pharmacology* / Q000627:therapeutic use*; D013844:Thiazoles / Q000494:pharmacology* / Q000627:therapeutic use*; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D009287:Naphthyridines; D013844:Thiazoles; D016159:Tumor Suppressor Protein p53; C485113:vosaroxin
acute myeloid leukemia; antineoplastic agents; intercalating agents; prospective studies; vosaroxin