Vosaroxin (SNS-595)

==General information==
Class/mechanism: Anticancer quinolone derivative (AQD). Vosaroxin intercalates DNA and inhibits topoisomerase II activity, which results in site-specific double-strand DNA breaks, G2 arrest in the cell cycle, and apoptosis. It is hypothesized that it may not be vulnerable to certain mechanisms of resistance since it is not a P-glycoprotein (P-gp) substrate. The vosaroxin naphthyridine core is believed to be less chemically promiscuous and to generate fewer reactive oxygen species (ROS), which could decrease the risk of cardiotoxicity. Its activity is independent of the p53 family.Vosaroxin information at Sunesis PharmaceuticalsVosaroxin mechanism of action (Sunesis)Vosaroxin clinical trials (Sunesis)
Route: IV
Extravasation: no information
For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, or the package insert.
==Preliminary data==
Note: This is not meant to be an exhaustive list of preliminary results. References included in this section include non-randomized studies published in high-profile journals (e.g., NEJM) and experimental arms of phase 3 RCTs. Inclusion here is not an indication of impending regulatory approval, although many of these drugs do end up receiving approval by a regulatory authority.
===Acute myeloid leukemia===
# SPO-0012: Lancet JE, Roboz GJ, Cripe LD, Michelson GC, Fox JA, Leavitt RD, Chen T, Hawtin R, Craig AR, Ravandi F, Maris MB, Stuart RK, Karp JE. A phase 1b/2 study of combination vosaroxin and cytarabine in patients with relapsed or refractory acute myeloid leukemia. Haematologica. 2015 Feb;100(2):231-7. Epub 2014 Nov 7. link to original article link to PMC article EuroPMC NCT00541866
# Stuart RK, Cripe LD, Maris MB, Cooper MA, Stone RM, Dakhil SR, Turturro F, Stock W, Mason J, Shami PJ, Strickland SA, Costa LJ, Borthakur G, Michelson GC, Fox JA, Leavitt RD, Ravandi F. REVEAL-1, a phase 2 dose regimen optimization study of vosaroxin in older poor-risk patients with previously untreated acute myeloid leukaemia. Br J Haematol. 2015 Mar;168(6):796-805. Epub 2014 Nov 17. link to PMC article EuroPMC
# Dennis M, Russell N, Hills RK, Hemmaway C, Panoskaltsis N, McMullin MF, Kjeldsen L, Dignum H, Thomas IF, Clark RE, Milligan D, Burnett AK. Vosaroxin and vosaroxin plus low-dose Ara-C (LDAC) vs low-dose Ara-C alone in older patients with acute myeloid leukemia. Blood. 2015 May 7;125(19):2923-32. Epub 2015 Mar 24. link to original article link to PMC article EuroPMC
# VALOR: Ravandi F, Ritchie EK, Sayar H, Lancet JE, Craig MD, Vey N, Strickland SA, Schiller GJ, Jabbour E, Erba HP, Pigneux A, Horst HA, Recher C, Klimek VM, Cortes J, Roboz GJ, Odenike O, Thomas X, Havelange V, Maertens J, Derigs HG, Heuser M, Damon L, Powell BL, Gaidano G, Carella AM, Wei A, Hogge D, Craig AR, Fox JA, Ward R, Smith JA, Acton G, Mehta C, Stuart RK, Kantarjian HM. Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study. Lancet Oncol. 2015 Sep;16(9):1025-36. Epub 2015 Jul 30. link to original article dosing details in abstract have been reviewed by our editors link to PMC article EuroPMC NCT01191801
## Subgroup analysis: Ravandi F, Ritchie EK, Sayar H, Lancet JE, Craig MD, Vey N, Strickland SA, Schiller GJ, Jabbour E, Pigneux A, Horst HA, Récher C, Klimek VM, Cortes JE, Carella AM, Egyed M, Krug U, Fox JA, Craig AR, Ward R, Smith JA, Acton G, Kantarjian HM, Stuart RK. Phase 3 results for vosaroxin/cytarabine in the subset of patients ≥60 years old with refractory/early relapsed acute myeloid leukemia. Haematologica. 2018 Nov;103(11):e514-e518. Epub 2018 May 24. link to original article link to PMC article EuroPMC
==Patient drug information==
No information available.
==Also known as==
*Code name: SNS-595
*Generic name: voreloxin
==References==
Category:Drugs
Category:Intravenous medications
Category:Topoisomerase II inhibitors
Category:Acute myeloid leukemia medications (investigational)
Category:Investigational drugs