Difference between revisions of "Vosaroxin (SNS-595)"
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==General information== | ==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.<ref>[http://www.sunesis.com/products-in-development/product/Vosaroxin.php Vosaroxin information at Sunesis Pharmaceuticals]</ref><ref>[http://www.sunesis.com/products-in-development/products-in-development/moa/Vosaroxin.php Vosaroxin mechanism of action (Sunesis)]</ref><ref>[http://www.sunesis.com/patients_and_caregivers/clinical_trials/Vosaroxin.php Vosaroxin clinical trials (Sunesis)]</ref> | 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.<ref>[http://www.sunesis.com/products-in-development/product/Vosaroxin.php Vosaroxin information at Sunesis Pharmaceuticals]</ref><ref>[http://www.sunesis.com/products-in-development/products-in-development/moa/Vosaroxin.php Vosaroxin mechanism of action (Sunesis)]</ref><ref>[http://www.sunesis.com/patients_and_caregivers/clinical_trials/Vosaroxin.php Vosaroxin clinical trials (Sunesis)]</ref> | ||
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<br>Extravasation: no information | <br>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. | + | 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 [http://www.thomsonhc.com/home/dispatch Micromedex], [http://online.lexi.com/ Lexicomp], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the package insert. |
| − | == | + | ==Preliminary data== |
| − | + | ===[[Acute myeloid leukemia]]=== | |
| − | + | # 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. [https://pubmed.ncbi.nlm.nih.gov/25381131/ PubMed] | |
| − | + | # 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. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354261/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25403830/ PubMed] | |
| − | + | # 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. [https://pubmed.ncbi.nlm.nih.gov/25805811/ PubMed] | |
| + | # '''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. [https://doi.org/10.1016/S1470-2045(15)00201-6 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26234174/ PubMed] | ||
| + | ## '''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. [http://www.haematologica.org/content/103/11/e514.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278965/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29794146/ PubMed] | ||
==Patient drug information== | ==Patient drug information== | ||
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==Also known as== | ==Also known as== | ||
| − | SNS-595 | + | *'''Code name:''' SNS-595 |
| + | *'''Generic name:''' voreloxin | ||
==References== | ==References== | ||
<references/> | <references/> | ||
| − | [[Category: | + | [[Category:Drugs]] |
| − | [[Category: | + | [[Category:Intravenous medications]] |
| − | [[Category: | + | |
| + | [[Category:Topoisomerase II inhibitors]] | ||
| + | |||
| + | [[Category:Acute myeloid leukemia medications (investigational)]] | ||
| − | [[Category: | + | [[Category:Investigational drugs]] |
Latest revision as of 00:17, 23 September 2023
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.[1][2][3]
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, UpToDate (courtesy of Lexicomp), or the package insert.
Preliminary data
Acute myeloid leukemia
- 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. PubMed
- 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 PubMed
- 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. PubMed
- 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 contains dosing details in abstract PubMed
- 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 PubMed
Patient drug information
No information available.
Also known as
- Code name: SNS-595
- Generic name: voreloxin