Difference between revisions of "Panobinostat (Farydak)"

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m (PeterYang moved page Panobinostat (LBH589) to Panobinostat (Farydak))
(FDA approval)
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'''In clinical trials.'''
 
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==General information==
 
==General information==
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Class/mechanism: Pan-histone deacetylase (HDAC) inhibitor, or HDACi.  Inhibition of histone deacetylases results in hyperacetylation of histones and modulates gene expression by creating an open chromatin state that leads to expression of previously silenced genes.  This modulation has been observed to be associated with decreased expression of oncogenes such as Bcr-Abl and HER-2, induction of cell cycle arrest, promotion of apoptosis, and decreased invasion of tumor cells.<ref>[http://www.novartisoncology.com/research-innovation/pipeline/panobinostat.jsp Panobinostat manufacturer's website]</ref><ref>Hasegawa H, Yamada Y, Tsukasaki K, Mori N, Tsuruda K, Sasaki D, Usui T, Osaka A, Atogami S, Ishikawa C, Machijima Y, Sawada S, Hayashi T, Miyazaki Y, Kamihira S. LBH589, a deacetylase inhibitor, induces apoptosis in adult T-cell leukemia/lymphoma cells via activation of a novel RAIDD-caspase-2 pathway. Leukemia. 2011 Apr;25(4):575-87. Epub 2011 Jan 18. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3089964/ link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/21242994 PubMed]</ref><ref>Crisanti MC, Wallace AF, Kapoor V, Vandermeers F, Dowling ML, Pereira LP, Coleman K, Campling BG, Fridlender ZG, Kao GD, Albelda SM. The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cells in vitro and in vivo with particular efficacy for small cell lung cancer. Mol Cancer Ther. 2009 Aug;8(8):2221-31. Epub 2009 Aug 11. [http://mct.aacrjournals.org/content/8/8/2221.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/19671764 PubMed]</ref>
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Class/mechanism: Pan-histone deacetylase (HDAC) inhibitor, or HDACi.  Inhibition of histone deacetylases results in hyperacetylation of histones and modulates gene expression by creating an open chromatin state that leads to expression of previously silenced genes.  This modulation has been observed to be associated with decreased expression of oncogenes such as Bcr-Abl and HER-2, induction of cell cycle arrest, promotion of apoptosis, and decreased invasion of tumor cells.<ref name=insert>[http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdf Panobinostat (Farydak) package insert]</ref><ref>[[Media:Panobinostat.pdf|Panobinostat (Farydak) package insert, locally hosted backup]]</ref><ref>[http://www.novartisoncology.com/ct/pipelineDetails?compound=LBH589&diseaseAcr=MM Novartis's information about panobinostat]</ref><ref>Hasegawa H, Yamada Y, Tsukasaki K, Mori N, Tsuruda K, Sasaki D, Usui T, Osaka A, Atogami S, Ishikawa C, Machijima Y, Sawada S, Hayashi T, Miyazaki Y, Kamihira S. LBH589, a deacetylase inhibitor, induces apoptosis in adult T-cell leukemia/lymphoma cells via activation of a novel RAIDD-caspase-2 pathway. Leukemia. 2011 Apr;25(4):575-87. Epub 2011 Jan 18. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3089964/ link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/21242994 PubMed]</ref><ref>Crisanti MC, Wallace AF, Kapoor V, Vandermeers F, Dowling ML, Pereira LP, Coleman K, Campling BG, Fridlender ZG, Kao GD, Albelda SM. The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cells in vitro and in vivo with particular efficacy for small cell lung cancer. Mol Cancer Ther. 2009 Aug;8(8):2221-31. Epub 2009 Aug 11. [http://mct.aacrjournals.org/content/8/8/2221.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/19671764 PubMed]</ref>
 
<br>Route: PO
 
<br>Route: PO
 
<br>Extravasation: n/a
 
<br>Extravasation: n/a
  
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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 prescribing information.
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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 prescribing information.<ref name="insert"></ref>
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==Diseases for which it is used==
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*[[Multiple myeloma]]
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*[[Waldenström macroglobulinemia]]
  
 
==Clinical trials==
 
==Clinical trials==
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*[http://clinicaltrials.gov/ct2/show/NCT01242774 Safety & Efficacy Study of Oral Panobinostat (LBH589) With Chemotherapy in Patients < 65 Years Old With Acute Myeloid Leukemia (AML)]
 
*[http://clinicaltrials.gov/ct2/show/NCT01242774 Safety & Efficacy Study of Oral Panobinostat (LBH589) With Chemotherapy in Patients < 65 Years Old With Acute Myeloid Leukemia (AML)]
  
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==Preliminary data==
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==Patient drug information==
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*[http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205353s000lbl.pdf Panobinostat (Farydak) package insert]<ref name=insert></ref>
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===[[Multiple myeloma]]===
 
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====Bortezomib, Dexamethasone & Panobinostat====
 
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=====Regimen #1, San-Miguel et al. 2014 (PANORAMA1)=====
 
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<span
 
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style="background:#00CD00;
 
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padding:3px 6px 3px 6px;
 
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border-color:black;
 
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border-width:2px;
 
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border-style:solid;">Phase III</span>
 
  
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*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
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==History of changes in FDA indication==
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*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
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*2/23/2015: [http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm435296.htm FDA accelerated approval] "for the treatment of patients with multiple myeloma who have received at least 2 prior regimens, including bortezomib and an immunomodulatory agent."
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*[[Panobinostat (LBH589)]] 20mg PO once per day on days 1, 3, 5, 8, 10, 12
 
  
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'''21-day cycles'''
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==Also known as==
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LBH589
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=====Regimen #2, Richardson et al. 2013 (PANORAMA 2)=====
 
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<span
 
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style="background:#EEEE00;
 
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padding:3px 6px 3px 6px;
 
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border-color:black;
 
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border-width:2px;
 
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border-style:solid;">Phase II</span>
 
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======Phase 1======
 
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*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV twice per week
 
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*[[Dexamethasone (Decadron)]] 20 mg PO four times per week (day of and day after bortezomib)
 
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*[[Panobinostat (LBH589)]] 20mg PO three times per week
 
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'''2-weeks on, 1-week off x 8 cycles'''
 
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======Phase 2======
 
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*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per week on weeks 1, 2, 4, 5
 
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*[[Dexamethasone (Decadron)]] 20 mg PO twice per week on weeks 1, 2, 4, 5 (day of and day after bortezomib)
 
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*[[Panobinostat (LBH589)]] 20mg PO three times per week on weeks 1, 2, 4, 5
 
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'''6-week cycles until progression, death, or excess toxicity'''
 
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=====References=====
 
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# Richardson PG, Schlossman RL, Alsina M, Weber DM, Coutre SE, Gasparetto C, Mukhopadhyay S, Ondovik MS, Khan M, Paley CS, Lonial S. PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma. Blood. 2013 Oct 3;122(14):2331-7. Epub 2013 Aug 15. [http://bloodjournal.hematologylibrary.org/content/122/14/2331.full link to original article] '''Contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23950178 PubMed]
 
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# San-Miguel JF, Hungria VT, Yoon SS, Beksac M, Dimopoulos MA, Elghandour A, Jedrzejczak WW, Günther A, Nakorn TN, Siritanaratkul N, Corradini P, Chuncharunee S, Lee JJ, Schlossman RL, Shelekhova T, Yong K, Tan D, Numbenjapon T, Cavenagh JD, Hou J, LeBlanc R, Nahi H, Qiu L, Salwender H, Pulini S, Moreau P, Warzocha K, White D, Bladé J, Chen W, de la Rubia J, Gimsing P, Lonial S, Kaufman JL, Ocio EM, Veskovski L, Sohn SK, Wang MC, Lee JH, Einsele H, Sopala M, Corrado C, Bengoudifa BR, Binlich F, Richardson PG. Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1195-206. Epub 2014 Sep 18. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70440-1/fulltext link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/25242045 PubMed]
 
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===[[Waldenström macroglobulinemia]]===
 
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====Panobinostat====
 
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=====Regimen, Ghobrial et al. 2013=====
 
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<span
 
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style="background:#EEEE00;
 
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padding:3px 6px 3px 6px;
 
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border-color:black;
 
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border-width:2px;
 
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border-style:solid;">Phase II</span>
 
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*[[Panobinostat (LBH589)]] 30 mg PO 3 days per week (Mondays, Wednesdays, and Fridays)
 
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'''28-day cycles, given until progression of disease'''
 
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=====References=====
 
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# Ghobrial IM, Campigotto F, Murphy TJ, Boswell EN, Banwait R, Azab F, Chuma S, Kunsman J, Donovan A, Masood F, Warren D, Rodig S, Anderson KC, Richardson PG, Weller E, Matous J. Results of a phase 2 trial of the single-agent histone deacetylase inhibitor panobinostat in patients with relapsed/refractory Waldenstrom macroglobulinemia. Blood. 2013 Feb 21;121(8):1296-303. Epub 2013 Jan 3. [http://bloodjournal.hematologylibrary.org/content/121/8/1296.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23287861 PubMed]
 
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==Patient drug information==
 
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No information available.
 
  
 
==References==
 
==References==
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[[Category:Waldenström macroglobulinemia medications]]
 
[[Category:Waldenström macroglobulinemia medications]]
  
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[[Category:Investigational]]
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[[Category:Drugs FDA approved in 2015]]

Revision as of 01:36, 24 February 2015

General information

Class/mechanism: Pan-histone deacetylase (HDAC) inhibitor, or HDACi. Inhibition of histone deacetylases results in hyperacetylation of histones and modulates gene expression by creating an open chromatin state that leads to expression of previously silenced genes. This modulation has been observed to be associated with decreased expression of oncogenes such as Bcr-Abl and HER-2, induction of cell cycle arrest, promotion of apoptosis, and decreased invasion of tumor cells.[1][2][3][4][5]
Route: PO
Extravasation: n/a

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 prescribing information.[1]

Diseases for which it is used

Clinical trials

Patient drug information

History of changes in FDA indication

  • 2/23/2015: FDA accelerated approval "for the treatment of patients with multiple myeloma who have received at least 2 prior regimens, including bortezomib and an immunomodulatory agent."

Also known as

LBH589

References

  1. ↑ 1.0 1.1 1.2 Panobinostat (Farydak) package insert
  2. ↑ Panobinostat (Farydak) package insert, locally hosted backup
  3. ↑ Novartis's information about panobinostat
  4. ↑ Hasegawa H, Yamada Y, Tsukasaki K, Mori N, Tsuruda K, Sasaki D, Usui T, Osaka A, Atogami S, Ishikawa C, Machijima Y, Sawada S, Hayashi T, Miyazaki Y, Kamihira S. LBH589, a deacetylase inhibitor, induces apoptosis in adult T-cell leukemia/lymphoma cells via activation of a novel RAIDD-caspase-2 pathway. Leukemia. 2011 Apr;25(4):575-87. Epub 2011 Jan 18. link to original article PubMed
  5. ↑ Crisanti MC, Wallace AF, Kapoor V, Vandermeers F, Dowling ML, Pereira LP, Coleman K, Campling BG, Fridlender ZG, Kao GD, Albelda SM. The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cells in vitro and in vivo with particular efficacy for small cell lung cancer. Mol Cancer Ther. 2009 Aug;8(8):2221-31. Epub 2009 Aug 11. link to original article PubMed
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