Difference between revisions of "Panobinostat (Farydak)"
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==Bortezomib, Dexamethasone & Panobinostat== | ==Bortezomib, Dexamethasone & Panobinostat== | ||
| − | ===Regimen, | + | ===Regimen #1, San-Miguel et al. 2014 (PANORAMA1)=== |
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| + | border-style:solid;">Phase III</span> | ||
| + | |||
| + | *[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11 | ||
| + | *[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12 | ||
| + | *[[Panobinostat (LBH589)]] 20mg PO once per day on days 1, 3, 5, 8, 10, 12 | ||
| + | |||
| + | '''21-day cycles''' | ||
| + | ===Regimen #2, Richardson et al. 2013 (PANORAMA 2)=== | ||
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===References=== | ===References=== | ||
# 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] | # 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] | ||
| + | # 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] | ||
*[[Waldenström macroglobulinemia]] | *[[Waldenström macroglobulinemia]] | ||
Revision as of 21:44, 6 October 2014
In clinical trials.
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]
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.
Clinical trials
- Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma (PANORAMA-1)
- A Study Of Panobinostat In Children With Refractory Hematologic Malignancies
- A Safety Study of LBH589 (Panobinostat) and RAD001 (Everolimus) to Stabilize Kidney Cancer
- Safety & Efficacy Study of Oral Panobinostat (LBH589) With Chemotherapy in Patients < 65 Years Old With Acute Myeloid Leukemia (AML)
Diseases for which it is used
Bortezomib, Dexamethasone & Panobinostat
Regimen #1, San-Miguel et al. 2014 (PANORAMA1)
Phase III
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
- Dexamethasone (Decadron) 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
- Panobinostat (LBH589) 20mg PO once per day on days 1, 3, 5, 8, 10, 12
21-day cycles
Regimen #2, Richardson et al. 2013 (PANORAMA 2)
Phase II
Phase 1
- Bortezomib (Velcade) 1.3 mg/m2 IV twice per week
- Dexamethasone (Decadron) 20 mg PO four times per week (day of and day after bortezomib)
- Panobinostat (LBH589) 20mg PO three times per week
2-weeks on, 1-week off x 8 cycles
Phase 2
- Bortezomib (Velcade) 1.3 mg/m2 IV once per week on weeks 1, 2, 4, 5
- Dexamethasone (Decadron) 20 mg PO twice per week on weeks 1, 2, 4, 5 (day of and day after bortezomib)
- Panobinostat (LBH589) 20mg PO three times per week on weeks 1, 2, 4, 5
6-week cycles until progression, death, or excess toxicity
References
- 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. link to original article Contains verified protocol PubMed
- 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. link to original article PubMed
Panobinostat
Regimen, Ghobrial et al. 2013
Phase II
- Panobinostat (LBH589) 30 mg PO 3 days per week (Mondays, Wednesdays, and Fridays)
28-day cycles, given until progression of disease
References
- 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. link to original article contains verified protocol PubMed
Patient drug information
No information available.
References
- ↑ Panobinostat manufacturer's website
- ↑ 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
- ↑ 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