Panobinostat (Farydak)

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.
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)

Preliminary data

Multiple myeloma

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

1. 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
2. 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

Waldenström macroglobulinemia

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

1. 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.