A phase i, pharmacokinetic, and pharmacodynamic study of panobinostat, an HDAC inhibitor, combined with erlotinib in patients with advanced aerodigestive tract tumors

Clinical Cancer Research

Volumn 20, Issue 6, 2014, Pages 1644-1655

  Gray, Jhanelle E ^a,d   Haura, Eric ^a,d   Chiappori, Alberto ^a,d   Tanvetyanon, Tawee ^a   Williams, Charles C ^a   Pinder Schenck, Mary ^a,d   Kish, Julie A ^b   Kreahling, Jenny ^d   Lush, Richard ^d,e   Neuger, Anthony ^d,e   Tetteh, Leticia ^c   Akar, Angela ^a   Zhao, Xiuhua ^a   Schell, Michael J ^a   Bepler, Gerold ^f   Altiok, Soner ^d  

^a H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^b Departments of Head and Neck Oncology   (United States)

^c Cutaneous Oncology Program   (United States)

^d Chemical Biology and Molecular Medicine Program Department of Genitourinary Oncology   (United States)

^e Departments of Clinical Pharmacology Core   (United States)

^f KARMANOS CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHECKPOINT KINASE 1; EPIDERMAL GROWTH FACTOR RECEPTOR; ERLOTINIB; PANOBINOSTAT; ANTINEOPLASTIC AGENT; HISTONE DEACETYLASE INHIBITOR; HYDROXAMIC ACID; INDOLE DERIVATIVE; QUINAZOLINE DERIVATIVE;

ABDOMINAL FAT ASPIRATION BIOPSY; ADULT; ADVANCED CANCER; AGED; ALOPECIA; ANOREXIA; ANXIETY DISORDER; AREA UNDER THE CURVE; ARTICLE; ASTHENIA; CANCER COMBINATION CHEMOTHERAPY; CANCER CONTROL; CANCER SURVIVAL; CHILL; CLINICAL ARTICLE; CLINICAL EFFECTIVENESS; CLINICAL EVALUATION; CONSTIPATION; COUGHING; DEHYDRATION; DESQUAMATION; DIARRHEA; DIGESTIVE SYSTEM TUMOR; DOSE RESPONSE; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DYSPNEA; FATIGUE; FEMALE; GASTRITIS; GASTROESOPHAGEAL REFLUX; HAIR LOSS; HEAD AND NECK CANCER; HEART ATRIUM FIBRILLATION; HISTONE ACETYLATION; HUMAN; HUMAN TISSUE; HYPERGLYCEMIA; HYPERTENSION; HYPOALBUMINEMIA; HYPOPHOSPHATEMIA; HYPOTHYROIDISM; INFECTION; LETHARGY; LUNG NON SMALL CELL CANCER; LYMPHOCYTOPENIA; MALAISE; MALE; MAXIMUM TOLERATED DOSE; MUCOSA INFLAMMATION; MULTIPLE CYCLE TREATMENT; MUSCLE WEAKNESS; NAUSEA; PAIN; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEIN EXPRESSION; PRURITUS; QT PROLONGATION; RASH; RIGOR; SENSORY NEUROPATHY; STOMATITIS; SURVIVAL TIME; TIME TO MAXIMUM PLASMA CONCENTRATION; VOMITING; WEIGHT REDUCTION; CARCINOMA, NON-SMALL-CELL LUNG; CLINICAL TRIAL; DISEASE FREE SURVIVAL; HEAD AND NECK NEOPLASMS; KAPLAN MEIER METHOD; LUNG NEOPLASMS; MIDDLE AGED; MORTALITY; TREATMENT OUTCOME;

AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CARCINOMA, NON-SMALL-CELL LUNG; DISEASE-FREE SURVIVAL; FEMALE; HEAD AND NECK NEOPLASMS; HISTONE DEACETYLASE INHIBITORS; HUMANS; HYDROXAMIC ACIDS; INDOLES; KAPLAN-MEIER ESTIMATE; LUNG NEOPLASMS; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; QUINAZOLINES; TREATMENT OUTCOME;

EID: 84896502954     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-13-2235     Document Type: Article

References (53)

1. Marks P, Rifkind RA, Richon VM, Breslow R, Miller T, Kelly WK. Histone deacetylases and cancer: causes and therapies. Nat Rev Cancer 2001;1:194-202.
2. Marks PA, Dokmanovic M. Histone deacetylase inhibitors: discovery and development as anticancer agents. Expert Opin Investig Drugs 2005;14:1497-511.
3. Cress WD, Seto E. Histone deacetylases, transcriptional control, and cancer. J Cell Physiol 2000;184:1-16.
4. Glozak MA, Sengupta N, Zhang X, Seto E. Acetylation and deacetylation of non-histone proteins. Gene 2005;363:15-23.
5. Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J, et al. Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Mol Cell 2006;23:607-18.
6. Lane AA, Chabner BA. Histone deacetylase inhibitors in cancer therapy. J Clin Oncol 2009;27:5459-68.
7. Yang XJ, Seto E. Lysine acetylation: codified crosstalk with other posttranslational modifications. Mol Cell 2008;31:449-61.
8. Edwards A, Li J, Atadja P, Bhalla K, Haura E. Effect of the histone deacetylase inhibitor LBH589 against epidermal growth factor receptor-dependant human lung cancer cells. Mol Cancer Ther 2007;6: 1-10.
9. Crisanti MC, Wallace AF, Kapoor V, Vandermeers F, Dowling ML, Pereira LP, et al. 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;8: 2221-31.
10. Qian DZ, Kato Y, Shabbeer S, Wei Y, Verheul HM, Salumbides B, et al. Targeting tumor angiogenesis with histone deacetylase inhibitors: the hydroxamic acid derivative LBH589. Clin Cancer Res 2006;12:634-42.
11. Floris G, Debiec-Rychter M, Sciot R, Stefan C, Fieuws S, Machiels K, et al. High efficacy of panobinostat towards human gastrointestinal stromal tumors in a xenograft mouse model. Clin Cancer Res 2009;15: 4066-76.
12. Heider U, Kaiser M, Sterz J, Zavrski I, Jakob C, Fleissner C, et al. Histone deacetylase inhibitors reduce VEGF production and induce growth suppression and apoptosis in human mantle cell lymphoma. Eur J Haematol 2006;76:42-50.
13. Giles F, Fischer T, Cortes J, Garcia-Manero G, Beck J, Ravandi F, et al. A phase I study of intravenous LBH589, a novel cinnamic hydroxamic acid analogue histone deacetylase inhibitor, in patients with refractory hematologic malignancies. Clin Cancer Res 2006;12:4628-35.
14. Rathkopf D, Wong BY, Ross RW, Anand A, Tanaka E, Woo MM, et al. A phase I study of oral panobinostat alone and in combination with docetaxel in patients with castration-resistant prostate cancer. Cancer Chemother Pharmacol 2010;66:181-9.
15. Bartek J, Lukas J. Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell 2003;3:421-9.
16. Brazelle W, Kreahling JM, Gemmer J, Ma Y, Cress WD, Haura E, et al. Histone deacetylase inhibitors downregulate checkpoint kinase 1 expression to induce cell death in non-small cell lung cancer cells. PLoS ONE 2010;5:e14335.
17. Pao W, Miller VA. Epidermal growth factor receptor mutations, smallmolecule kinase inhibitors, and non-small-cell lung cancer: current knowledge and future directions. J Clin Oncol 2005;23:2556-68.
18. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005;353:123-32.
19. Witta SE, Gemmill RM, Hirsch FR, Coldren CD, Hedman K, Ravdel L, et al. Restoring E-cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines. Cancer Res 2006;66:944-50.
20. Ozaki K, Kosugi M, Baba N, Fujio K, Sakamoto T, Kimura S, et al. Blockade of the ERK or PI3K-Akt signaling pathway enhances the cytotoxicity of histone deacetylase inhibitors in tumor cells resistant to gefitinib or imatinib. Biochem Biophys Res Commun 2010;391: 1610-5.
21. Sharma SV, Lee DY, Li B, Quinlan MP, Takahashi F, Maheswaran S, et al.Achromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell 2010;141:69-80.
22. Gao YS, Hubbert CC, Lu J, Lee YS, Lee JY, Yao TP. Histone deacetylase 6 regulates growth factor-induced actin remodeling and endocytosis. Mol Cell Biol 2007;27:8637-47.
23. Gao YS, Hubbert CC, Yao TP. The microtubule-Associated histone deacetylase 6 (HDAC6) regulates epidermal growth factor receptor (EGFR) endocytic trafficking and degradation. J Biol Chem 2010;285: 11219-26.
24. Lepper ER, Swain SM, Tan AR, Figg WD, Sparreboom A. Liquidchromatographic determination of erlotinib (OSI-774), an epidermal growth factor receptor tyrosine kinase inhibitor. J Chromatogr BAnalyt Technol Biomed Life Sci 2003;796:181-8.
25. Zhao M, He P, Rudek MA, Hidalgo M, Baker SD. Specific method for determination of OSI-774 and its metabolite OSI-420 in human plasma by using liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2003;793:413-20.
26. Hamberg P, Woo MM, Chen LC, Verweij J, Porro MG, Zhao L, et al. Effect of ketoconazole-mediated CYP3A4 inhibition on clinical pharmacokinetics of panobinostat (LBH589), an orally active histone deacetylase inhibitor. Cancer Chemother Pharmacol 2011;68:805-13.
27. Noh EJ, Lim DS, Jeong G, Lee JS. An HDAC inhibitor, trichostatin A, induces a delay at G2/Mtransition, slippage of spindle checkpoint, and cell death in a transcription-dependent manner. Biochem Biophys Res Commun 2009;378:326-31.
28. Witta SE, Jotte RM, Konduri K, Neubauer MA, Spira AI, Ruxer RL, et al. Randomized phase II trial of erlotinib with and without entinostat in patients with advanced non-small-cell lung cancer who progressed on prior chemotherapy. J Clin Oncol 2012;30:2248-55.
29. Altiok S, Brazelle W,Gemmer J, Haura E. Subcutaneous adipose tissue as a surrogate for pharmacodynamic assessment of HDAC inhibitors. In: Proceedings of the ASCO Molecular Markers Meeting; 2008; Abstract nr 123.
30. Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010;362:2380-8.
31. Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, et al. Gefitinib versus cisplatin plus docetaxel in patients with nonsmall-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 2010;11:121-8.
32. Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-smallcell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 2012;13:239-46.
33. Moore PS, Barbi S, Donadelli M, Costanzo C, Bassi C, Palmieri M, et al. Gene expression profiling after treatment with the histone deacetylase inhibitor trichostatin A reveals altered expression of both pro-And antiapoptotic genes in pancreatic adenocarcinoma cells. Biochim Biophys Acta 2004;1693:167-76.
34. Khan AN, Tomasi TB. Histone deacetylase regulation of immune gene expression in tumor cells. Immunol Res 2008;40:164-78.
35. Bridle BW, Chen L, Lemay CG, Diallo JS, Pol J, Nguyen A, et al. HDAC inhibition suppresses primary immune responses, enhances secondary immune responses, and abrogates autoimmunity during tumor immunotherapy. Mol Ther 2013;21:887-94.
36. Chaft JE, Oxnard GR, Sima CS, Kris MG, Miller VA, Riely GJ. Disease flare after tyrosine kinase inhibitor discontinuation in patients with EGFR-mutant lung cancer and acquired resistance to erlotinib or gefitinib: implications for clinical trial design. Clin Cancer Res 2011;17: 6298-303.
37. Goldberg SB, Oxnard GR, Digumarthy S, Muzikansky A, Jackman DM, Lennes IT, et al. Chemotherapy with erlotinib or chemotherapy alone in advanced non-small cell lung cancer with acquired resistance to EGFR tyrosine kinase inhibitors. Oncologist 2013;18:1214-20.
38. Heon S, Nishino M, Goldberg SB, Porter J, Sequist LV, Jackman DM, et al. Response toEGFRtyrosine kinase inhibitor (TKI) retreatment after a drug-free interval in EGFR-mutant advanced non-small cell lung cancer (NSCLC) with acquired resistance. J Clin Oncol 30, 2012 (suppl; abstr 7525).
39. Oxnard GR, Janjigian YY, Arcila ME, Sima CS, Kass SL, Riely GJ, et al. Maintained sensitivity to EGFR tyrosine kinase inhibitors in EGFRmutant lung cancer recurring after adjuvant erlotinib or gefitinib. Clin Cancer Res 2011;17:6322-8.
40. Oxnard GR, Lo P, Jackman DM, Butaney M, Heon S, Johnson BE, et al. Delay of chemotherapy through use of post-progression erlotinib in patients with EGFR-mutant lung cancer. J Clin Oncol 30, 2012 (suppl; abstr 7547).
41. Sequist LV, Waltman BA, Dias-Santagata D, Digumarthy S, Turke AB, Fidias P, et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med 2011;3: 75ra26.
42. Dragnev KH, Petty WJ, Shah S, Biddle A, Desai NB, Memoli V, et al. Bexarotene and erlotinib for aerodigestive tract cancer. J Clin Oncol 2005;23:8757-64.
43. Siu LL, Soulieres D, Chen EX, Pond GR, Chin SF, Francis P, et al. Phase I/II trial of erlotinib and cisplatin in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a Princess Margaret Hospital phase II consortium and National Cancer Institute of Canada Clinical Trials Group Study. J Clin Oncol 2007;25:2178-83.
44. Soulieres D, Senzer NN, Vokes EE, Hidalgo M, Agarwala SS, Siu LL. Multicenter phase II study of erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent or metastatic squamous cell cancer of the head and neck. J Clin Oncol 2004;22:77-85.
45. Uramoto H, Iwata T, Onitsuka T, Shimokawa H, Hanagiri T, Oyama T. Epithelial-mesenchymal transition in EGFR-TKI acquired resistant lung adenocarcinoma. Anticancer Res 2010;30:2513-7.
46. Chung JH, Rho JK, Xu X, Lee JS, Yoon HI, Lee CT, et al. Clinical and molecular evidences of epithelial to mesenchymal transition in acquired resistance to EGFR-TKIs. Lung Cancer 2011;73:176-82.
47. Yauch RL, Januario T, Eberhard DA, Cavet G, Zhu W, Fu L, et al. Epithelial versus mesenchymal phenotype determines in vitro sensitivity and predicts clinical activity of erlotinib in lung cancer patients. Clin Cancer Res 2005;11:8686-98.
48. Thomson S, Buck E, Petti F, Griffin G, Brown E, Ramnarine N, et al. Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition. Cancer Res 2005;65: 9455-62.
49. Coldren CD, Helfrich BA, Witta SE, Sugita M, Lapadat R, Zeng C, et al. Baseline gene expression predicts sensitivity to gefitinib in non-small cell lung cancer cell lines. Mol Cancer Res 2006;4:521-8.
50. Ryan QC, Headlee D, Acharya M, Sparreboom A, Trepel JB, Ye J, et al. Phase I and pharmacokinetic study of MS-275, a histone deacetylase inhibitor, in patients with advanced and refractory solid tumors or lymphoma. J Clin Oncol 2005;23:3912-22.
51. Novotny-Diermayr V, Sausgruber N, Loh YK, Pasha MK, Jayaraman R, Hentze H, et al. Pharmacodynamic evaluation of the target efficacy of SB939, an oral HDAC inhibitor with selectivity for tumor tissue. Mol Cancer Ther 2011;10:1207-17.
52. van GII, Hazenberg BP, Bijzet J, van Rijswijk MH. Diagnostic accuracy of subcutaneous abdominal fat tissue aspiration for detecting systemic amyloidosis and its utility in clinical practice. Arthritis Rheum 2006;54:2015-21.
53. van G II, Hazenberg BP, Bijzet J, Haagsma EB, Vellenga E, Posthumus MD, et al. Amyloid load in fat tissue reflects disease severity and predicts survival in amyloidosis. Arthritis Care Res 2010;62:296-301.