Clinical applications of palifermin: Amelioration of oral mucositis and other potential indications

Journal of Cellular and Molecular Medicine

Volumn 17, Issue 11, 2013, Pages 1371-1384

  Vadhan Raj, Saroj ^a   Goldberg, Jenna D ^b,c   Perales, Miguel Angel ^b,c   Berger, Dietmar P ^d,e   van den Brink, Marcel R M ^b,c  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^c WEILL CORNELL MEDICAL COLLEGE   (United States)

^d AMGEN INC   (United States)

^e GENENTECH INC   (United States)

Author keywords

Dysphagia; GVHD; HSCT; Immune reconstitution; KGF; Mucositis; Oral mucositis; Palifermin; Palliative care

Indexed keywords

ANTIINFLAMMATORY AGENT; ANTINEOPLASTIC AGENT; KERATINOCYTE GROWTH FACTOR; PALIFERMIN;

ANIMAL; CHEMICALLY INDUCED DISORDER; CHEMORADIOTHERAPY; CLINICAL TRIAL (TOPIC); DYSPHAGIA; GRAFT VERSUS HOST REACTION; HEAD AND NECK TUMOR; HSCT; HUMAN; IMMUNE RECONSTITUTION; KGF; LUNG TUMOR; MUCOSA INFLAMMATION; ORAL MUCOSITIS; PALLIATIVE THERAPY; REVIEW; STOMATITIS; TREATMENT OUTCOME;

DYSPHAGIA; GVHD; HSCT; IMMUNE RECONSTITUTION; KGF; MUCOSITIS; ORAL MUCOSITIS; PALIFERMIN; PALLIATIVE CARE;

ANIMALS; ANTI-INFLAMMATORY AGENTS; ANTINEOPLASTIC AGENTS; CHEMORADIOTHERAPY; CLINICAL TRIALS AS TOPIC; DEGLUTITION DISORDERS; FIBROBLAST GROWTH FACTOR 7; HEAD AND NECK NEOPLASMS; HUMANS; LUNG NEOPLASMS; STOMATITIS; TREATMENT OUTCOME;

EID: 84891166572     PISSN: 15821838     EISSN: None     Source Type: Journal    
DOI: 10.1111/jcmm.12169     Document Type: Review

References (89)

1. Sonis ST. Oral mucositis in cancer therapy. J Support Oncol. 2004; 2: 003-8.
2. U.S. Department of Health and Human Services. Oral Health in America: a report of the surgeon general, executive summary. Rockville, MD: U.S. Department of Health and Human Services, National Institute of Dental and Craniofacial Research, National Institutes of Health; 2000.
3. Lalla RV, Sonis ST, Peterson DE. Management of oral mucositis in patients with cancer. Dent Clin North Am. 2008; 52: 61-77.
4. Sonis ST, Oster G, Fuchs H, et al. Oral mucositis and the clinical and economic outcomes of hematopoietic stem-cell transplantation. J Clin Oncol. 2001; 19: 2201-5.
5. Peterman A, Cella D, Glandon G, et al. Mucositis in head and neck cancer: economic and quality-of-life outcomes. J Natl Cancer Ins Mono. 2001; 29: 45-51.
6. Trotti A, Bellm LA, Epstein GB, et al. Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review. Radiother Oncol. 2003; 6: 253-62.
7. Elting LS, Cooksley C, Chambers M, et al. The burdens of cancer therapy: clinical and economic outcomes of chemotherapy: clinical and economic outcomes of chemotherapy-induced mucositis. Cancer. 2003; 98: 1531-9.
8. Halpern MT, Yabrof KR. Prevalence of outpatient cancer treatment in the United States: estimates from the Medical Panel Expenditures Survey (MEPS). Cancer Invest. 2008; 26: 647-51.
9. Stiff PJ. Oral mucositis therapy comes of age. J Support Oncol. 2005; 3: 73-5.
10. Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous cell carcinoma o the head and neck. N Engl J Med. 2006; 354: 567-78.
11. Elting LS, Cooksley CD, Chambers MS, et al. Risks, outcomes, and costs of radiation-induced otal mucositis among patients with head-and-neck malignancies. Int J Radiat Oncol Biol Phys. 2007; 68: 1110-20.
12. Wu JC, Beale KK, Ma JD. Evaluation of current and upcoming therapies in oral mucositis prevention. Future Oncol. 2010; 6: 1751-70.
13. D'Hondt L, Lonchay C, Andre M, et al. Oral mucositis induced by anticancer treatments: physiopathology and treatments. Ther Clin Risk Manag. 2005; 2: 159-68.
14. Vadhan-Raj S, Broxmeyer HE, Hittelman WN, et al. Abrogating chemotherapy induced myelosuppression by recombinant granulocyte-macrophage colony-stimulating facor in patients with sarcoma. Protection at the progenitor cell level. J Clin Oncol. 1992; 10: 1266-77.
15. Rubin JS, Osada H, Finch PW, et al. Purification and characterization of a newly identified growth factor specific for epithelial cells. Proc Natl Acad Sci USA. 1989; 86: 802-6.
16. Werner S. Keratinocyte growth factor: a unique player in epithelial repair processes. Cytokine Growth Factor Rev. 1998; 9: 153-65.
17. Finch PW, Rubin JS. Keratinocyte growth factor/fibroblast growth factor 7, a homeostatic factor with therapeutic potential for epithelial protection and repair. Adv Cancer Res. 2004; 91: 69-136.
18. Orr-Urtreger A, Bedford MT, Burakova T, et al. Developmental localization of the splicing alternatives of fibroblast growth factor receptor-2 (FGFR2). Dev Biol. 1993; 158: 475-86.
19. Finch PW, Cunha GR, Rubin JS, et al. Pattern of keratinocyte growth factor and keratinocyte growth factor receptor expression during mouse fetal development suggests a role in mediating morphogenetic mesenchymal-epithelial interactions. Dev Dyn. 1995; 203: 223-40.
20. Moroni E, Dell'Era P, Rusnati M, et al. Fibroblast growth factors and their receptors in hematopoiesis and hematological tumors. J Hematother Stem Cell Res. 2002; 11: 19-32.
21. Blijlevens N, Sonis S. Palifermin (recombinant keratinocyte growth factor-1): a pleiotropic growth factor with multiple biological activities in preventing chemotherapy- and radiotherapy-induced mucositis. Ann Oncol. 2007; 18: 817-26.
22. Ulich TR, Whitomb L, Tang W, et al. Keratinocyte growth factor ameliorates cyclophosphamide-induced ulcerative hemorrhagic cystitis. Cancer Res. 1997; 57: 472-5.
23. Farrell CL, Bready JV, Rex KL, et al. Keratinocyte growth factor protects mice from chemotherapy and radiation-induced gastrointestinal injury and mortality. Cancer Res. 1998; 58: 933-9.
24. Farrell CL, Rex KL, Kaufman SA, et al. Effects of keratinocyte growth factor in the squamous epithelium of the upper aerodigestive tract of normal and irradiated mice. Int J Radiat Biol. 1999; 75: 609-20.
25. Dorr W, Noack R, Spekl K, et al. Modification of oral mucositis by keratinocyte growth factor: single radiation exposure. Int J Radiat Biol. 2001; 77: 341-7.
26. Dorr W, Spekl K, Farrell CL. Amelioration of acute oral mucositis by keratinocyte growth factor: fractionated radiation. Int J Radiat Oncol Biol Phys. 2002; 54: 245-51.
27. Woo SB, Sonis ST, Monopoli MM, et al. A longitudinal study of oral ulcerative mucositis in bone marrow transplant recipients. Cancer. 1993; 72: 1612-7.
28. McGuire DB, Altomonte V, Peterson DE, et al. Patterns of mucositis and pain in patients receiving preparative chemotherapy and bone marrow transplantation. Oncol Nurs Forum. 1993; 20: 1493-502.
29. Meropol NJ, Somer RA, Gutheil J, et al. Randomized phase I trial of recombinant human keratinocyte growth factor plus chemotherapy: potential role as mucosal protectant. J Clin Oncol. 2003; 21: 1452-8.
30. Durrant S, Pico JL, Schmitz N, et al. A phase I study of recombinant keratinocyte growth factor (rHUKGF) in lymphoma patients receiving high-dose chemotherapy with autologous peripheral blood progenitor cell transplantation. Blood. 1999; 94(Suppl.): 708a, Abstract# 3130.
31. Spielberger RT, Stiff P, Emmanouilides C, et al. Efficacy of recombinant human keratinocyte growth factor (rHuKGF) in reducing mucositis in patients with hematologic malignancies undergoing autologous peripheral blood progenitor cell transplantation (auto-PBPCT) after radiation-based conditioning: results of a phase 2 trial. Proc Am Soc Clin Oncol. 2001; 20: 7a, Abstract# 25.
32. Spielberger R, Stiff P, Bensinger W, et al. Palifermin for oral mucositis after intensive therapy for hematologic cancers. N Engl J Med. 2004; 351: 2590-8.
33. Stiff PJ, Emmanouilides C, Bensinger WI, et al. Palifermin reduces patient-reported mouth and throat soreness and improves patient functioning in the hematopoietic stem-cell transplantation setting. J Clin Oncol. 2006; 24: 5186-93.
34. Elting LS, Shih YC, Stiff PJ, et al. Economic impact of palifermin on the costs of hospitalization for autologous hematopoietic stem-cell transplant: analysis of phase 3 trial results. Biol Blood Marrow Transplant. 2007; 13: 806-13.
35. Blijlevens N, de Chateau M, Krivan G, et al. In a high-dose melphalan setting, palifermin compared with placebo had no effect on oral mucositis or related patient's burden. Bone Marrow Transplant. 2013; 48: 966-71.
36. Kobbe G, Bruns I, Schroeder T, et al. A 3-day short course of palifermin before HDT reduces toxicity and need for supportive care after autologous blood stem-cell transplantation in patients with multiple myeloma. Ann Oncol. 2010; 21: 1898-904.
37. Abidi MH, Agarwal R, Tageja N, et al. A phase I dose-escalation trial of high-dose melphalan with palifermin for cytoprotection followed by autologous stem cell transplantation for patients with multiple myeloma with normal renal function. Biol Blood Marrow Transplant. 2013; 19: 56-61.
38. 2 or lower with use of palifermin for cytoprotection: results of a phase I trial. Biol Blood Marrow Transplant. 2012; 18: 1455-61.
39. Langner S, Staber P, Schub N, et al. Palifermin reduces incidence and severity of oral mucositis in allogeneic stem-cell transplant recipients. Bone Marrow Transplant. 2008; 42: 275-9.
40. Nasilowska-Adamska B, Rzepecki P, Manko J, et al. The influence of palifermin (Kepivance) on oral mucositis and acute graft versus host disease in patients with hematological diseases undergoing hematopoietic stem cell transplant. Bone Marrow Transplant. 2007; 40: 983-8.
41. van der Velden WJFM, Herbers AHE, Blijlevens NMA. Palifermin in allogeneic HSCT: many questions remain. Bone Marrow Transplant. 2009; 43: 85-6.
42. Gibson RJ, Keefe DM, Clarke JM, et al. The effect of keratinocyte growth factor on tumor growth and small intestinal mucositis after chemotherapy in the rat with breast cancer. Cancer Chemother Pharmacol. 2002; 50: 53-8.
43. Schmidt E, Thoennissen NH, Rudat A, et al. Use of palifermin for the prevention of high-dose methotrexate-induced oral mucositis. Ann Oncol. 2008; 19: 1644-9.
44. Krijanovski OI, Hill GR, Cooke KR, et al. Keratinocyte growth factor separates graft-versus-leukemia effects from graft-versus-host disease. Blood. 1999; 94: 825-31.
45. Panoskaltsis-Mortari A, Lacey DL, Vallera DA, et al. Keratinocyte growth factor administered before conditioning ameliorates graft-versus-host disease after allogeneic bone marrow transplantation in mice. Blood. 1998; 92: 3960-7.
46. Panoskaltsis-Mortari A, Taylor PA, Rubin JS, et al. Keratinocyte growth factor facilitates alloengraftment and ameliorates graft-versus-host disease in mice by a mechanism independent of repair of conditioning-induced tissue injury. Blood. 2000; 96: 4350-6.
47. Ziegler TR, Panoskaltsus-Mortari A, Gu LH, et al. Regulation of glutathione redox status in lung and liver by conditioning regimens and keratinocyte growth factor in murine allogeneic bone marrow transplantation. Transplantation. 2001; 72: 1354-62.
48. Blazar BR, Weisdorf DJ, Defor T, et al. Phase 1/2 randomized, placebo-control trial of palifermin to prevent graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Blood. 2006; 108: 3216-22.
49. Goldberg JD, Zheng J, Castro-Malaspina H, et al. Palifermin is efficacious in recipients of TBI-based but not chemotherapy-based allogeneic hematopoietic stem cell transplants. Bone Marrow Transplant. 2013; 48: 99-104.
50. Morris J, Neudorf S, Moore T, et al. A phase I dose-escalation study to evaluate the safety and pharmacokinetics of palifermin in pediatric subjects with acute leukemias undergoing myeloablative therapy and allogeneic hematopoietic stem cell transplant. Biol Blood Marrow Transplant. 2010; 16: S256-7, Abstract# 268.
51. Srinivasan A, Kasow KA, Cross S, et al. Phase I study of the tolerability and pharmacokinetics of palifermin in children undergoing allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2012; 18: 1309-14.
52. Powles R, Singhal S, Treleaven J, et al. Identification of patients who may benefit from prophylactic immunotherapy after bone marrow transplantation for acute myeloid leukemia on the basis of lymphocyte recovery early after transplantation. Blood. 1998; 91: 3481-6.
53. Chakrabarti S, Brown J, Guttridge M, et al. Early lymphocyte recovery is an important determinant of outcome following allogeneic transplantation with CD34 + selected graft and limited T-cell add back. Bone Marrow Transplant. 2003; 32: 23-30.
54. Savani BN, Mielke S, Rezvani K, et al. Absolute lymphocyte count on day 30 is a surrogate for robust hematopoietic recovery and strongly predicts outcome after T cell-depleted allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2007; 13: 1216-23.
55. Small TN, Papadopoulos EB, Boulad F, et al. Comparison of immune reconstitution after unrelated and related T-cell-depleted bone marrow transplantation: effect of patient age and donor leukocyte infusions. Blood. 1999; 93: 467-80.
56. Goldberg JD, Zheng J, Barker J, et al. Early immune recovery predicts overall and disease-free survival after allogeneic hematopoietic stem cell transplantation. Blood (ASH Annual Meeting Abstracts). 2009; 114: 875-6, Abstract# 2222.
57. Alpdogan O, Hubbard VM, Smith OM, et al. Keratinocyte growth factor (KGF) is required for postnatal thymic regeneration. Blood. 2006; 107: 2453-60.
58. Jenq RR, King CG, Volk C, et al. Keratinocyte growth factor enhances DNA plasmid tumor vaccine responses after murine allogeneic bone marrow transplantation. Blood. 2009; 113: 1574-80.
59. Rossi SW, Blazar BR, Farrell CL, et al. Keratinocyte growth factor preserves normal thymopoiesis and thymic microenvironment during experimental graft-versus-host disease. Blood. 2002; 100: 682-91.
60. Wang Y, Chen G, Qiao S, et al. Keratinocyte growth factor enhanced immune reconstitution in murine allogeneic umbilical cord blood cell transplant. Leuk Lymphoma. 2011; 52: 1556-66.
61. Kelly RM, Highfill SL, Panoskaltsis-Mortari A, et al. Keratinocyte growth factor and androgen blockade work in concert to protect against conditioning regimen-induced thymic epithelial damage and enhance T-cell reconstitution after murine bone marrow transplantation. Blood. 2008; 111: 5734-44.
62. Kelly RM, Goren EM, Taylor PA, et al. Short-term inhibition of p53 combined with keratinocyte growth factor improves thymic epithelial cell recovery and enhances T-cell reconstitution after murine bone marrow transplantation. Blood. 2010; 115: 1088-97.
63. Seggewiss R, Lore K, Guenaga FJ, et al. Keratinocyte growth factor augments immune reconstitution after autologous hematopoietic progenitor cell transplantation in rhesus macaques. Blood. 2007; 110: 441-9.
64. Rizwan R, Levine JE, Defor T, et al. Peritransplant palifermin use and lymphocyte recovery after T-cell replete, matched related allogeneic hematopoietic cell transplantation. Am J Hematol. 2011; 86: 879-82.
65. Hill GR, Crawford JM, Cooke KR, et al. Total body irradiation and acute graft-versus-host disease: the role of gastrointestinal damage and inflammatory cytokines. Blood. 1997; 90: 3204-13.
66. Cooke KR, Hill GR, Crawford JM, et al. Tumor necrosis factor-alpha production to lipopolysaccharide stimulation by donor cells predicts the severity of experimental acute graft-versus-host disease. J Clin Invest. 1998; 102: 1882-91.
67. Levine JE, Blazar BR, DeFor T, et al. Long-term follow-up of a phase I/II randomized, placebo-controlled trial of palifermin to prevent graft-versus-host disease (GVHD) after related donor allogeneic hematopoietic cell transplantation (HCT). Biol Blood Marrow Transplant. 2008; 14: 1017-21.
68. Nasilowska-Adamska B, Szydlo R, Rzepecki P, et al. Palifermin does not influence the incidence and severity of GvHD nor long-term survival of patients with hematological diseases undergoing HSCT. Ann Transplant. 2011; 16: 47-54.
69. Jagasia MH, Abonour R, Long GD, et al. Palifermin for the reduction of acute GVDH: a randomized, double-blind, placebo-controlled trial. Bone Marrow Transplant. 2012; 47: 1350-5.
70. Brizel DM, Murphy BA, Rosenthal DI, et al. Phase II study of palifermin and concurrent chemoradiation in head and neck squamous cell carcinoma. J Clin Oncol. 2008; 26: 2489-96.
71. Henke M, Alfonsi M, Foa P, et al. Palifermin decreases severe oral mucositis of patients undergoing postoperative radiochemotherapy or head and neck cancer: a randomized, placebo-controlled trial. J Clin Oncol. 2011; 29: 2815-20.
72. Le Q-T, Kim HE, Schneider CJ, et al. Palifermin reduces severe mucositis in definitive chemoradiotherapy of locally advanced head and neck cancer: a randomized, placebo-controlled study. J Clin Oncol. 2011; 29: 2808-14.
73. Belderbos J, Uitterhoeve L, van Zandwijk N, et al. Randomised trial of sequential versus concurrent chemo-radiotherapy in patients with inoperable non-small cell lung cancer (EORTC 08972-22973). Eur J Cancer. 2007; 43: 114-21.
74. Fournel P, Robinet G, Thomas P, et al. Randomized phase III trial of sequential chemoradiotherapy compared with concurrent chemoradiotherapy in locally advanced non-small-cell lung cancer: Groupe Lyon-Saint-Etienne d'Oncologie Thoracique-Groupe Francais de Pneumo-Cancerologie NPC 95-01 Study. J Clin Oncol. 2005; 23: 5910-7.
75. Kepka L, Sprawka A, Casas F, et al. Combination of radiotherapy and chemotherapy in locally advanced NSCLC. Expert Rev Anticancer Ther. 2009; 9: 1389-403.
76. Zatloukal P, Petruzelka L, Zemanova M, et al. Concurrent versus sequential chemoradiotherapy with cisplatin and vinorelbine in locally advanced non-small cell lung cancer: a randomized study. Lung Cancer. 2004; 46: 87-98.
77. Lau D, Leigh B, Gandara D, et al. Twice-weekly paclitaxel and weekly carboplatin with concurrent thoracic radiation followed by carboplatin/paclitaxel consolidation for stage III non-small-cell lung cancer: a California Cancer Consortium phase II trial. J Clin Oncol. 2001; 19: 442-7.
78. Vokes EE, Herndon JE 2nd, Crawford J, et al. Randomized phase II study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy for stage IIIB non-small-cell lung cancer: cancer and leukemia group B study 9431. J Clin Oncol. 2002; 20: 4191-8.
79. Werner-Wasik M. Treatment-related esophagitis. Semin Oncol. 2005; 32: S60-6.
80. Schuette W, Krzakowski MJ, Massuti B, et al. Randomized phase II study of palifermin for reducing dysphagia in patients receiving concurrent chemoradiotherapy for locally advanced unresectable non-small cell lung cancer. J Thorac Oncol. 2012; 7: 157-64.
81. Bradley J. A review of radiation dose escalation trials for non-small cell lung cancer within the Radiation Therapy Oncology Group. Semin Oncol. 2005; 32: S111-3.
82. Hazuka MB, Turrisi AT 3rd, Lutz ST, et al. Results of high-dose thoracic irradiation incorporating beam's eye view display in non-small cell lung cancer: a retrospective multivariate analysis. Int J Radiat Oncol Biol Phys. 1993; 27: 273-84.
83. Perez CA, Stanley K, Rubin P, et al. A prospective randomized study of various irradiation doses and fractionation schedules in the treatment of inoperable non-oat-cell carcinoma of the lung. Preliminary report by the Radiation Therapy Oncology Group. Cancer. 1980; 45: 2744-53.
84. Rosen LS, Abdi E, Davis ID, et al. Palifermin reduces the incidence of oral mucositis in patients with metastatic colorectal cancer treated with fluorouracil-based chemotherapy. J Clin Oncol. 2006; 2: 5194-200.
85. Patel SR, Vadhan-Raj S, Burguess MA, et al. Results of two consecutive trials of dose-intensive chemotherapy with doxorubicin and ifosfamide in patients with sarcomas. Amer J Clin Oncol. 1998; 21: 317-21.
86. Vadhan-Raj S, Patel S, Bueso-Ramos CE, et al. Importance of pre-dosing of recombinant human thrombopoietin to reduce chemotherapy-induced early thrombocytopenia. J Clin Oncol. 2003; 21: 3158-67.
87. Vadhan-Raj S, Trent J, Patel S, et al. Single-dose palifermin prevents severe oral mucositis during multicycle chemotherapy in patients with cancer. A randomized trial. Annals Int Med. 2010; 153: 358-67.
88. Keijzer A, Huijgens PC, van de Loosdrecht AA. Palifermin and palmar-plantar erythrodysesthesia. Br J Haematol. 2007; 136: 856-7.
89. Milne O, Cutts B, LcLean C, et al. Palifermin-induced acral erythrodysaesthesia variant in the treatment of acute myeloid leukaemia. Australas J Dermatol. 2011; 52: 59-61.