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Systematic review of growth factors and cytokines for the management of oral mucositis in cancer patients and clinical practice guidelines

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Abstract

Purpose

To update the clinical practice guidelines for the use of growth factors and cytokines for the prevention and/or treatment of oral mucositis (OM).

Methods

A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, the following guidelines were determined: recommendation, suggestion, and no guideline possible.

Results

A total of 15 new papers were identified within the scope of this section and were merged with 51 papers that were reviewed in the previous guidelines update. Of these, 14, 5, 13, 2, and 1 were randomized controlled trials about KGF-1, G-CSF, GM-CSF, EGF, and erythropoietin, respectively. For the remaining agents there were no new RCTs. The previous recommendation for intravenous KGF-1 in patients undergoing autologous hematopoietic stem cell transplantation (HSCT) conditioned with high-dose chemotherapy and TBI-based regimens is confirmed. The previous suggestion against the use of topical GM-CSF for the prevention of OM in the setting of high-dose chemotherapy followed by autologous or allogeneic stem cell transplantation remains unchanged.

Conclusions

Of the growth factors and cytokines studied for the management of OM, the evidence supports a recommendation in favor of KGF-1 and a suggestion against GM-CSF in certain clinical settings.

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References

  1. Abitbol AA, Sridhar KS, Lewin AA, Schwade JG, Raub W Jr, Wolfson A, Gonzalez-Angulo C, Adessa A, Goodwin WJ, Markoe AM (1997) Hyperfractionated radiation therapy and 5-fluorouracil, cisplatin, and mitomycin-C (+/- granulocyte-colony stimulating factor) in the treatment of patients with locally advanced head and neck carcinoma. Cancer 80:266–276

    Article  CAS  PubMed  Google Scholar 

  2. Bez C, Demarosi F, Sardella A, Lodi G, Bertolli VG, Annaloro C, Rimondini L, Porter SR, Carrassi A (1999) GM-CSF mouthrinses in the treatment of severe oral mucositis: a pilot study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 88:311–315

    Article  CAS  PubMed  Google Scholar 

  3. Bianchi L, Ginebri A, Hagman JH, Francesconi F, Carboni I, Chimenti S (2002) Local treatment of chronic cutaneous leg ulcers with recombinant human granulocyte-macrophage colony-stimulating factor. J Eur Acad Dermatol Venereol 16:595–598

    Article  CAS  PubMed  Google Scholar 

  4. Blazar BR, Weisdorf DJ, DeFor T, Goldman A, Braun T, Silver S, Ferrara JL (2006) Phase 1/2 randomized, placebo-control trial of palifermin to prevent graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Blood 108:3216–3222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Blijlevens N, de Chateau M, Krivan G, Rabitsch W, Szomor A, Pytlik R, Lissmats A, Johnsen HE, de Witte T, Einsele H, Ruutu T, Niederwieser D (2013) In a high-dose melphalan setting, palifermin compared with placebo had no effect on oral mucositis or related patient's burden. Bone marrow transplantation 48:966–971

    Article  CAS  PubMed  Google Scholar 

  6. Bradstock KF, Link E, Collins M, Di Iulio J, Lewis ID, Schwarer A, Enno A, Marlton P, Hahn U, Szer J (2014) A randomized trial of prophylactic palifermin on gastrointestinal toxicity after intensive induction therapy for acute myeloid leukaemia. Br J Haematol 167:618–625

    Article  CAS  PubMed  Google Scholar 

  7. Bradstock KF, Link E, Collins M, Di Iulio J, Lewis ID, Schwarer A, Enno A, Marlton P, Hahn U, Szer JJBjoh (2014) A randomized trial of prophylactic palifermin on gastrointestinal toxicity after intensive induction therapy for acute myeloid leukaemia. Br J Haematol 167:618–625

    Article  CAS  PubMed  Google Scholar 

  8. Brizel DM, Murphy BA, Rosenthal DI, Pandya KJ, Glück S, Brizel HE, Meredith RF, Berger D, Chen M-G, Mendenhall W (2008) Phase II study of palifermin and concurrent chemoradiation in head and neck squamous cell carcinoma. J Clin Oncol 26:2489–2496

    Article  CAS  PubMed  Google Scholar 

  9. Broxmeyer HE (2013) Erythropoietin: multiple targets, actions, and modifying influences for biological and clinical consideration. J Exp Med 210:205–208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Cantarelli C, Angeletti A, Cravedi P (2019) Erythropoietin, a multifaceted protein with innate and adaptive immune modulatory activity American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

  11. Cartee L, Petros WP, Rosner GL, Gilbert C, Moore S, Affronti ML, Hoke JA, Hussein AM, Ross M, Rubin P et al (1995) Evaluation of GM-CSF mouthwash for prevention of chemotherapy-induced mucositis: a randomized, double-blind, dose-ranging study. Cytokine 7:471–477

    Article  CAS  PubMed  Google Scholar 

  12. Chi KH, Chen CH, Chan WK, Chow KC, Chen SY, Yen SH, Chao JY, Chang CY, Chen KY (1995) Effect of granulocyte-macrophage colony-stimulating factor on oral mucositis in head and neck cancer patients after cisplatin, fluorouracil, and leucovorin chemotherapy. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 13:2620–2628

    Article  CAS  Google Scholar 

  13. Crawford J, Tomita DK, Mazanet R, Glaspy J, Ozer H (1999) Reduction of oral mucositis by filgrastim (r-metHuG-CSF) in patients receiving chemotherapy. Cytokines Cell Mol Ther 5:187–193

    CAS  PubMed  Google Scholar 

  14. Czyzewski K, Debski R, Krenska A, Wysocki M, Styczynski J (2014) Palifermin in children undergoing autologous stem cell transplantation: a matched-pair analysis. Anticancer Res 34:7379–7382

    CAS  PubMed  Google Scholar 

  15. Dazzi C, Cariello A, Giovanis P, Monti M, Vertogen B, Leoni M, Tienghi A, Turci D, Rosti G, Nanni O, Rondoni C, Marangolo M (2003) Prophylaxis with GM-CSF mouthwashes does not reduce frequency and duration of severe oral mucositis in patients with solid tumors undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue: a double blind, randomized, placebo-controlled study. Ann Oncol 14:559–563

    Article  CAS  PubMed  Google Scholar 

  16. Ellis GK, Barlow WE, Gralow JR, Hortobagyi GN, Russell CA, Royce ME, Perez EA, Lew D, Livingston RB (2011) Phase III comparison of standard doxorubicin and cyclophosphamide versus weekly doxorubicin and daily oral cyclophosphamide plus granulocyte colony-stimulating factor as neoadjuvant therapy for inflammatory and locally advanced breast cancer: SWOG 0012. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 29:1014–1021

    Article  CAS  Google Scholar 

  17. Kepivance. Accessed 28 July 2019, from https://www.ema.europa.eu/en/medicines/human/EPAR/kepivance.

  18. Kepivance: withdrawal of the marketing authorisation in the European Union. Accessed 28 July 2019, from https://www.ema.europa.eu/en/documents/public-statement/public-statement-kepivance-withdrawal-marketing-authorisation-european-union_en.pdf].

  19. Epstein JB, Thariat J, Bensadoun RJ, Barasch A, Murphy BA, Kolnick L, Popplewell L, Maghami E (2012) Oral complications of cancer and cancer therapy: from cancer treatment to survivorship. CA: a cancer journal for clinicians 62:400–422

    Google Scholar 

  20. Farrell C, Rex K, Chen J, Bready J, DiPalma C, Kaufman S, Rattan A, Scully S, Lacey D (2002) The effects of keratinocyte growth factor in preclinical models of mucositis. Cell proliferation 35:78–85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Freytes CO, Ratanatharathorn V, Taylor C, Abboud C, Chesser N, Restrepo A, Arango J, Odenheimer D (2004) Phase I/II randomized trial evaluating the safety and clinical effects of repifermin administered to reduce mucositis in patients undergoing autologous hematopoietic stem cell transplantation. Clin Cancer Res 10:8318–8324

    Article  CAS  PubMed  Google Scholar 

  22. Gholizadeh N, Mehdipoor M, Sajadi H, Moosavi M-S (2016) Palifermin and chlorhexidine mouthwashes in prevention of chemotherapy-induced mucositis in children with acute lymphocytic leukemia: a randomized controlled trial. Journal of Dentistry 17:343

    PubMed  PubMed Central  Google Scholar 

  23. Girdler NM, McGurk M, Aqual S, Prince M (1995) The effect of epidermal growth factor mouthwash on cytotoxic-induced oral ulceration. A phase I clinical trial Am J Clin Oncol 18:403–406

    Article  CAS  PubMed  Google Scholar 

  24. Goldberg JD, Zheng J, Castro-Malaspina H, Jakubowski AA, Heller G, van den Brink MR, Perales M-A (2013) Palifermin is efficacious in recipients of TBI-based but not chemotherapy-based allogeneic hematopoietic stem cell transplants. Bone Marrow Transplant 48:99

    Article  CAS  PubMed  Google Scholar 

  25. Gordon B, Spadinger A, Hodges E, Ruby E, Stanley R, Coccia PJJoCO (1994) Effect of granulocyte-macrophage colony-stimulating factor on oral mucositis after hematopoietic stem-cell transplantation. J Clin Oncol 12:1917–1922

    Article  CAS  PubMed  Google Scholar 

  26. Hadorn DC, Baker D, Hodges JS, Hicks N (1996) Rating the quality of evidence for clinical practice guidelines. J Clin Epidemiol 49:749–754

    Article  CAS  PubMed  Google Scholar 

  27. Hamed S, Bennett CL, Demiot C, Ullmann Y, Teot L, Desmouliere A (2014) Erythropoietin, a novel repurposed drug: an innovative treatment for wound healing in patients with diabetes mellitus. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society 22:23–33

    Article  Google Scholar 

  28. Hejna M, Kostler WJ, Raderer M, Steger GG, Brodowicz T, Scheithauer W, Wiltschke C, Zielinski CC (2001) Decrease of duration and symptoms in chemotherapy-induced oral mucositis by topical GM-CSF: results of a prospective randomised trial. Eur J Cancer 37:1994–2002

    Article  CAS  PubMed  Google Scholar 

  29. Henke M, Alfonsi M, Foa P, Giralt J, Bardet E, Cerezo L, Salzwimmer M, Lizambri R, Emmerson L, Chen M-G (2011) Palifermin decreases severe oral mucositis of patients undergoing postoperative radiochemotherapy for head and neck cancer: a randomized, placebo-controlled trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 29:–2815, 2820

  30. Hoffman KE, Pugh SL, James JL, Scarantino C, Movsas B, Valicenti RK, Fortin A, Pollock J, Kim H, Brachman DG, Berk LB, Bruner DW, Kachnic LA (2014) The impact of concurrent granulocyte-macrophage colony-stimulating factor on quality of life in head and neck cancer patients: results of the randomized, placebo-controlled Radiation Therapy Oncology Group 9901 trial. Qual Life Res 23:1841–1858

    Article  PubMed  PubMed Central  Google Scholar 

  31. Hong J, Lee SW, Song S, Ahn S, Shin S, Choi E, Kim J (2009) Recombinant human epidermal growth factor treatment of radiation-induced severe oral mucositis in patients with head and neck malignancies. European journal of cancer care 18:636–641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Horsley P, Bauer JD, Mazkowiack R, Gardner R, Bashford J (2007) Palifermin improves severe mucositis, swallowing problems, nutrition impact symptoms, and length of stay in patients undergoing hematopoietic stem cell transplantation. Support Care Cancer 15:105–109

    Article  PubMed  Google Scholar 

  33. Hosseinjani H, Hadjibabaie M, Gholami K, Javadi M, Radfar M, Jahangard-Rafsanjani Z, Hosseinjani E, Shabani N, Vaezi M, Ghavamzadeh A (2017) The efficacy of erythropoietin mouthwash in prevention of oral mucositis in patients undergoing autologous hematopoietic SCT: a double-blind, randomized, placebo-controlled trial. Hematol Oncol 35:106–112

    Article  CAS  PubMed  Google Scholar 

  34. Ibrahim EM, al-Mulhim FA (1997) Effect of granulocyte-macrophage colony-stimulating factor on chemotherapy-induced oral mucositis in non-neutropenic cancer patients. Med Oncol 14:47–51

    Article  CAS  PubMed  Google Scholar 

  35. Ifrah N, Witz F, Jouet JP, Francois S, Lamy T, Linassier C, Pignon B, Berthou C, Guyotat D, Cahn JY, Harousseau JL (1999) Intensive short term therapy with granulocyte-macrophage-colony stimulating factor support, similar to therapy for acute myeloblastic leukemia, does not improve overall results for adults with acute lymphoblastic leukemia. GOELAMS Group Cancer 86:1496–1505

    CAS  PubMed  Google Scholar 

  36. Johansson JE, Hasseus B, Johansson P, Eklof C, Ohman D, Stockelberg D (2009) Gut protection by palifermin during autologous haematopoietic. SCT Bone Marrow Transplant 43:807–811

    Article  CAS  PubMed  Google Scholar 

  37. Jyung RW, Wu L, Pierce GF, Mustoe TA (1994) Granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor: differential action on incisional wound healing. Surgery 115:325–334

    CAS  PubMed  Google Scholar 

  38. Kannan V, Bapsy PP, Anantha N, Doval DC, Vaithianathan H, Banumathy G, Reddy KB, Kumaraswamy SV, Shenoy AM (1997) Efficacy and safety of granulocyte macrophage-colony stimulating factor (GM-CSF) on the frequency and severity of radiation mucositis in patients with head and neck carcinoma. Int J Radiat Oncol Biol Phys 37:1005–1010

    Article  CAS  PubMed  Google Scholar 

  39. Karthaus M, Rosenthal C, Huebner G, Paul H, Elser C, Hertenstein B, Krauter J, Scharmann T, Geissler RG, Heil G, Ganser A (1998) Effect of topical oral G-CSF on oral mucositis: a randomised placebo-controlled trial. Bone Marrow Transplant 22:781–785

    Article  CAS  PubMed  Google Scholar 

  40. Katano M, Nakamura M, Matsuo T, Iyama A, Hisatsugu T (1995) Effect of granulocyte colony-stimulating factor (G-CSF) on chemotherapy-induced oral mucositis. Surg Today 25:202–206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Keefe D, Lees J, Horvath N (2006) Palifermin for oral mucositis in the high-dose chemotherapy and stem cell transplant setting: the Royal Adelaide Hospital Cancer Centre experience. Support Care Cancer 14:580–582

    Article  PubMed  Google Scholar 

  42. Kim J-W, Kim MG, Lee HJ, Koh Y, Kwon J-H, Kim I, Park S, Kim BK, Oh JM, Im Kim K (2017) Topical recombinant human epidermal growth factor for oral mucositis induced by intensive chemotherapy with hematopoietic stem cell transplantation: final analysis of a randomized, double-blind, placebo-controlled, phase 2 trial. PloS one 12:e0168854

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Kim KI, Kim JW, Lee HJ, Kim BS, Bang SM, Kim I, Oh JM, Yoon SS, Lee JS, Park S (2013) Recombinant human epidermal growth factor on oral mucositis induced by intensive chemotherapy with stem cell transplantation. Am J Hematol 88:107–112

    Article  CAS  PubMed  Google Scholar 

  44. Kobbe G, Bruns I, Schroeder T, Czibere A, Warnecke J, Hieronimus N, Safaian N, Kondakci M, Saure C, Germing U, Haas R, Fenk R (2010) 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 21:1898–1904

    Article  CAS  PubMed  Google Scholar 

  45. Lalla RV, Bowen J, Barasch A, Elting L, Epstein J, Keefe DM, McGuire DB, Migliorati C, Nicolatou-Galitis O, Peterson DE, Raber-Durlacher JE, Sonis ST, Elad S (2014) MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 120:1453–1461

    Article  PubMed  Google Scholar 

  46. Langner S, Staber P, Schub N, Gramatzki M, Grothe W, Behre G, Rabitsch W, Urban C, Linkesch W, Neumeister P (2008) Palifermin reduces incidence and severity of oral mucositis in allogeneic stem-cell transplant recipients. Bone Marrow Transplant 42:275–279

    Article  CAS  PubMed  Google Scholar 

  47. Lauritano D, Petruzzi M, Di Stasio D, Lucchese A (2014) Clinical effectiveness of palifermin in prevention and treatment of oral mucositis in children with acute lymphoblastic leukaemia: a case-control study. Int J Oral Sci 6:27–30

    Article  CAS  PubMed  Google Scholar 

  48. Le Q-T, Kim HE, Schneider CJ, Muraközy G, Skladowski K, Reinisch S, Chen Y, Hickey M, Mo M, Chen M-G (2011) Palifermin reduces severe mucositis in definitive chemoradiotherapy of locally advanced head and neck cancer: a randomized, placebo-controlled study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 29:2808–2814

    Article  CAS  Google Scholar 

  49. Logan RM, Stringer AM, Bowen JM, Yeoh AS-J, Gibson RJ, Sonis ST, Keefe DM (2007) The role of pro-inflammatory cytokines in cancer treatment-induced alimentary tract mucositis: pathobiology, animal models and cytotoxic drugs. Cancer Treatment Rev 33:448–460

    Article  CAS  Google Scholar 

  50. Lucchese A, Matarese G, Ghislanzoni LH, Gastaldi G, Manuelli M, Gherlone EJL, lymphoma (2016) Efficacy and effects of palifermin for the treatment of oral mucositis in patients affected by acute lymphoblastic leukemia. 57:820–827

  51. Lucchese A, Matarese G, Manuelli M, Ciuffreda C, Bassani L, Isola G, CordaSco G, Gherlone EJM (2016) Reliability and efficacy of palifermin in prevention and management of oral mucositis in patients with acute lymphoblastic leukemia: a randomized, double-blind controlled clinical trial. Surgery 65:43–50

    Google Scholar 

  52. Makkonen TA, Minn H, Jekunen A, Vilja P, Tuominen J, Joensuu H (2000) Granulocyte macrophage-colony stimulating factor (GM-CSF) and sucralfate in prevention of radiation-induced mucositis: a prospective randomized study. Int J Radiat Oncol Biol Phys 46:525–534

    Article  CAS  PubMed  Google Scholar 

  53. Mantovani G, Massa E, Astara G, Murgia V, Gramignano G, Lusso MR, Camboni P, Ferreli L, Mocci M, Perboni S, Mura L, Madeddu C, Maccio A (2003) Phase II clinical trial of local use of GM-CSF for prevention and treatment of chemotherapy- and concomitant chemoradiotherapy-induced severe oral mucositis in advanced head and neck cancer patients: an evaluation of effectiveness, safety and costs. Oncol Rep 10:197–206

    CAS  PubMed  Google Scholar 

  54. Mascarin M, Franchin G, Minatel E, Gobitti C, Talamini R, De Maria D, Trovo MG (1999) The effect of granulocyte colony-stimulating factor on oral mucositis in head and neck cancer patients treated with hyperfractionated radiotherapy. Oral Oncol 35:203–208

    Article  CAS  PubMed  Google Scholar 

  55. Masucci G, Broman P, Kelly C, Lindahl S, Malmberg L, Reizenstein J, Alenius M, Lewensohn R (2005) Therapeutic efficacy by recombinant human granulocyte/monocyte-colony stimulating factor on mucositis occurring in patients with oral and oropharynx tumors treated with curative radiotherapy: a multicenter open randomized phase III study. Med Oncol 22:247–256

    Article  PubMed  Google Scholar 

  56. McAleese JJ, Bishop KM, A'Hern R, Henk JM (2006) Randomized phase II study of GM-CSF to reduce mucositis caused by accelerated radiotherapy of laryngeal cancer. Br J Radiol 79:608–613

    Article  CAS  PubMed  Google Scholar 

  57. Meropol NJ, Somer RA, Gutheil J, Pelley RJ, Modiano MR, Rowinsky EK, Rothenberg ML, Redding SW, Serdar CM, Yao B (2003) Randomized phase I trial of recombinant human keratinocyte growth factor plus chemotherapy: potential role as mucosal protectant. J Clin Oncol 21:1452–1458

    Article  CAS  PubMed  Google Scholar 

  58. Morris J, Rudebeck M, Neudorf S, Moore T, Duerst R, Shah AJ, Graham M, Aquino V, Morris C, Olsson B (2016) Safety, pharmacokinetics, and efficacy of palifermin in children and adolescents with acute leukemias undergoing myeloablative therapy and allogeneic hematopoietic stem cell transplantation: a pediatric blood and marrow transplant consortium trial. Biol Blood Marrow Transplant 22:1247–1256

    Article  CAS  PubMed  Google Scholar 

  59. Nasilowska-Adamska B, Rzepecki P, Manko J, Czyz A, Markiewicz M, Federowicz I, Tomaszewska A, Piatkowska-Jakubas B, Wrzesien-Kus A, Bieniaszewska M (2007) 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 40:983

    Article  CAS  PubMed  Google Scholar 

  60. Nemunaitis J, Rosenfeld CS, Ash R, Freedman MH, Deeg HJ, Appelbaum F, Singer JW, Flomenberg N, Dalton W, Elfenbein GJ et al (1995) Phase III randomized, double-blind placebo-controlled trial of rhGM-CSF following allogeneic bone marrow transplantation. Bone Marrow Transplant 15:949–954

    CAS  PubMed  Google Scholar 

  61. Nguyen DT, Shayani S, Palmer J, Dagis A, Forman SJ, Epstein J, Spielberger R (2015) Palifermin for prevention of oral mucositis in allogeneic hematopoietic stem cell transplantation: a single-institution retrospective evaluation. Support Care Cancer 23:3141–3147

    Article  PubMed  Google Scholar 

  62. Nicolatou O, Sotiropoulou-Lontou A, Skarlatos J, Kyprianou K, Kolitsi G, Dardoufas K (1998) A pilot study of the effect of granulocyte-macrophage colony-stimulating factor on oral mucositis in head and neck cancer patients during X-radiation therapy: a preliminary report. Int J Radiat Oncol Biol Phys 42:551–556

    Article  CAS  PubMed  Google Scholar 

  63. Noguchi S, Ohba Y, Oka T (1991) Effect of salivary epidermal growth factor on wound healing of tongue in mice. Am J Physiol 260:E620–E625

    CAS  PubMed  Google Scholar 

  64. Patte C, Laplanche A, Bertozzi AI, Baruchel A, Frappaz D, Schmitt C, Mechinaud F, Nelken B, Boutard P, Michon J (2002) Granulocyte colony-stimulating factor in induction treatment of children with non-Hodgkin’s lymphoma: a randomized study of the French Society of Pediatric Oncology. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20:441–448

    CAS  Google Scholar 

  65. Pietri E, Andreis D, Fabbri F, Menna C, Schirone A, Kopf B, Rocca A, Amadori D, De Giorgi U (2015) A phase II study of a dose-density regimen with fluorouracil, epirubicin, and cyclophosphamide on days 1 and 4 every 14 days with filgrastim support followed by weekly paclitaxel in women with primary breast cancer. Oncologist 20:239–240

    Article  PubMed  PubMed Central  Google Scholar 

  66. Raber-Durlacher JE, Von Bültzingslöwen I, Logan RM, Bowen J, Al-Azri AR, Everaus H, Gerber E, Gomez JG, Pettersson BG, Soga Y (2013) Systematic review of cytokines and growth factors for the management of oral mucositis in cancer patients. Supportive Care in Cancer 21:343–355

    Article  PubMed  Google Scholar 

  67. Ranna V, Cheng KKF, Castillo DA, Porcello L, Vaddi A, Lalla RV, Bossi P, Elad S (2019) Development of the MASCC/ISOO clinical practice guidelines for mucositis: an overview of the methods Support Care Cancer

  68. Rosen LS, Abdi E, Davis ID, Gutheil J, Schnell FM, Zalcberg J, Cesano A, Gayko U, Chen M-G, Clarke S (2006) Palifermin reduces the incidence of oral mucositis in patients with metastatic colorectal cancer treated with fluorouracil-based chemotherapy. J Clin Oncol 24:5194–5200

    Article  CAS  PubMed  Google Scholar 

  69. Rossi A, Rosati G, Colarusso D, Manzione L (2003) Subcutaneous granulocyte-macrophage colony-stimulating factor in mucositis induced by an adjuvant 5-fluorouracil plus leucovorin regimen. A phase II study and review of the literature Oncology 64:353–360

    PubMed  Google Scholar 

  70. Rosso M, Blasi G, Gherlone E, Rosso R (1997) Effect of granulocyte-macrophage colony-stimulating factor on prevention of mucositis in head and neck cancer patients treated with chemo-radiotherapy. J Chemother 9:382–385

    Article  CAS  PubMed  Google Scholar 

  71. Rovirosa A, Ferre J, Biete A (1998) Granulocyte macrophage-colony-stimulating factor mouthwashes heal oral ulcers during head and neck radiotherapy. Int J Radiat Oncol Biol Phys 41:747–754

    Article  CAS  PubMed  Google Scholar 

  72. Ryu JK, Swann S, LeVeque F, Scarantino CW, Johnson D, Chen A, Fortin A, Pollock J, Kim H, Ang KK (2007) The impact of concurrent granulocyte macrophage-colony stimulating factor on radiation-induced mucositis in head and neck cancer patients: a double-blind placebo-controlled prospective phase III study by Radiation Therapy Oncology Group 9901. Int J Radiat Oncol Biol Phys 67:643–650

    Article  CAS  PubMed  Google Scholar 

  73. Rzepecki P, Sarosiek T, Barzal J, Oborska S, Nurzynski P, Wasko A, Szczylik C (2007) Palifermin for prevention of oral mucositis after haematopoietic stem cell transplantation- single centre experience. J BUON 12:477–482

    CAS  PubMed  Google Scholar 

  74. Saarilahti K, Kajanti M, Joensuu T, Kouri M, Joensuu H (2002) Comparison of granulocyte-macrophage colony-stimulating factor and sucralfate mouthwashes in the prevention of radiation-induced mucositis: a double-blind prospective randomized phase III study. Int J Radiat Oncol Biol Phys 54:479–485

    Article  CAS  PubMed  Google Scholar 

  75. Saber W, Zhang M-J, Steinert P, Chen M, Horowitz MM (2016) The impact of palifermin use on hematopoietic cell transplant outcomes in children. Biology of Blood and Marrow Transplantation 22:1460–1466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Sakellari I, Angelopoulou M, Tsopra O, Dervenoulas I, Tsirigotis P, Spyridonidis A, Liga M, Tsionos K, Anargyrou K, Pouli A Anagnostopoulos A (2015) A prospective study of incidence, clinical and quality of life consequences of oral mucositis post palifermin prophylaxis in patients undergoing high-dose chemotherapy and autologous hematopoietic cell transplantation. Ann Hematol 94:1733–1740

    Article  CAS  PubMed  Google Scholar 

  77. Schmidt E, Thoennissen N, Rudat A, Bieker R, Schliemann C, Mesters R, Zühlsdorf M, Müller-Tidow C, Berdel WJAoo (2008) Use of palifermin for the prevention of high-dose methotrexate-induced oral mucositis. 19:1644–1649

  78. Schneider SB, Nishimura RD, Zimmerman RP, Tran L, Shiplacoff J, Tormey M, Contreras R, Juillard GF (1999) Filgrastim (r-metHuG-CSF) and its potential use in the reduction of radiation-induced oropharyngeal mucositis: an interim look at a randomized, double-blind, placebo-controlled trial Cytokines. Cell Mol Ther 5:175–180

    CAS  Google Scholar 

  79. Schuster MW, Shore TB, Harpel JG, Greenberg J, Jalilizeinali B, Possley S, Gerwien RW, Hahne W, Halvorsen Y-DC (2008) Safety and tolerability of velafermin (CG53135-05) in patients receiving high-dose chemotherapy and autologous peripheral blood stem cell transplant. Supportive Care in Cancer 16:477–483

    Article  PubMed  Google Scholar 

  80. Somerfield M, Padberg J, Pfister D, Bennett C, Recht A, Smith T, Weeks J, Winn R, Durant J (2000) ASCO clinical practice guidelines: process, progress, pitfalls, and prospects. Class Pap Curr Comments 4:881–886

    Google Scholar 

  81. Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, Bekele BN, Raber-Durlacher J, Donnelly JP, Rubenstein EB (2004) Perspectives on cancer therapy-induced mucosal injury. Cancer 100:1995–2025

    Article  PubMed  Google Scholar 

  82. Spielberger R, Stiff P, Bensinger W, Gentile T, Weisdorf D, Kewalramani T, Shea T, Yanovich S, Hansen K, Noga S, McCarty J, LeMaistre CF, Sung EC, Blazar BR, Elhardt D, Chen MG, Emmanouilides C (2004) Palifermin for oral mucositis after intensive therapy for hematologic cancers. The New England journal of medicine 351:2590–2598

    Article  CAS  PubMed  Google Scholar 

  83. Sprinzl GM, Galvan O, de Vries A, Ulmer H, Gunkel AR, Lukas P, Thumfart WF (2001) Local application of granulocyte-macrophage colony stimulating factor (GM-CSF) for the treatment of oral mucositis. Eur J Cancer 37:2003–2009

    Article  CAS  PubMed  Google Scholar 

  84. Stiff PJ, Emmanouilides C, Bensinger WI, Gentile T, Blazar B, Shea TC, Lu J, Isitt J, Cesano A, Spielberger R (2006) Palifermin reduces patient-reported mouth and throat soreness and improves patient functioning in the hematopoietic stem-cell transplantation setting. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 24:5186–5193

    Article  CAS  Google Scholar 

  85. Straka C, Sandherr M, Salwender H, Wandt H, Metzner B, Hubel K, Silling G, Hentrich M, Franke D, Schwerdtfeger R, Freund M, Sezer O, Giagounidis A, Ehninger G, Grimminger W, Engert A, Schlimok G, Scheid C, Hellmann P, Heinisch H, Einsele H, Hinke A, Emmerich B (2011) Testing G-CSF responsiveness predicts the individual susceptibility to infection and consecutive treatment in recipients of high-dose chemotherapy. Blood 117:2121–2128

    Article  CAS  PubMed  Google Scholar 

  86. Su YB, Vickers AJ, Zelefsky MJ, Kraus DH, Shaha AR, Shah JP, Serio AM, Harrison LB, Bosl GJ, Pfister DG (2006) Double-blind, placebo-controlled, randomized trial of granulocyte-colony stimulating factor during postoperative radiotherapy for squamous head and neck cancer. Cancer J 12:182–188

    Article  CAS  PubMed  Google Scholar 

  87. Tsirigotis P, Triantafyllou K, Girkas K, Giannopoulou V, Ioannidou E, Chondropoulos S, Kalli T, Papaxoinis G, Pappa V, Papageorgiou E, Economopoulos T, Ladas SD, Dervenoulas J (2008) Keratinocyte growth factor is effective in the prevention of intestinal mucositis in patients with hematological malignancies treated with high-dose chemotherapy and autologous hematopoietic SCT: a video-capsule endoscopy study. Bone Marrow Transplant 42:337–343

    Article  CAS  PubMed  Google Scholar 

  88. Palifermin FDA approval. Accessed 28 July 2019, from https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/palifermin-marketed-kepivance.

  89. Palifermin FDA approval. Accessed 28 July 2019, from https://www.cancer.gov/about-cancer/treatment/drugs/palifermin.

  90. Vadhan-Raj S, Trent J, Patel S, Zhou X, Johnson MM, Araujo D, Ludwig JA, O'roark S, Gillenwater AM, Bueso-Ramos C (2010) Single-dose palifermin prevents severe oral mucositis during multicycle chemotherapy in patients with cancer: a randomized trial. Ann Intern Med 153:358–367

    Article  PubMed  Google Scholar 

  91. Valcarcel D, Sanz MA Jr, Sureda A, Sala M, Munoz L, Subira M, Laborda R, Clopes A, Sierra J (2002) Mouth-washings with recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) do not improve grade III-IV oropharyngeal mucositis (OM) in patients with hematological malignancies undergoing stem cell transplantation. Results of a randomized double-blind placebo-controlled study Bone marrow transplantation 29:783–787

    Article  CAS  PubMed  Google Scholar 

  92. van der Lelie H, Thomas BL, van Oers RH, Ek-Post M, Sjamsoedin SA, van Dijk-Overtoom ML, Timmer JG, von dem Borne AE (2001) Effect of locally applied GM-CSF on oral mucositis after stem cell transplantation: a prospective placebo-controlled double-blind study. Ann Hematol 80:150–154

    Article  PubMed  Google Scholar 

  93. Verhagen M, Wondergem M, Visser O (2009) Palifermin dose should be adjusted to different therapy regimens. Bone Marrow Transplant 43:665

    Article  CAS  PubMed  Google Scholar 

  94. Viens P, Gravis G, Bladou F, Lechevallier E, Baume D, Camerlo J, Cowen D, Coulange C, Serment G, Resbeut M, Maraninchi D (1996) Impact of recombinant human granulocyte colony stimulating factor on dose intensity and toxicity of three cycles of methotrexate, vinblastine, doxorubicin and cisplatin in patients with previously untreated urothelial bladder carcinoma. Eur Cytokine Netw 7:395–399

    CAS  PubMed  Google Scholar 

  95. Vitale KM, Violago L, Cofnas P, Bishop J, Jin Z, Bhatia M, Kung AL, George D, Garvin J, Satwani P (2014) Impact of palifermin on incidence of oral mucositis and healthcare utilization in children undergoing autologous hematopoietic stem cell transplantation for malignant diseases. Pediatr Transplant 18:211–216

    Article  CAS  PubMed  Google Scholar 

  96. Wagner W, Alfrink M, Haus U, Matt J (1999) Treatment of irradiation-induced mucositis with growth factors (rhGM-CSF) in patients with head and neck cancer. Anticancer Res 19:799–803

    CAS  PubMed  Google Scholar 

  97. Wang L, Huang X-E, Ji Z-Q, Liu M-Y, Qian T, Li L (2016) Safety and efficacy of a mouth-rinse with granulocyte colony stimulating factor in patients with chemotherapy-induced oral mucositis. Asian Pacific Journal of Cancer Prevention 17:413–418

    Article  PubMed  Google Scholar 

  98. Wu HG, Song SY, Kim YS, Oh YT, Lee CG, Keum KC, Ahn YC, Lee SW (2009) Therapeutic effect of recombinant human epidermal growth factor (RhEGF) on mucositis in patients undergoing radiotherapy, with or without chemotherapy, for head and neck cancer: a double-blind placebo-controlled prospective phase 2 multi-institutional clinical trial. Cancer 115:3699–3708

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors are thankful for the medical librarians for their valuable contribution to this project: Lorraine Porcello, MSLIS, MSIM—Bibby Dental Library, Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY, USA; Daniel A. Castillo, MLIS—Edward G. Miner Library, University of Rochester Medical Center, Rochester, NY, USA.

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Authors and Affiliations

  1. Adelaide Dental School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, 5005, South Australia, Australia

    Richard M. Logan & Abdul Rahman Al-Azri

  2. Dental and OMFS Department, Oral Pathology and Medicine, Al-Nahdha Hospital, Ministry of Health, Muscat, Oman

    Abdul Rahman Al-Azri

  3. Medical Oncology, University of Brescia, ASST-Spedali Civili, Brescia, Italy

    Paolo Bossi

  4. School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia

    Andrea M. Stringer

  5. Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, 5005, South Australia, Australia

    Andrea M. Stringer

  6. Clinical Pharmacy, Cancer Treatment Centers of America, Boca Raton, FL, USA

    Jamie K. Joy

  7. Okayama University Hospital, 2-5-1, Shikata-cho, Kita-ku, Okayama, Japan

    Yoshihiko Soga

  8. Department of Oral and Maxillofacial Surgery, The Mount Sinai Hospital, New York, NY, USA

    Vinisha Ranna

  9. Oral Medicine, Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY, USA

    Anusha Vaddi & Sharon Elad

  10. Division of Oral and Maxillofacial Diagnostic Sciences, University of Connecticut School of Dental Medicine, Farmington, CT, USA

    Anusha Vaddi & Rajesh V. Lalla

  11. Department of Oral Medicine, Academic Centre for Dentistry Amsterdam, University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, Netherlands

    Judith E. Raber-Durlacher

  12. Department of Oral and Maxillofacial Surgery, Amsterdam UMC, University of Amsterdam , Amsterdam, Netherlands

    Judith E. Raber-Durlacher

  13. Alice Lee Centre for Nursing Studies, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Karis Kin Fong Cheng

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  1. Richard M. Logan
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  2. Abdul Rahman Al-Azri
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Consortia

On behalf of the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO)

Corresponding author

Correspondence to Abdul Rahman Al-Azri.

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Conflict of interest

Per MASCC Guidelines Policy, employees of commercial entities were not eligible to serve on this MASCC Guidelines Panel. PB has served an advisory role for AstraZeneca, Helsinn, and Kyowa Kyrin and received grants from Merck, Kyowa Kyrin, and Roche. RVL has served as a consultant for Alira Health, Colgate Oral Pharmaceuticals, Galera Therapeutics, Ingalfarma SA, Monopar Therapeutics, Mundipharma, and Sucampo Pharma; has received research support to his institution from Galera Therapeutics, Novartis, Oragenics, and Sucampo Pharma; and has received stock in Logic Biosciences. SE Discloses no conflict of interest in regards to the subject matter, and serve as a consultant for Falk Pharma outside the submitted work.

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Logan, R.M., Al-Azri, A.R., Bossi, P. et al. Systematic review of growth factors and cytokines for the management of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer 28, 2485–2498 (2020). https://doi.org/10.1007/s00520-019-05170-9

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