Skip to main content

Advertisement

SpringerLink
Log in

Growth factors and cytokines in the prevention and treatment of oral and gastrointestinal mucositis

  • Review Article
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript

Abstract

Goals of work

Growth factors and cytokines may be useful in preventing chemotherapy (CT)- and radiotherapy (RT)-induced oral and gastrointestinal mucositis. Two systematic reviews of the medical literature on growth factors and cytokines for the amelioration of CT- and RT-induced mucositis throughout the alimentary tract were performed by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology. The aim of these evidence-based scientific reviews was to critically evaluate the literature and create evidence-based guidelines for the use of growth factors and cytokines in the prevention or treatment of CT- and RT-induced mucositis.

Method

The two reviews covered articles on clinical trials from January 1966 through May 2002 and preclinical studies from June 2002 through May 2005, respectively. The systematic review process was based on a well-established method for evaluating scientific literature.

Main results

The number of articles in the first review was 29. In the second review, 23 articles were evaluated, 14 preclinical and 9 clinical studies. It was concluded from the first review that there was no sufficient evidence to provide any recommendations for clinical practice guidelines regarding growth factors and cytokines. From the second review, a guideline could be presented recommending the use of recombinant human keratinocyte growth factor-1 (palifermin) to prevent oral mucositis in patients receiving high-dose CT and total body irradiation followed by stem cell transplantation for haematological malignancies. A guideline could also be provided suggesting that granulocyte macrophage colony-stimulating factor mouthwash not be used for the prevention of oral mucositis in the transplant setting with high-dose CT and autologous or allogeneic stem cell transplantation.

Conclusions

These systematic reviews have provided clarity and shown exciting new results. Further studies will provide new options for this debilitating side-effect of cancer therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Abitbol AA, Sridhar K, Lewin A, Schawde J, Raub W, Wolfson A, Gonzalez-Angulo C, Adessa A, Goodwin J, Markoe A (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  PubMed  CAS  Google Scholar 

  2. Alderson R, Gohari-Fritsch S, Olsen H, Roschke V, Vance C, Connolly K (2002) In vitro and in vivo effects of repifermin (keratinocyte growth factor-2, KGF-2) on human carcinoma cells. Cancer Chemother Pharmacol 50:202–212

    Article  PubMed  CAS  Google Scholar 

  3. Alvarez E, Fey EG, Valaz P, Yim Z, Peterson JD, Mesri M, Jeffers M, Dindinger M, Twomlow, Ghatpande A, LaRochelle WJ, Sonis ST, Lichtenstien H (2003) Preclinical characterization of CG53135 (FGF-20) in radiation and concomitant chemotherapy/radiation-induced oral mucositis. Clin Cancer Res 9:3454–3461

    PubMed  CAS  Google Scholar 

  4. Antin JH, Lee SJ, Neuberg D, Alyea E, Soiffer RJ, Sonis S, Ferrara JLM (2002) A phase I/II double-blind, placebo-controlled study of recombinant human interleukin-11 for mucositis and acute GVHD prevention in allogeneic stem cell transplantation. Bone Marrow Transplant 29:373–377

    Article  PubMed  CAS  Google Scholar 

  5. 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 88:311–315

    CAS  Google Scholar 

  6. Booth C, Booth D, Williamson S, Demchyshyn LL, Potten CS (2004) Teduglutide (Gly2GLP-2) protects small intestinal stem cells from radiation damage. Cell Prolif 37:385–400

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  8. Chi K-H, Chen C-H, Chan W-K, Chow K-C, Chen S-Y, Yen S-H, Chao JY, Chang C-Y, 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. J Clin Oncol 13:2620–2628

    PubMed  CAS  Google Scholar 

  9. Clarke J, Butler R, Howarth G, Read L, Regester G (2002) Exposure of oral mucosa to bioactive milk factors reduces severity of chemotherapy-induced mucositis in the hamster. Oral Oncol 38:478–485

    Article  PubMed  CAS  Google Scholar 

  10. Cool JC, Dyer JL, Xian CJ, Butler RN, Geier MS, Howarth GS (2005) Pre-treatment with insulin-like growth factor-1 partially ameliorates 5-fluorouracil-induced intestinal mucositis in rats. Growth Horm IGF Res 15:72–82

    Article  PubMed  CAS  Google Scholar 

  11. Crawford J, Tomita D, 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

    PubMed  CAS  Google Scholar 

  12. 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  PubMed  CAS  Google Scholar 

  13. De la Torro A, Reguiero CA, Valcarcel FJ (1997) Granulocyte-macrophage colony-stimulating factor mouthwashes improve radiation induced mucositis in AIDS patients. Letter to the editor. Radiother Oncol 43:229–230

    Article  Google Scholar 

  14. Dumbrigue HB, Sandow P, Nguyen K-H, Humphreys-Beher M (2000) Salivary epidermal growth factor levels decrease in patients receiving radiation therapy to the head and neck. Oral Surg Oral Med Oral Pathol 89:710–716

    CAS  Google Scholar 

  15. Dörr W, Spekl K, Farrell CL (2002) The effect of keratinocyte growth factor on healing of manifest radiation ulcers in mouse tongue epithelium. Cell Prolif 35(Suppl 1):86–92

    Article  PubMed  Google Scholar 

  16. Dörr W, Spekl K, Farrell CL (2002) Amelioration of acute oral mucositis by keratinocyte growth factor: fractionated irradiation. Int J Radiat Oncol Biol Phys 54:245–251

    PubMed  Google Scholar 

  17. Epstein JB, Emerton S, Guglietta A, Le N (1997) Assessment of epidermal growth factor in oral secretions of patients receiving radiation therapy for cancer. Oral Oncol 33:359–363

    Article  PubMed  CAS  Google Scholar 

  18. Epstein JB, Gorsky M, Guglietta A, Le N, Sonis ST (2000) The correlation between epidermal growth factor levels in saliva and the severity of oral mucositis during oropharyngeal radiation therapy. Cancer 89:2258–2265

    Article  PubMed  CAS  Google Scholar 

  19. Farrell CL, Bready JV, Rex KL, Chen JN, DiPalma CR, Whitcomb KL, Yin S, Hill DC, Wiemann B, Starnes CO, Havill AM, Lu ZN, Aukerman SL, Pierce GF, Thomason A, Potten CS, Ulich TR, Lacey DL (1998) Keratinocyte growth factor protects mice from chemotherapy and radiation-induced gastrointestinal injury and mortality. Cancer Res 58:933–939

    PubMed  CAS  Google Scholar 

  20. Farrell CL, Rex KL, Chen JN, Bready JV, DiPalma CR, Kaufman SA, Rattan A, Scully S, Lacey DL (2002) The effects of keratinocyte growth factor in preclinical models of mucositis. Cell Prolif 35(Suppl 1):78–85

    Article  PubMed  CAS  Google Scholar 

  21. Feliciani C, Gupta AK, Sauder DN (1996) Keratinocytes and cytokine/growth factors. Crit Rev Oral Biol Med 7:300–318

    Article  PubMed  CAS  Google Scholar 

  22. Foncuberta MC, Cagnoni PJ, Brandts CH, Mandanas R, Fields K, Derigs HG, Reed E, Sonis ST, Fay J, LeVeque F, Pouillart P, Schrezenmeier H, Emmons R, Thiel E (2001) Topical transforming growth factor-β3 in the prevention or alleviation of chemotherapy-induced oral mucositis in patients with lymphomas or solid tumors. J Immunother 24:384–388

    Article  PubMed  CAS  Google Scholar 

  23. Freytes CO, Ratanatharathorn V, Taylor C, Abbout 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 hematopoietic stem cell transplantation. Clin Cancer Res 10:8318–8324

    Article  PubMed  CAS  Google Scholar 

  24. Gabrilove JL, Jakubowski A, Scher H, Sterberg C, Wong G, Grous J, Yagodo A, Fain K, Moore M, Clarkson B, Oettgen H, Alton K, Welte K, Souza L (1988) Effect of granulocyte colony-stimulating factor on neutropenia and associated morbidity due to chemotherapy for transitional-cell carcinoma of the urothelium. N Engl J Med 318:1414–1422

    Article  PubMed  CAS  Google Scholar 

  25. Gibson RJ, Keefe D, Thompson FM, Clarke JM, Goland GJ, Cummins AG (2002) Effect of interleukin-11 on ameliorating intestinal damage after methotrexate treatment of breast cancer in rats. Dig Dis Sci 47:2751–2757

    Article  PubMed  CAS  Google Scholar 

  26. Gibson RJ, Keefe DMK, Clarke JM, Regester GO, Thompson FM, Goland GJ, Edwards BG, Cummins AG (2002) The effect of keratinocyte growth factor on tumour growth and small intestinal mucositis after chemotherapy in the rat with breast cancer. Cancer Chemother Pharmacol 50:53–58

    Article  PubMed  CAS  Google Scholar 

  27. Gibson RJ, Bowen JM, Keefe DMK (2005) Palifermin reduces diarrhea and increases survival following irinotecan treatment in tumor-bearing DA rats. Int J Cancer 116:464–470

    Article  PubMed  CAS  Google Scholar 

  28. Goa KL, Bryson HM (1994) Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF): an appraisal of its pharmacoeconomic status in neutropenia associated with chemotherapy and autologous bone marrow transplant. Pharmacoeconomics 5:56–77

    Article  PubMed  CAS  Google Scholar 

  29. Goldsby RA, Kindt TJ, Osborne BA (2000) Kuby immunology, 4th edn. WH Freeman, New York

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  31. 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  PubMed  CAS  Google Scholar 

  32. Hejna M, Köstler 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. Eur J Cancer 37:1994–2002

    Article  PubMed  CAS  Google Scholar 

  33. Hesketh R (1997) The oncogene and tumour suppressor gene, 2nd edn. Academic/Harcourt Brace, London

    Google Scholar 

  34. Howarth GS, Francis GL, Cool JC, Xu X, Byard RW, Read LC (1996) Milk growth factors enriched from cheese whey ameliorate intestinal damage by methotrexate when administered orally to rats. J Nutr 126:2519–2530

    PubMed  CAS  Google Scholar 

  35. 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  PubMed  CAS  Google Scholar 

  36. Ino M, Ushiro K, Ino C, Yamashita T, Kumazawa T (1993) Kinetics of epidermal growth factor in saliva. Acta Otolaryngol S500:126–130

    Article  Google Scholar 

  37. Jones CA, Shaw PJ, Stevens MM (1999) Use of granulocyte colony stimulating factor to reduce the toxicity of super-VAC chemotherapy in advanced solid tumours in childhood. Med Pediatr Oncol 25:84–89

    Article  Google Scholar 

  38. Kannan V, Bapsy P, 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 5:1005–1010

    Google Scholar 

  39. Kanz L, Lindemann A, Oster W, Herrmann F, Mertelsmann R (1991) Hemopoietins in clinical oncology. Am J Clin Oncol S14:S27–S33

    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  PubMed  CAS  Google Scholar 

  41. Kaye A (1996) Clinical development of recombinant human interleukin-11 to treat chemotherapy-induced thrombocytopenia. Curr Opin Hematol 3:209–215

    Article  PubMed  CAS  Google Scholar 

  42. Keith JC Jr, Albert L, Sonis ST, Pfeiffer CJ, Schaub RG (1994) IL-11, a pleiotrophic cytokine: exciting new effects of IL-11 on gastrointestinal mucosal biology. Stem Cells 12(Suppl):79–90

    PubMed  Google Scholar 

  43. Knox JJ, Puodziunas AL, Feld R (2000) Chemotherapy-induced oral mucositis, prevention and management. Drugs Aging 17:257–267

    Article  PubMed  CAS  Google Scholar 

  44. Lieschke GJ, Ramenghi U, O’Connor MP, Sheridan W, Szer J, Morstyn G (1992) Studies of oral neutrophil levels in patients receiving G-CSF after autologous marrow transplantation. Br J Haematol 82:589–595

    Article  PubMed  CAS  Google Scholar 

  45. Lockhart PB, Sonis ST (1979) Relationships of oral complications to peripheral blood leukocyte and platelet counts in patients receiving cancer chemotherapy. Oral Surg 48:21–28

    Article  CAS  PubMed  Google Scholar 

  46. 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 randomised study. Int J Radiat Oncol Biol Phys 46:525–534

    PubMed  CAS  Google Scholar 

  47. 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 chemo-radiotherapy-induced severe oral mucositis in advanced head and neck cancer patients: an evaluation of effectiveness, safety and costs. Oncol Rep 10:197–206

    PubMed  CAS  Google Scholar 

  48. Mascarin M, Franchin G, Minatel E, Gobitti C, Talamini R, de Maria D, Trovo M (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  PubMed  CAS  Google Scholar 

  49. Meropol NJ, Somer RA, Gutheil J, Pelley RJ, Modiano MR, Rowinsky EK, Rothenberg ML, Redding SW, Serdar CM, Yao B, Heard R, Rosen LS (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  PubMed  CAS  Google Scholar 

  50. 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 study. Int J Radiat Oncol Biol Phys 42:551–556

    PubMed  CAS  Google Scholar 

  51. Nicolatou-Galitis O, Dardoufas K, Markoulatos P, Sotiropoulou-Lontou A, Kyprianou K, Kolitsi G, Pissakas G, Skarleas C, Kouloullas V, Papanicolaou V, Legakis NJ, Velegraki A (2001) Oral pseudomembranous candidiasis, herpes simplex virus-1 infection, and oral mucositis in head and neck cancer patients receiving radiotherapy and granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwash. J Oral Pathol Med 30:471–480

    Article  PubMed  CAS  Google Scholar 

  52. Prince HM, Regester G, Gates P, Jablonskis L, Seymour JF, Lillie K, West R, Wolf M, Januszewicz H, Belford D (2005) A phase Ib clinical trial of PV701, a milk-derived protein extract, for the prevention and treatment of oral mucositis in patients undergoing high-dose BEAM chemotherapy. Biol Blood Marrow Transplant 11:512–520

    Article  PubMed  CAS  Google Scholar 

  53. 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. Oncology 64:353–360

    Article  PubMed  Google Scholar 

  54. 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

    PubMed  CAS  Google Scholar 

  55. 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

    PubMed  CAS  Google Scholar 

  56. Rubenstein EB, Peterson DE, Schubert M, Keefe D, McGuire D, Epstein J, Elting LS, Fox PC, Cooksley C, Sonis ST (2004) Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer 100(Suppl):2026–2046

    Article  PubMed  Google Scholar 

  57. Somerfield MR, Padberg JJ, Pfister DG, Bennett CL, Recht A, Smith TJ, Weeks JC, Winn RJ, Durant JR (2000) ASCO clinical practice guidelines: process, progress, pitfalls, and prospects. Class Pap Curr Comments 4:881–886

    Google Scholar 

  58. 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: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer 100(Suppl):1995–2025

    Article  PubMed  Google Scholar 

  59. Sonis ST, Peterson RL, Edwards LJ, Lucey CA, Wang L, Mason L, Login G, Ymamkawa M, Moses G, Bouchard P, Hayes LL, Bedrosian C, Dorner AJ (2000) Defining mechanisms of action of interleukin-11 on the progression of radiation-induced oral mucositis in hamsters. Oral Oncol 36:373–381

    Article  PubMed  CAS  Google Scholar 

  60. Spielberger R, Stiff P, Bensinger W, Gentile T, Weisdorf D, Kewalramani T, Shea T, Yanovich S, Hansen K, Noga S, McCarty J, LeMaistre F, Sung EC, Blazar BR, Elhardt D, Chen MG, Emmanouilides C (2004) Palifermin for oral mucositis after intensive therapy for hematologic cancers. N Engl J Med 351:2590–2598

    Article  PubMed  CAS  Google Scholar 

  61. 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  PubMed  CAS  Google Scholar 

  62. Tran CD, Howarth GS, Coyle P, Philcox JC, Rofe AM, Butler RN (2003) Dietary supplementation with zinc and a growth factor extract derived from bovine cheese whey improves methotrexate-damaged rat intestine. Am J Clin Nutr 77:1296–1303

    PubMed  CAS  Google Scholar 

  63. Wagner W, Alfrink M, Haus U, Matt J (1999) Treatment of irradiation-induced mucositis with growth factors (shGM-CSF) in patients with head and neck cancer. Anticancer Res 19:799–804

    PubMed  CAS  Google Scholar 

  64. Valcárcel D, Sanz MA Jr, Sureda A, Sala M, Munoz L, Subirá M, Laborda R, Clopés 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 Transplant 29:783–787

    Article  PubMed  Google Scholar 

  65. Van der Lelie H, Thomas BLM, van Oers RHJ, Ek-Post M, Sjamsoedin SAS, van Dijk-Overtoom ML, Timmer JG, von dem Borne A (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 

  66. Van't Land B, van Beek NMA, van den Berg JJM, M'Rabet L (2004) Lactoferrin reduces methotrexate-induced small intestinal damage, possibly through inhibition of GLP-2-mediated epithelial cell proliferation. Dig Dis Sci 49:425–433

    Article  Google Scholar 

  67. Wardley AM, Jayson GC, Swindell R, Morgenstern GR, Chang J, Bloor R, Fraser CJ, Scarffe JH (2000) Prospective evaluation of oral mucositis in patients receiving myeloablative conditioning regimens and haemopoietic progenitor rescue. Br J Haematol 11:292–299

    Article  Google Scholar 

  68. Werner S (1998) Keratinocyte growth factor: a unique player in epithelial repair processes. Cytokine Growth Factor Rev 9:153–165

    Article  PubMed  CAS  Google Scholar 

  69. Wymenga AN, van der Graaf WT, Hofstra LS, Spijkervet FK, Timens W, Timmer-Bosscha H, Sluiter WJ, van Buuren AH, Mulder NH, de Vries EG (1999) Phase I study of transforming growth factor-β3 mouthwashes for prevention of chemotherapy-induced mucositis. Clin Cancer Res 5:1363–1368

    PubMed  CAS  Google Scholar 

  70. Zhao J, Huang L, Belmar N, Buelow R, Fong T (2004) Oral RDP58 allows CPT-11 dose intensification for enhanced tumor response by decreasing gastrointestinal toxicity. Clin Cancer Res 10:2851–2859

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Oral Medicine, Sahlgrenska Academy, Göteborg University, P.O. Box 450, 405 30, Göteborg, Sweden

    Inger von Bültzingslöwen

  2. Department of Oral Medicine, Carolinas Medical Center, Charlotte, NC, USA

    Michael T. Brennan

  3. Department of Oral and Maxillofacial Surgery, University Medical Center and University of Groningen, Groningen, The Netherlands

    Fred K. L. Spijkervet

  4. Department of Oral Pathology, Dental School, University of Adelaide, Adelaide, Australia

    Richard Logan

  5. Department of Medical Oncology, Royal Adelaide Hospital, Adelaide, Australia

    Andrea Stringer & Dorothy Keefe

  6. Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands

    Judith E. Raber-Durlacher

  7. Department of Periodontology, Academic Centre of Dentistry, Amsterdam, The Netherlands

    Judith E. Raber-Durlacher

Authors
  1. Inger von Bültzingslöwen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael T. Brennan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fred K. L. Spijkervet
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Richard Logan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andrea Stringer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Judith E. Raber-Durlacher
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dorothy Keefe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Inger von Bültzingslöwen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bültzingslöwen, I.v., Brennan, M.T., Spijkervet, F.K. et al. Growth factors and cytokines in the prevention and treatment of oral and gastrointestinal mucositis. Support Care Cancer 14, 519–527 (2006). https://doi.org/10.1007/s00520-006-0052-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-006-0052-7

Keywords

Search

Navigation