Oral Mucositis

  • Nathaniel Treister
  • Stephen Sonis*
Part of the Cancer Drug Discovery and Development book series (CDD&D)


Mucositis is a common, painful, treatment-disrupting toxicity of both radiotherapy and chemotherapy. Patients with cancers of the head and neck receiving radiation therapy with and without induction or concomitant chemotherapy, and individuals being treated with high-dose chemotherapy regimens are at particularly high risk. Importantly, even patients receiving conventional dosing schemes for other forms of cancer have a meaningful chance of developing painful lesions of the mouth and throat during their treatment. The fact that the pathobiology of mucositis is complex and multifaceted provides opportunities for mechanistically based interventions. While palifermin is the only agent currently approved for treatment, it also represents an example of other agents in development for which efficacy is based on disruption of the biological pathways leading to mucositis. This chapter discusses the clinical characteristics of mucositis, how it is evaluated and scored, its pathogenesis, and current and evolving prevention and treatment strategies.


Oral complications Mucosal injury Radiation therapy Cancer chemotherapy Oral disease Head and neck cancer Hematopoietic cell transplantation Introduction 


  1. 1.
    Sonis ST, Eilers JP, Epstein JB,. et al. 1999; Validation of a new scoring system for the assessment of clinical trial research of oral mucositis induced by radiation or chemotherapy. Mucositis Study Group. Cancer 85:2103–13PubMedCrossRefGoogle Scholar
  2. 2.
    McGuire DB, Peterson DE, Muller S, Owen DC, Slemmons MF, Schubert MM. 2002; The 20 item oral mucositis index: Reliability and validity in bone marrow and stem cell transplant patients. Cancer Invest 20:893–903PubMedCrossRefGoogle Scholar
  3. 3.
    Walsh LJ, Hill G, Seymour G, Roberts A. 1990; A scoring system for the quantitative evaluation of oral mucositis during bone marrow transplantation. Spec Care Dentist 10:190–5PubMedCrossRefGoogle Scholar
  4. 4.
    Eilers J. 2004; Nursing interventions and supportive care for the prevention and treatment of oral mucositis associated with cancer treatment. Oncol Nurs Forum 31:13–23PubMedCrossRefGoogle Scholar
  5. 5.
    Keefe DM, Schubert MM, Elting LS,. et al. 2007; Updated clinical practice guidelines for the prevention and treatment of mucositis. Cancer 109:820–31PubMedCrossRefGoogle Scholar
  6. 6.
    Elting LS, Cooksley CD, Chambers MS, Garden AS. 2007; Risk, outcomes, and costs of radiation-induced oral mucositis among patients with head-and-neck malignancies. Int J Radiat Oncol Biol Phys 68:1110–20PubMedCrossRefGoogle Scholar
  7. 7.
    Martin M, Pienkowski T, Mackey J,. et al. 2005; Adjuvant docetaxel for node-positive breast cancer. N Engl J Med 352:2302–13PubMedCrossRefGoogle Scholar
  8. 8.
    Abu-Khalaf MM, Windsor S, Ebisu K,. et al. 2005; Five-year update of an expanded phase II study of dose-dense and -intense doxorubicin, paclitaxel and cyclophosphamide (ATC) in high-risk breast cancer. Oncology 69:372–83PubMedCrossRefGoogle Scholar
  9. 9.
    Berruti A, Bitossi R, Bottini A,. et al. 2005; Combination regimen of epirubicin, vinorelbine and 5-fluorouracil continuous infusion as first-line chemotherapy in anthracycline-naive metastatic breast cancer patients. Eur J Cancer 41:249–55PubMedCrossRefGoogle Scholar
  10. 10.
    Coleman RE, Biganzoli L, Canney P,. et al. 2006; A randomised phase II study of two different schedules of pegylated liposomal doxorubicin in metastatic breast cancer (EORTC-10993). Eur J Cancer 42:882–7PubMedCrossRefGoogle Scholar
  11. 11.
    Savio G, Laudani A, Leonardi V,. et al. 2006; Treatment of metastatic breast cancer with vinorelbine and docetaxel. Am J Clin Oncol 29:276–80PubMedCrossRefGoogle Scholar
  12. 12.
    Jones SE, Savin MA, Holmes FA,. et al. 2006; Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol 24:5381–7PubMedCrossRefGoogle Scholar
  13. 13.
    Barasch A, Peterson DE. 2003; Risk factors for ulcerative oral mucositis in cancer patients: Unanswered questions. Oral Oncol 39:91–100PubMedCrossRefGoogle Scholar
  14. 14.
    Sonis ST, Elting LS, Keefe D,. et al. 2004; Perspectives on cancer therapy-induced mucosal injury: Pathogenesis, measurement, epidemiology, and consequences for patients. Cancer 100:1995–2025PubMedCrossRefGoogle Scholar
  15. 15.
    Sonis ST, Oster G, Fuchs H,. et al. 2001; Oral mucositis and the clinical and economic outcomes of hematopoietic stem-cell transplantation. J Clin Oncol 19:2201–5PubMedGoogle Scholar
  16. 16.
    Elting LS, Cooksley C, Chambers M, Cantor SB, Manzullo E, Rubenstein EB. 2003; The burdens of cancer therapy. Clinical and economic outcomes of chemotherapy-induced mucositis. Cancer 98:1531–9PubMedCrossRefGoogle Scholar
  17. 17.
    Ruescher TJ, Sodeifi A, Scrivani SJ, Kaban LB, Sonis ST. 1998; The impact of mucositis on alpha-hemolytic streptococcal infection in patients undergoing autologous bone marrow transplantation for hematologic malignancies. Cancer 82:2275–81PubMedCrossRefGoogle Scholar
  18. 18.
    Vera-Llonch M, Oster G, Hagiwara M, Sonis S. 2006; Oral mucositis in patients undergoing radiation treatment for head and neck carcinoma. Cancer 106:329–36PubMedCrossRefGoogle Scholar
  19. 19.
    Trotti A, Bellm LA, Epstein JB,. et al. 2003; 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 66:253–62PubMedCrossRefGoogle Scholar
  20. 20.
    Keefe DM,. et al. 2007; Oral mucositis is associated with increased resource use among patients receiving treatment for cancers of the head and neck. ASCO abstract# 31629 25:6070Google Scholar
  21. 21.
    Sonis ST. 1998; Mucositis as a biological process: A new hypothesis for the development of chemotherapy-induced stomatotoxicity. Oral Oncol 34:39–43PubMedCrossRefGoogle Scholar
  22. 22.
    Sonis ST. 2004; The pathobiology of mucositis. Nat Rev Cancer 4:277–84PubMedCrossRefGoogle Scholar
  23. 23.
    Sonis ST. 2002; The biologic role for nuclear factor-kappaB in disease and its potential involvement in mucosal injury associated with anti-neoplastic therapy. Crit Rev Oral Biol Med 13:380–9PubMedCrossRefGoogle Scholar
  24. 24.
    Logan RM, Gibson RJ, Sonis ST, Keefe DM. 2007; Nuclear factor-kappaB (NF-kappaB) and cyclooxygenase-2 (COX-2) expression in the oral mucosa following cancer chemotherapy. Oral Oncol 43:395–401PubMedCrossRefGoogle Scholar
  25. 25.
    Lima V, Brito GA, Cunha FQ,. et al. 2005; Effects of the tumour necrosis factor-alpha inhibitors pentoxifylline and thalidomide in short-term experimental oral mucositis in hamsters. Eur J Oral Sci 113:210–7PubMedCrossRefGoogle Scholar
  26. 26.
    Hwang D, Popat R, Bragdon C, O’Donnell KE, Sonis ST. 2005; Effects of ceramide inhibition on experimental radiation-induced oral mucositis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 100:321–9PubMedCrossRefGoogle Scholar
  27. 27.
    de Koning BA, Lindenbergh-Kortleve DJ, Pieters R, Buller HA, Renes IB, Einerhand AW. Alterations in epithelial and mesenchymal intestinal gene expression during doxorubicin-induced mucositis in mice. Dig Dis Sci 2007Google Scholar
  28. 28.
    Sonis S, Haddad R, Posner M,. et al. 2007; Gene expression changes in peripheral blood cells provide insight into the biological mechanisms associated with regimen-related toxicities in patients being treated for head and neck cancers. Oral Oncol 43:289–300PubMedCrossRefGoogle Scholar
  29. 29.
    Lark RL, McNeil SA, VanderHyde K, Noorani Z, Uberti J, Chenoweth C. 2001; Risk factors for anaerobic bloodstream infections in bone marrow transplant recipients. Clin Infect Dis 33:338–43PubMedCrossRefGoogle Scholar
  30. 30.
    Keefe DM, Peterson DE, Schubert MM. 2006; Developing evidence-based guidelines for management of alimentary mucositis: Process and pitfalls. Support Care Cancer 14:492–8PubMedCrossRefGoogle Scholar
  31. 31.
    Worthington HV, Clarkson JE, Eden OB. Interventions for preventing oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev 2006:CD000978Google Scholar
  32. 32.
    Bensadoun RJ, Schubert MM, Lalla RV, Keefe D. 2006; Amifostine in the management of radiation-induced and chemo-induced mucositis. Support Care Cancer 14:566–72PubMedCrossRefGoogle Scholar
  33. 33.
    Spielberger R, Stiff P, Bensinger W,. et al. 2004; Palifermin for oral mucositis after intensive therapy for hematologic cancers. N Engl J Med 351:2590–8PubMedCrossRefGoogle Scholar
  34. 34.
    Blijlevens N, Sonis S. 2007; Palifermin (recombinant keratinocyte growth factor-1): A pleiotropic growth factor with multiple biological activities in preventing chemotherapy- and radiotherapy-induced mucositis. Ann Oncol 18:817–26PubMedCrossRefGoogle Scholar
  35. 35.
    Rosen LS, Abdi E, Davis ID,. et al. 2006; Palifermin reduces the incidence of oral mucositis in patients with metastatic colorectal cancer treated with fluorouracil-based chemotherapy. J Clin Oncol 24:5194–200PubMedCrossRefGoogle Scholar
  36. 36. von
    Bultzingslowen I, Brennan MT, Spijkervet FK,. et al. 2006; Growth factors and cytokines in the prevention and treatment of oral and gastrointestinal mucositis. Support Care Cancer 14:519–27CrossRefGoogle Scholar
  37. 37.
    Epstein JB, Silverman S, JrPaggiarino, DA et al. 2001; Benzydamine HCl for prophylaxis of radiation-induced oral mucositis: Results from a multicenter, randomized, double-blind, placebo-controlled clinical trial. Cancer 92:875–85PubMedCrossRefGoogle Scholar
  38. 38.
    Ship JA, Eisbruch A, D’Hondt E, Jones RE. 1997; Parotid sparing study in head and neck cancer patients receiving bilateral radiation therapy: One-year results. J Dent Res 76:807–13PubMedCrossRefGoogle Scholar
  39. 39.
    Perch SJ, Machtay M, Markiewicz DA, Kligerman MM. 1995; Decreased acute toxicity by using midline mucosa-sparing blocks during radiation therapy for carcinoma of the oral cavity, oropharynx, and nasopharynx. Radiology 197:863–6PubMedGoogle Scholar
  40. 40.
    Farahani M, Eichmiller FC, McLaughlin WL. 1990; Measurement of absorbed doses near metal and dental material interfaces irradiated by X- and gamma-ray therapy beams. Phys Med Biol 35:369–85PubMedCrossRefGoogle Scholar
  41. 41.
    Reitemeier B, Reitemeier G, Schmidt A,. et al. 2002; Evaluation of a device for attenuation of electron release from dental restorations in a therapeutic radiation field. J Prosthet Dent 87:323–7PubMedCrossRefGoogle Scholar
  42. 42.
    Rocke LK, Loprinzi CL, Lee JK,. et al. 1993; A randomized clinical trial of two different durations of oral cryotherapy for prevention of 5-fluorouracil-related stomatitis. Cancer 72:2234–8PubMedCrossRefGoogle Scholar
  43. 43.
    Bensadoun RJ. 2002; Low level laser therapy: A real hope in the management of chemo-induced and radiation-induced mucositis? Cancer J 8:236–8PubMedCrossRefGoogle Scholar
  44. 44.
    Migliorati CA, Oberle-Edwards L, Schubert M. 2006; The role of alternative and natural agents, cryotherapy, and/or laser for management of alimentary mucositis. Support Care Cancer 14:533–40PubMedCrossRefGoogle Scholar
  45. 45.
    Desmet KD, Paz DA, Corry JJ,. et al. 2006; Clinical and experimental applications of NIR-LED photobiomodulation. Photomed Laser Surg 24:121–8PubMedCrossRefGoogle Scholar
  46. 46.
    Cerchietti LC, Navigante AH, Bonomi MR,. et al. 2002; Effect of topical morphine for mucositis-associated pain following concomitant chemoradiotherapy for head and neck carcinoma. Cancer 95:2230–6PubMedCrossRefGoogle Scholar
  47. 47.
    Barasch A, Elad S, Altman A, Damato K, Epstein J. 2006; Antimicrobials, mucosal coating agents, anesthetics, analgesics, and nutritional supplements for alimentary tract mucositis. Support Care Cancer 14:528–32PubMedCrossRefGoogle Scholar
  48. 48.
    Rubenstein EB, Peterson DE, Schubert M,. et al. 2004; Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer 100:2026–46PubMedCrossRefGoogle Scholar
  49. 49.
    Scully C, Sonis S, Diz PD. 2006; Oral mucositis. Oral Dis 12:229–41PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science + Business Media, LLC 2009

Authors and Affiliations

  • Nathaniel Treister
    • 1
  • Stephen Sonis*
    • 1
  1. 1.Department of Surg/Oral MedicineBrigham and Women’s Hospital, Harvard School of Dental MedicineBostonUSA

Personalised recommendations