Drugs & Aging

, Volume 17, Issue 4, pp 257–267 | Cite as

Chemotherapy-Induced Oral Mucositis

Prevention and Management
  • Jennifer J. Knox
  • Anitasha L. V. Puodziunas
  • Ronald Feld
Disease Management


Oral mucositis is a frequent and potentially severe complication of chemotherapy which has a considerable impact on patient quality of life. While the management of other chemotherapy-related toxicities has improved, the incidence of mucositis is increasing. A critical review of the literature published between 1985 and 1999 reveals very few strategies or agents with proven efficacy, leaving few recommendations for the standard care in the prevention and treatment of mucositis at this time. Recommendations that can be made include: reducing patient risk factors, implementing proven preventative interventions such as utilising oral ice chips with fluorouracil chemotherapy, and optimising supportive care practices individualised to the patients’ needs and symptoms. Progress in understanding the pathophysiology of mucositis at the molecular level has led to the evaluation of a number of new investigational agents, specifically those directed to the epithelial mucosa, such as mitogens and epithelial growth factors. These appear to be very promising in preclinical studies. Randomised clinical trials with these agents may finally demonstrate an impact on the clinical practice of mucositis management in the coming years.


Betacarotene Misoprostol Oral Mucositis Tretinoin Keratinocyte Growth Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Rubenstein EB. Evaluating cost-effectiveness in outpatient management of medical complications in cancer patients. Curr Opin Oncol 1998; 10: 297–301PubMedCrossRefGoogle Scholar
  2. 2.
    Sonis ST, Sonis AL, Liekerman A. Oral complications in patients receiving treatment for malignancies other than the head and neck. J Am Dent Assoc 1979; 97: 468–72Google Scholar
  3. 3.
    Mahood DJ, Dose AM, Loprinzi CL, et al. Inhibition of fluoro-uracil-induced stomatitis by oral cryotherapy. J Clin Oncol 1991; 9: 449–52PubMedGoogle Scholar
  4. 4.
    Loprinzi CL, Dose AM. Studies on the prevention of 5-fluorouracil-induced oral mucositis. NCI Monogr 1990; 9: 93–4PubMedGoogle Scholar
  5. 5.
    Woo SB, Sonis ST, Monopoli MM, et al. A longitudinal study of oral ulcerative mucositis in bone marrow transplant recipients. Cancer 1993; 72: 1612–7PubMedCrossRefGoogle Scholar
  6. 6.
    Dodd MJ, Facione NC, Dibble SH, et al. Comparison of methods to determine the prevalence and nature of oral mucositis. Cancer Pract 1996; 4(6): 312–8PubMedGoogle Scholar
  7. 7.
    McCarthy GM, Awde JD, Gtardi H, et al. Risk factors associated with mucositis in cancer patients receiving 5-FU. Oral Oncol 1998; 34: 484–90PubMedCrossRefGoogle Scholar
  8. 8.
    Sonis ST. Mucositis as a biological process: a new hypothesis for the development of chemotherapy-induced stomatotoxicity. Oral Oncol 1998; 34: 39–43PubMedCrossRefGoogle Scholar
  9. 9.
    Sonis S, Tracey C, Shklar G, et al. An animal model for mucositis induced by cancer chemotherapy. Oral Surg Oral Med Oral Pathol 1990; 69: 437–43PubMedCrossRefGoogle Scholar
  10. 10.
    Porta C, Moroni M, Nastasi G. Allopurinol mouthwashes in the treatment of 5-fluorouracil-induced stomatitis. Am J Clin Oncol 1994; 17: 246–7PubMedCrossRefGoogle Scholar
  11. 11.
    Loprinzi CL, Cianflone SG, Dose AM, et al. A controlled evaluation of an allopurinol mouthwash as prophylaxis against 5-florouracil-induced stomatitis. Cancer 1990; 65: 1879–82PubMedCrossRefGoogle Scholar
  12. 12.
    Levi F, Zidani R, Missel JL. Randomized multicentre trial of chronotherapy with oxaliplatin, fluorouracil, and folinic acid in metastatic colorectal cancer. Lancet 1997; 350: 681–6PubMedCrossRefGoogle Scholar
  13. 13.
    Cascinu S, Fedeli A, Fedeli SL, et al. Oral cooling (cryotherapy), an effective treatment for the prevention of 5-fluorouracil-induced stomatitis. Eur J Cancer B Oral Oncol 1994; 30B: 234–6PubMedCrossRefGoogle Scholar
  14. 14.
    Sato A, Kumagai S, Sakaki K, et al. Inhibition of 5-fluorouracil-cisplatin-induced stomatitis by oral cryotherapy: use of an ice-bar containing fibrinolysin and deoxyribonuclease combine (Elase) [in Japanese]. Gan To Kagaku Ryoho 1997; 24: 1135–9PubMedGoogle Scholar
  15. 15.
    Rocke LK, Loprinzi CL, Lee JK, et al. A randomized clinical trial of two different durations of oral cryotherapy for prevention of 5-fluorouracil related stomatitis. Cancer 1993; 72: 2234–8PubMedCrossRefGoogle Scholar
  16. 16.
    Wolfrom C, Hartmann R, Fengler R, et al. Randomized comparison of 36-hour intermediate-dose versus 4-hour high-dose methotrexate infusions for remission induction in relapsed childhood acute lymphoblastic leukemia. J Clin Oncol 1993; 11:827–33PubMedGoogle Scholar
  17. 17.
    Ahmed T, Engelking C, Szalyga J, et al. Propantheline prevention of mucositis from etoposide. Bone Marrow Transplant 1993; 12: 131–2PubMedGoogle Scholar
  18. 18.
    Ackland SP, Schilsky RL. High-dose methotrexate: a critical re-appraisal. J Clin Oncol 1987; 5: 2017–31PubMedGoogle Scholar
  19. 19.
    Oliff A, Bleyer WA, Poplock DG. Methotrexate-induced oral mucositis and salivary methotrexate concentrations. Cancer Chemother Pharmacol 1979; 2: 225–5PubMedCrossRefGoogle Scholar
  20. 20.
    Mills ED. The modifying effect of beta-carotene on radiation and chemotherapy-induced oral mucositis. Br J Cancer 1988; 57: 416–7PubMedCrossRefGoogle Scholar
  21. 21.
    Labar B, Mrsic M, Pavletic Z, et al. Prostaglandin E2 for prophylaxis of oral mucositis following BMT. Bone Marrow Transplant 1993; 11: 379–82PubMedGoogle Scholar
  22. 22.
    Pettengell R, Gurney H, Radford JA, et al. Granulocyte colony-stimulating factor to prevent dose-limiting neutropenia in non-Hodgkin’s lymphoma: a randomized controlled trial. Blood 1992; 80: 1430–6PubMedGoogle Scholar
  23. 23.
    Katano M, Nakamura M, Matsuo T, et al. Effect of granulocyte colony-stimulating factor (G-CSF) on chemotherapy-induced oral mucositis. Surg Today 1995; 25: 202–6PubMedCrossRefGoogle Scholar
  24. 24.
    Karthaus M, Rosenthal C, Huebner G, et al. Effect of topical oral G-CSF on oral mucositis: a randomized placebo-controlled trial. Bone Marrow Transplant 1998; 22: 781–5PubMedCrossRefGoogle Scholar
  25. 25.
    Chi KH, Chen CH, Chan WK, et al. Effect of granulocyte-mac-rophage colony-stimulating factor on oral mucositis in head and neck cancer patients after cisplatin, fluorouracil, and leucovorin chemotherapy. J Clin Oncol 1995; 13: 2620–8PubMedGoogle Scholar
  26. 26.
    Nemunaitis J, Rosenfeld CS, Ash R, et al. Phase III randomized, double-blind placebo-controlled trial of rhGM-CSF following allogeneic bone marrow transplantation. Bone Marrow Transplant 1995; 15: 949–54PubMedGoogle Scholar
  27. 27.
    Jebb SA, Osborne RJ, Maughan TS, et al. 5-Flourouracil and folinic acid-induced mucositis: no effect of oral glutamine supplementation. Br J Cancer 1994; 70: 732–5PubMedCrossRefGoogle Scholar
  28. 28.
    Duenas-Gonzalez A, Sobrevilla-Calvo P, Frias-Medivil M, et al. Misoprostol prophylaxis for high-dose chemotherapy-induced mucositis: a randomized double-blind study. Bone Marrow Transplant 1996; 17: 809–12PubMedGoogle Scholar
  29. 29.
    Cohen G, Elad S, Or R, et al. The use of tretinoin as oral mucositis prophylaxis in bone marrow transplantation patients: a preliminary study. Oral Dis 1997; 3: 243–6PubMedCrossRefGoogle Scholar
  30. 30.
    Weite K, Zadler C, Reiter A, et al. Differential effects of GMCSF in children with severe congenital neutropenia. Blood 1990; 75: 1056–63Google Scholar
  31. 31.
    Wilkes JD. Prevention and treatment of oral mucositis following cancer chemotherapy. Semin Oncol 1998; 25(5): 538–51PubMedGoogle Scholar
  32. 32.
    Dedhar S, Gabomy L, Gallaway P, et al. Human GM-CSF is a growth factor active on a variety of cell types of non-hemato-poietic origin. Proc Natl Acad Sci U S A 1988; 85: 9253–7PubMedCrossRefGoogle Scholar
  33. 33.
    Zaghlonl MS, Dorce MJ, Kallman RF, et al. Interleukin-1 increases thymidine labelling index of normal tissue of mice but not the tumor. Int J Radiat Oncol Biol Phys 1994; 29: 805–11CrossRefGoogle Scholar
  34. 34.
    Sonis S, Muska A, O’Brien J, et al. Alteration in the frequency, severity and duration of chemotherapy-induced mucosits in hamsters by interleukin-11. Eur J Cancer B Oral Oncol 1996; 31B: 261–6Google Scholar
  35. 35.
    Sher CJ, Roberts JM. Inhibitors of mammalian Gl cyclin-dependent kinases. Genes Dev 1995; 9: 1149–63CrossRefGoogle Scholar
  36. 36.
    Spijkervet F, Sonis S. New frontiers in the management of chemotherapy-induced mucositis. Curr Opin Oncol 1998; 10Suppl. 1:523–7Google Scholar
  37. 37.
    Werner S. Keratinocyte growth factor: a unique player in epithelial repair processes. Cytokine Growth Factor Rev 1998; 9(2): 153–65PubMedCrossRefGoogle Scholar
  38. 38.
    Danilenko D. Pre-clinical and early clinical development of keratinocyte growth-factor. Toxicol Pathol 1999; 27(1): 64–71PubMedCrossRefGoogle Scholar
  39. 39.
    Ferretti GA, Ash RC, Brown AT, et al. Control of oral mucositis and candidiasis in marrow transplantation: a prospective, double-blind trial of chlorhexidine digluconate oral rinse. Bone Marrow Transplant 1988; 3: 483–93PubMedGoogle Scholar
  40. 40.
    Ferretti GA, Raybould TP, Brown AT, et al. Chlorhexidine prophylaxis for chemotherapy and radiotherapy-induced stomatitis: a randomized double-blind trial. Oral Surg Oral Med Oral Pathol 1990; 69: 331–8PubMedCrossRefGoogle Scholar
  41. 41.
    Rutkauskas JS, Davis JW. Effects of chlorhexidine during im-munosuppressive chemotherapy: a prelimininary report. Oral Surg Oral Med Oral Pathol 1993; 76: 441–8PubMedCrossRefGoogle Scholar
  42. 42.
    Bubley GJ, Chapman B, Chapman SK, et al. Effect of acyclovir on radiation and chemotherapy-induced mouth lesions. Anti-microb Agents Chemother 1989; 33: 862–5CrossRefGoogle Scholar
  43. 43.
    Bergmann OJ, Mogensen SC, Ellermann-Eriksen S, et al. Acyclovir prophylaxis and fever during remission-induction therapy of patients with acute mycloid leukemia: a randomized, double-blind, placebo-controlled trial. J Clin Oncol 1997; 15: 2269–74PubMedGoogle Scholar
  44. 44.
    Prada A, Chiesa F. Effects of benzydamine on the oral mucositis during antineoplastic radiotherapy and/or intra-arterial chemotherapy. Int J Tissue React 1987; 9: 115–9PubMedGoogle Scholar
  45. 45.
    Fidler P, Loprinzi CL, O’Fallon JR, et al. Prospective evaluation of a chamomile mouthwash for prevention of 5-FU-induced oral mucositis. Cancer 1996; 77: 522–5PubMedCrossRefGoogle Scholar
  46. 46.
    Weisdorf DJ, Bostrom B, Raether D, et al. Oropharyngeal mucositis complicating bone marrow transplantation: prognostic factors and the effect of chlorhexidine mouth rinse. Bone Marrow Transplant 1989; 4: 89–95PubMedGoogle Scholar
  47. 47.
    Wahlin BY. Effects of chlorhexidine mouthrinse on oral heal in patients with acute leukemia. Oral Surg Oral Med Oral Pathol 1989; 68: 279–87PubMedCrossRefGoogle Scholar
  48. 48.
    Dodd MJ, Larson PJ, Dibble SL, et al. Randomized clinical trial of chlorhexidine versus placebo for prevention of oral mucositis in patients receiving chemotherapy. Oncol Nurs Forum 1996; 23: 921–7PubMedGoogle Scholar
  49. 49.
    Borowski B, Benhamou E, Pico JL, et al. Prevention of oral mucositis in patients treated with high-dose chemotherapy and bone marrow transplantation: a randomized controlled trial comparing two protocols of dental care. Eur J Cancer B Oral Oncol 1994; 30B: 93–7PubMedCrossRefGoogle Scholar
  50. 50.
    Clift RA, Bianco JA, Appelbaum FR, et al. A randomized controlled trial of pentoxifylline for the prevention of regimenrelated toxicities in patients undergoing allogeneic marrow transplantation. Blood 1993; 82: 2025–30PubMedGoogle Scholar
  51. 51.
    Attal M, Huguet F, Rubie H, et al. Prevention of regimen-related toxicities after bone marrow transplantation by pentoxifylline: a prospective, randomized trial. Blood 1993; 82: 732–6PubMedGoogle Scholar
  52. 52.
    Verdi CJ, Garewal HS, Koenig LM, et al. A double-blind, randomized, placebo-controlled, crossover trial of pentoxifylline for the prevention of chemotherapy-induced oral mucositis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995; 80: 36–42PubMedCrossRefGoogle Scholar
  53. 53.
    Rahn R, Adamietz IA, Bõttcher FfD, et al. Povidone-iodine to prevent mucositis in patients during antineoplastic radio-chemotherapy. Dermatology 1997; 195Suppl. 2: 57–61PubMedCrossRefGoogle Scholar
  54. 54.
    Pfeiffer P, Madsen EL, Hansen O, et al. Effect of prophylactic sucralfate suspension on stomatitis induced by cancer chemotherapy: a randomized, double-blind cross-over study. Acta Oncol; 29: 171–3Google Scholar
  55. 55.
    Shenep JL, Kalwinsky DK, Hutson PR, et al. Efficacy of ora sucralfate suspention in prevention and treatment of chemotherapy-induced mucositis. J Pediatr 1988; 113: 758–63PubMedCrossRefGoogle Scholar
  56. 56.
    Loprinzi CL, Ghosh C, Camoriano J, et al. Phase III controlled evaluation of sucralfate to alleviate stomatitis in patients receiving fluorouracil-based chemotherapy. J Clin Oncol 1997; 15: 1235–8PubMedGoogle Scholar
  57. 57.
    Malik IA, Moid I, Haq S, et al. A double-blind, placebo-controlled, randomized trial to evaluate the role of tetrachlor-odecaoxide in the management of chemotherapy-induced oral mucosits. J Pain Symptom Manage 1997; 14(2): 82–7PubMedCrossRefGoogle Scholar
  58. 58.
    Wadleigh RG, Redman RS, Graham ML, et al. Vitamin E in the treatment of chemotherapy-induced mucositis. Am J Med 1992; 92: 481–4PubMedCrossRefGoogle Scholar
  59. 59.
    Lopez I, Goudou C, Ribrag V, et al. Treatment of mucositis with vitamine E prior to administration of myelosuppressive chemotherapy [in French]. Ann Med Interne Paris 1994; 52: 489–92Google Scholar
  60. 60.
    Feld R. The role of surveillance cultures in patients likely to develop chemotherapy-induced mucositis. Support Care Cancer 1997; 5: 371–5PubMedCrossRefGoogle Scholar
  61. 61.
    Abdelaal AS, Barker DS, Fergusson MM. Treatment for irradiation-induced mucositis [letter]. Lancet 1989; I: 97CrossRefGoogle Scholar
  62. 62.
    Beck S. The impact of a systematic oral care protocol on stomatitis after chemotherap. Cancer Nurs 1979; 2: 185–99PubMedCrossRefGoogle Scholar
  63. 63.
    Bondi E, Baroni C, Prete A, et al. Local antimicrobial therapy of oral mucositis in pediatric patients undergoing bone marrow transplantation. Oral Oncol 1997; 33: 322–6PubMedCrossRefGoogle Scholar
  64. 64.
    Loprinzi CL, Gastineau DA, Foote RL. Oral complications. In: Abeloff MD, Armitage JO, Allen SL, et al., editors. Clinical oncology. New York (NY): Churchill Livingstone, 2000: 965–97Google Scholar

Copyright information

© Adis International Limited 2000

Authors and Affiliations

  • Jennifer J. Knox
    • 1
  • Anitasha L. V. Puodziunas
    • 2
  • Ronald Feld
    • 1
    • 3
  1. 1.Department of Medical OncologyPrincess Margaret Hospital/University Health NetworkTorontoCanada
  2. 2.Department of PharmacyPrincess Margaret Hospital/University Health NetworkTorontoCanada
  3. 3.Department of MedicineUniversity of TorontoTorontoCanada

Personalised recommendations