Supportive Care in Cancer

, Volume 14, Issue 6, pp 499–504 | Cite as

Alimentary tract mucositis in cancer patients: impact of terminology and assessment on research and clinical practice

  • Douglas E. Peterson
  • Dorothy M. Keefe
  • Ronald D. Hutchins
  • Mark M. Schubert
Review Article


Background and significance

The field of terminology and assessment of oral and gastrointestinal mucosal injury caused by high-dose cancer therapies in cancer patients has undergone important evolution in recent years. The advances are important for several clinical and research reasons. These reasons include improved patient management and design and conduct of clinical trials based on molecularly targeted therapies. For several decades leading up to the 1980s, terminology was characterized by varying use of “mucositis” and “stomatitis” to describe oral mucosal inflammatory changes and ulceration caused by cancer treatments. In addition, oral mucositis was viewed principally as an epithelial event and one that likely did not intersect with causative mechanisms associated with gastrointestinal mucositis. The term “stomatitis” was directed to oral toxicities and seemed to isolate these conditions from parallel events occurring throughout the alimentary tract and potentially other tissues as well. These perspectives and varying use of these terms resulted in several dilemmas, including (1) difficulty in accurately reporting incidence and severity of oral mucositis and, (2) an underappreciation of potential significance of alimentary tract mucosal toxicity relative to overall course of therapy, patient quality of life, and in some cases, survivorship. These and related components of the model relative to mucositis have undergone strategic shifts over the past 15 years. A 1989 National Institutes of Health Consensus Development Conference targeted oral mucositis research as one of the key areas for investigation relative to causation, clinical impact, and potential links with other complications in cancer patients. Research in this area over the past 15 years has evolved such that oral and gastrointestinal mucositis are now appropriately framed as a continuum of pathobiologic changes over time, with clinical impact that may well contribute to overall symptom clustering in selected patient cohorts.


This paper will review history, current status, and new research directions associated with terminology and assessment of mucosal injury in cancer patients in the context described above.


  1. 1.
    Consensus statement: oral complications of cancer therapies (1990) NCI Monogr 9:3–8Google Scholar
  2. 2.
    Sonis ST, Elting LS, Keefe D et al (2004) Perspectives on cancer therapy-induced mucosal injury. Cancer Suppl 100/9:1995–2025Google Scholar
  3. 3.
    Rubenstein EB, Peterson DE, Schubert M et al (2004) Clinical practice guidelines for the prevention and management of cancer therapy-induced oral and gastrointestinal mucositis. Cancer Suppl 100/9:2026–2046Google Scholar
  4. 4.
    Keefe DM, Brealey J, Goland GJ, Cummins AG (2000) Chemotherapy for cancer causes apoptosis that precedes hypoplasia in crypts of the small intestine in humans. Gut 47:632–637PubMedCrossRefGoogle Scholar
  5. 5.
    Bowen JM, Gibson RJ, Keefe DM, Cummins AG (2005) Cytotoxic chemotherapy upregulates pro-apoptotix Bax and Bak in the small intestine of rats and humans. Pathology 37:56–62PubMedCrossRefGoogle Scholar
  6. 6.
    Gibson RJ, Bowen JM, Keefe DM (2005) Palifermin reduces diarrhea and increases survival following irinotecan treatment in tumor-bearing DA rats. Int J Cancer 116:464–470PubMedCrossRefGoogle Scholar
  7. 7.
    Gibson RJ, Bowen JM, Cummins AG, Keefe DM (2005) Relationship between dose of methotrexate, apoptosis, p53/p21 expression and intestinal crypt proliferation in the rat. Clin Exp Med 4:188–195PubMedCrossRefGoogle Scholar
  8. 8.
    Yeoh AS, Bowen JM, Gibson RJ, Keefe DM (2005) Nuclear factor kappaB (NFkappaB) and cycloxygenase-2 (Cox-2) expression in the irradiated colorectum is associated with subsequent histopathological changes. Int J Radiat Oncol Biol Phys 63:1295–1303PubMedCrossRefGoogle Scholar
  9. 9.
    Sonis ST, Rubenstein ER, Peterson DE (2003) Patient care: integrated education session. Proc Am Soc Clin OncolGoogle Scholar
  10. 10.
    Elting LS, Sonis ST, Keefe DM (2004) Education session, Proc Am Soc Clin OncolGoogle Scholar
  11. 11.
    Cella D, Pulliam J, Fuchs H et al (2003) Evaluation of pain associated with oral mucositis during the acute period after administration of high-dose chemotherapy. Cancer 98:406–412PubMedCrossRefGoogle Scholar
  12. 12.
    Cleeland CS, Bennett GJ, Dantzer R et al (2003) Are the symptoms of cancer and cancer treatment due to a shared biologic mechanism? A cytokine-immunologic model of cancer symptoms. Cancer 97:2919–2925PubMedCrossRefGoogle Scholar
  13. 13.
    Dodd MJ, Miaskowski C, Lee KA (2004) Occurrence of symptom clusters. J Natl Cancer Inst Monographs 32:76–78PubMedCrossRefGoogle Scholar
  14. 14.
    Miaskowski C, Dodd M, Lee K (2004) Symptom clusters: the new frontier in symptom management research. J Natl Cancer Inst Monographs 32:17–21PubMedCrossRefGoogle Scholar
  15. 15.
    Illman J, Corringham R, Robinson D Jr et al (2005) Are inflammatory cytokines the common link between cancer-associated cachexia and depression? J Support Oncol 1:37–50Google Scholar
  16. 16.
    Kim HJ, McGuire DB, Tulman L (2005) Symptom clusters: concept analysis and clinical implications for cancer nursing. Cancer Nurs 28:270–282PubMedGoogle Scholar
  17. 17.
    Trotti A, Colevas AD, Setser A et al (2003) CTCAE v3.0: Development of a comprehensive grading system for the adverse effects of cancer treatment. In: Trotti A, Rubin P (eds.) The adverse effects of cancer treatment: metrics, management, and investigations. Sem Rad Oncol 13:176–181Google Scholar
  18. 18.
    National Cancer Institute Cancer Therapy Evaluation Program (2006)
  19. 19.
    Sonis ST, Peterson DE, McGuire DB, Williams DA (eds.) (2001) Mucosal injury in cancer patients: new strategies for research and treatment. JNCI 29:1–54Google Scholar
  20. 20.
    Keefe DM (2004) Gastrointestinal mucositis: a new biological model. Supp Care Cancer 12:6–9CrossRefGoogle Scholar
  21. 21.
    Eilers J, Epstein JB (2004) Assessment and measurement of oral mucositis. In: McGuire DB, Peterson DE (eds.). Mucositis Sem Oncol Nurs 20:22–29Google Scholar
  22. 22.
    Chapko MK, Syrjala KL, Schilter L, Cummings C, Sullivan KM (1989) Chemoradiotherapy toxicity during bone marrow transplantation: time course and variation in pain and nausea. Bone Marrow Transplant 4:181–186PubMedGoogle Scholar
  23. 23.
    McGuire DB, Altomonte V, Peterson DE, Wingard JR, Jones RJ, Grochow LB (1993) Patterns of mucositis and pain in patients receiving preparative chemotherapy and bone marrow transplantation. Oncol Nurs Forum 20:1493–502PubMedGoogle Scholar
  24. 24.
    Stiff PJ, Emmanouilides C, Bensinger WI et al (2006) Palifermin reduces patient-reported mouth and throat soreness and improves patient functioning in the hematopoietic stem-cell transplantation setting. J Clin Oncol 24:1–8CrossRefGoogle Scholar
  25. 25.
    Melichar B, Kohout P, Bratova M et al (2001) Intestinal permeability in patients with chemotherapy-induced stomatitis. J Cancer Res Clin Oncol 127:314–318PubMedCrossRefGoogle Scholar
  26. 26.
    Lutgens LC, Blijlevens NM, Deutz NE et al (2005) Monitoring myelablative therapy-induced small bowel toxicity by serum citrulline concentration: A comparison with sugar permeability tests. Cancer 103:191–199PubMedCrossRefGoogle Scholar
  27. 27.
    Inglis K, Saxon B, Webster J et al (2005) Non-invasive assessment of chemotherapy-induced intestinal mucositis in children. Proc 17th Annual Multnatl Assoc Supp Care Cancer 13:445Google Scholar
  28. 28.
    Schubert MM (2004) Oro-pharyngeal mucositis. In: Atkinson K, Champlin R, Ritz J et al (eds) Clinical bone marrow and blood stem cell transplantation. Cambridge Univ. Press, Cambridge, p 1276Google Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Douglas E. Peterson
    • 1
  • Dorothy M. Keefe
    • 2
  • Ronald D. Hutchins
    • 3
  • Mark M. Schubert
    • 4
    • 5
  1. 1.Department of Oral Health and Diagnostic Sciences, School of Dental Medicine, Neag Comprehensive Cancer CenterUniversity of Connecticut Health CenterFarmingtonUSA
  2. 2.Department of Medical Oncology, Royal Adelaide Hospital Cancer CentreRoyal Adelaide HospitalAdelaideAustralia
  3. 3.Research Medical LibraryUniversity of Texas M.D. Anderson Cancer CenterHoustonUSA
  4. 4.Oral Medicine, School of DentistryUniversity of WashingtonSeattleUSA
  5. 5.Oral MedicineSeattle Cancer Care Alliance/Fred Hutchinson Cancer Research CenterSeattleUSA

Personalised recommendations