Supportive Care in Cancer

, Volume 14, Issue 6, pp 533–540 | Cite as

The role of alternative and natural agents, cryotherapy, and/or laser for management of alimentary mucositis

  • Cesar A. MiglioratiEmail author
  • Loree Oberle-Edwards
  • Mark Schubert
Review Article


Goals of work

To review the literature and update the current guidelines of alternative/natural agents, cryotherapy, and/or laser therapy in the management of alimentary mucositis (AM).

Materials and methods

The original guidelines developed by the Multinational Association for Supportive Care in Cancer (MASCC)/International Society for Oral Oncology (ISOO) mucositis study group were the basis for this study. A medical librarian conducted an initial Medline search to identify research articles published between 2002 and 2005 in English language. A search term combination that included stomatitis, mucositis, mucous membrane, neoplasm, lasers, complimentary therapies, amino acids, antioxidants, vitamins, minerals, plant extracts, and cryotherapy was conducted. This initial search identified articles with a strong scientific methodology that included both preclinical and clinical research. Using standardized scoring forms, authors reviewed and scored individual articles. A consensus result of the review was achieved in a meeting of reviewers in June of 2005.


The initial search identified a total of 167 new articles. Of these, 14 were selected and reviewed: alternative/natural therapy (one preclinical study); cryotherapy (four clinical studies); lasers (two clinical studies); and alternative/natural agents (seven clinical studies). A new guideline could be established for the use of cryotherapy in the management of AM in hematopoietic stem cell transplant (HSCT) patients receiving melphalan in the conditioning phase.


The rapid progress in the understanding of AM created a need for new prevention and management protocols. Frequent literature review is now necessary to identify agents and protocols being developed in this important area of supportive care in cancer.


Stomatitis Mucositis Cryotherapy Laser Natural agents 


  1. 1.
    Adjei AA (2003) Pemetrexed (Alimta): a novel multitargeted antifolate agent. Expert Rev Anticancer Ther 3:145–156CrossRefPubMedGoogle Scholar
  2. 2.
    Aisa Y, Mori T, Kudo M, Yashima T, Kondo S, Yokoyama A, Ikeda Y, Okamoto S (2005) Oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis in allogeneic hematopoietic stem cell transplant recipients. Support Care Cancer 13:266–269CrossRefPubMedGoogle Scholar
  3. 3.
    Anderson PM, Ramsay NK, Shu XO, Rydholm N, Rogosheske J, Nicklow R, Weisdorf DJ, Skubitz KM (1998) Effect of low-dose oral glutamine on painful stomatitis during bone marrow transplantation. Bone Marrow Transplant 22:339–344CrossRefPubMedGoogle Scholar
  4. 4.
    Anderson PM, Schroeder G, Skubitz KM (1998) Oral glutamine reduces the duration and severity of stomatitis after cytotoxic cancer chemotherapy. Cancer 83:1433–1439CrossRefPubMedGoogle Scholar
  5. 5.
    Barasch A, Peterson DE, Tanzer JM (1995) Helium–neon laser effects on conditioning-induced oral mucositis in bone marrow transplantation patients. Cancer 76:2550–2556PubMedCrossRefGoogle Scholar
  6. 6.
    Bensadoun RJ, Ciais G, Darcourt V, Schhubert MM, Viot M, Dejou J, Tardieu C, Benezery K, Nguyen TD, Landoyer Y, Dassonville O, Poissonnet G, Vallicioni J, Thyss A, Hamdi M, Chauvel P, Demand F (1999) Low-energy H/Ne laser in the prevention of radiation-induced mucositis. A multicenter phase III randomized study in patients with head and neck cancer. Support Care Cancer 7:244–252CrossRefPubMedGoogle Scholar
  7. 7.
    Branda RF, Naud SJ, Brooks EM, Chen Z, Muss H (2004) Effect of vitamin B12, folate, and dietary supplements on breast carcinoma chemotherapy-induced mucositis and neutropenia. Cancer 101:1058–1064CrossRefPubMedGoogle Scholar
  8. 8.
    Cascinu S, Fedeli A, Fedeli SL, Catalano G (1994) Oral cooling (cryotherapy, an effective treatment for the prevention of 5-fluorouracil-induced stomatitis. Eur J Cancer Part B Oral Oncol 9:449–452Google Scholar
  9. 9.
    Cowen D, Tardieu C, schubert MM (1997) Low energy helium–neon laser in the prevention of oral mucositis in patients undergoing bone marrow transplant: results of a double blind randomized trial. Int J Radiat Oncol Biol Phys 38:697–703CrossRefPubMedGoogle Scholar
  10. 10.
    Edelman MJ, Gandara DR, Perez EA (1998) Phase I trial of edatrexate plus carboplatin in advanced solid tumors: amelioration of dose-limiting mucositis by ice chip cryotherapy. Invest New Drugs 16:69–75CrossRefPubMedGoogle Scholar
  11. 11.
    Ferreira PR, Fleck JF, Diehl A, Barletta D, Braga-Filho A, Barletta A, Ilha L (2004) Protective effect of alpha-tocopherol in head and neck cancer radiation-induced mucositis: a double-blind randomized trial. Head Neck 26:313–321CrossRefPubMedGoogle Scholar
  12. 12.
    Hadorn D, Baker D, Hodges J, Hicks N (1996) Rating the quality of evidence for clinical practice guidelines. J Clin Epidemiol 49:749–754CrossRefPubMedGoogle Scholar
  13. 13.
    KneeboneA, Mameghan H, Bolin T (2001) The effect of oral sucralfate on the acute proctitis associated with prostate radiotherapy: a double-blind, randomized trial. Int J Radiat Oncol Biol Phys 51:628–635CrossRefPubMedGoogle Scholar
  14. 14.
    Kokkonen J, Mottonen M, Karttunen TJ, Lanning M (2002) Mucosal pathology of the upper gastrointestinal tract associated with intensive chemotherapy in children: vitamin A supplements do not prevent lesions. Pediatr Hematol Oncol 19:181–192CrossRefPubMedGoogle Scholar
  15. 15.
    Kwong KKF (2004) Prevention and treatment of oropharyngeal mucositis following cancer therapy. Cancer Nurs 27:183–205CrossRefPubMedGoogle Scholar
  16. 16.
    Mahood DJ, Dose AM, Loprinzi CL, Veeder MH, Athman LM, Therneau TM, Sorensen JM, Gainey DK, Maillard JA, Gusa NL (1991) Inhibition of fluorouracil-induced stomatitis by oral cryotherapy. JCO 9:449452Google Scholar
  17. 17.
    Martenson JA, Bollinger JW, Sloan JA (2000) Sucralfate in the prevention of treatment-induced diarrhea in patients receiving pelvic radiation therapy: a North Central Cancer Treatment Group Phase III double-blind placebo-controlled trial. J Clin Oncol 18:1239–1245PubMedGoogle Scholar
  18. 18.
    Nakamura K, Yamada K, Baba M, Oshinaka H, Fukomoto T, Aikou T (1996) Prophylactic action of allopurinol against chemotherapy-induced stomatitis. Anticancer Drugs 7:235–239PubMedCrossRefGoogle Scholar
  19. 19.
    Nes AG, Posso MBS (2005) Patients with moderate chemotherapy-induced mucositis: pain therapy using low intensity lasers. Int Nurs Rev 52:68–72CrossRefPubMedGoogle Scholar
  20. 20.
    Piccirillo N, De Matteis S, Laurenti L, Chiusolo P, Sora F, Pittiruti M, Rutella S, Cicconi S, Fiorini A, D’Onofrio G, Leone G, Sica A (2003) Glutamine-enriched parenteral nutrition after autologous peripheral blood stem cell transplantation: effects on immune reconstitution and mucositis. Haematologica 88:192–200PubMedGoogle Scholar
  21. 21.
    Prince HM, Regester G, Gates P, Jablosnkis 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 11:512–520CrossRefPubMedGoogle Scholar
  22. 22.
    Rezvani M, Ross GA (2004) Modification of radiation-induced acute oral mucositis in the rat. Int J Radiat Biol 80:177–182CrossRefPubMedGoogle Scholar
  23. 23.
    Rocke LK, Loprinzi CL, Lee JKA (1993) Randomized clinical trial of two different durations of oral cryotherapy for prevention of 5-fluorouracil-induced stomatitis. Cancer 72:2234–2238PubMedCrossRefGoogle Scholar
  24. 24.
    Rubesntein EB, Peterson DE, Schubert M, Keefe D, McGuire D, Epstein J, Elting LS, FoxPC, Cooksley C, Sonis ST (2004) Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer 100(9 suppl):2026–2046CrossRefPubMedGoogle Scholar
  25. 25.
    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. Classic Papers Current Comments 4:881–886Google Scholar
  26. 26.
    Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, Bekele BN, Raver-Durlacher J, Donnely JP, Rubenstein EB (2004) Prospectives on cancer therapy-induced mucosal injury. Cancer 100(9 suppl):1995–2025CrossRefPubMedGoogle Scholar
  27. 27.
    Su CK, Mehta V, Ravikumar L, Shah R, Pinto H, Halpern J, Koong A, Goffinet D, Le Q-T (2004) Phase II double-blind randomized study comparing oral aloe vera versus placebo to prevent radiation-related mucositis in patients with head-and-neck neoplasms. Int J Radiat Oncol Biol Phys 60:171–177CrossRefPubMedGoogle Scholar
  28. 28.
    Tartarone A, Matera R, Romano G, Vigliotti ML, DiRenzo N (2005) Prevention of high-dose melphalan-induced mucositis by cryotherapy. Leuk Lymphoma 46:633–634PubMedCrossRefGoogle Scholar
  29. 29.
    Wadleigh RG, Redman RS, Graham ML, Krasnow SH, Anderson A, Cohen MH (1992) Vitamin E in the treatment of chemotherapy-induced mucositis. Am J Med 92:481–484CrossRefPubMedGoogle Scholar
  30. 30.
    Wong SF, Wilder-Smith P (2002) Pilot study of laser effects on oral mucositis in patients receiving chemotherapy. Cancer J 8:247–254PubMedCrossRefGoogle Scholar
  31. 31.
    Worthington HV, Clarkson JE (2002) Prevention of oral mucositis and oral candidiasis for patients with cancer treated with chemotherapy: cochrane systematic review. J Dent Educ 66:903–911PubMedGoogle Scholar
  32. 32.
    Yokomizo H, Yoshimatsu K, Hashimoto M, Ishibashi K, Umehara A, Yoshida K, Fujimoto T, Watanabe K, Ogawa K (2004) Prophylactic efficacy of allopurinol ice balls for leucovorin/5-fluorouracil therapy-induced stomatitis. Anticancer Res 24:1131–1134PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Cesar A. Migliorati
    • 1
    Email author
  • Loree Oberle-Edwards
    • 2
  • Mark Schubert
    • 3
  1. 1.Department of Diagnostic SciencesNova Southeastern University College of Dental MedicineFort LauderdaleUSA
  2. 2.Scripps Center for Dental CareLa JollaUSA
  3. 3.Oral Medicine ServiceFred Hutchinson Cancer Research CenterSeattleUSA

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