Skip to main content

Advertisement

Log in

Systematic review of natural and miscellaneous agents for the management of oral mucositis in cancer patients and clinical practice guidelines—part 1: vitamins, minerals, and nutritional supplements

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

A Correction to this article was published on 24 March 2021

This article has been updated

Abstract

Purpose

To update the clinical practice guidelines for the use of natural and miscellaneous agents for the prevention and/or treatment of oral mucositis (OM).

Methods

A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer / International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, the following guidelines were determined: Recommendation, Suggestion, and No Guideline Possible.

Results

A total of 78 papers were identified within the scope of this section, out of which 29 were included in this part, and were analyzed with 27 previously reviewed studies. A new Suggestion was made for oral glutamine for the prevention of OM in head and neck (H&N) cancer patients receiving radiotherapy with concomitant chemotherapy. The previous Recommendation against the use of parenteral glutamine for the prevention of OM in hematopoietic stem cell transplantation (HSCT) patients was re-established. A previous Suggestion for zinc to prevent OM in H&N cancer patients treated with radiotherapy or chemo-radiotherapy was reversed to No Guideline Possible. No guideline was possible for other interventions.

Conclusions

Of the vitamins, minerals, and nutritional supplements studied for the management of OM, the evidence supports a Recommendation against parenteral glutamine in HSCT patients and a Suggestion in favor of oral glutamine in H&N cancer patients for the management of OM.

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

Access this article

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

Change history

References

  1. Elad S, Zadik Y, Yarom N (2017) Oral complications of nonsurgical cancer therapies. Atlas Oral Maxillofac Surg Clin North Am 25:133–147

    Article  PubMed  Google Scholar 

  2. Keefe DM, Schubert MM, Elting LS, Sonis ST, Epstein JB, Raber-Durlacher JE, Migliorati CA, McGuire DB, Hutchins RD, Peterson DE, Mucositis study section of the Multinational Association of Supportive Care in C, the International Society for Oral O (2007) Updated clinical practice guidelines for the prevention and treatment of mucositis. Cancer 109:820–831

    Article  CAS  PubMed  Google Scholar 

  3. Rubenstein EB, Peterson DE, Schubert M, Keefe D, McGuire D, Epstein J, Elting LS, Fox PC, Cooksley C, Sonis ST, Mucositis study section of the Multinational Association for Supportive Care in C, International Society for Oral O (2004) Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer 100:2026–2046

    Article  PubMed  Google Scholar 

  4. Lalla RV, Bowen J, Barasch A, Elting L, Epstein J, Keefe DM, McGuire DB, Migliorati C, Nicolatou-Galitis O, Peterson DE, Raber-Durlacher JE, Sonis ST, Elad S, Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in C, International Society of Oral O (2014) MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 120:1453–1461

    Article  PubMed  Google Scholar 

  5. Jensen SB, Jarvis V, Zadik Y, Barasch A, Ariyawardana A, Hovan A, Yarom N, Lalla RV, Bowen J, Elad S, Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral O (2013) Systematic review of miscellaneous agents for the management of oral mucositis in cancer patients. Support Care Cancer 21:3223–3232

    Article  PubMed  Google Scholar 

  6. Yarom N, Ariyawardana A, Hovan A, Barasch A, Jarvis V, Jensen SB, Zadik Y, Elad S, Bowen J, Lalla RV, Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral O (2013) Systematic review of natural agents for the management of oral mucositis in cancer patients. Support Care Cancer 21:3209–3221

    Article  PubMed  Google Scholar 

  7. Ranna V, Cheng K, Castillo D, Porcello L, Vaddi A, Lalla R, Bossi P, Elad S (2019) Development of the MASCC/ISOO Clinical Practice Guidelines for Mucositis: an overview of the methods. Support Care Cancer

  8. Somerfield M, Padberg J, Pfister D, Bennett C, Recht A, Smith T, Weeks J, Winn R, Durant J (2000) ASCO clinical practice guidelines: process, progress, pitfalls, and prospects. Class Pap Curr Comments 4:881–886

    Google Scholar 

  9. 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  CAS  PubMed  Google Scholar 

  10. Ertekin MV, Koc M, Karslioglu I, Sezen O (2004) Zinc sulfate in the prevention of radiation-induced oropharyngeal mucositis: a prospective, placebo-controlled, randomized study. Int J Radiat Oncol Biol Phys 58(1):167–174

    Article  CAS  PubMed  Google Scholar 

  11. Doi H, Fujiwara M, Suzuki H, Niwa Y, Nakayama M, Shikata T, Odawara S, Takada Y, Kimura T, Kamikonya N, Hirota S (2015) Polaprezinc reduces the severity of radiation-induced mucositis in head and neck cancer patients. Mol Clin Oncol 3:381–386

    Article  PubMed  Google Scholar 

  12. Suzuki A, Kobayashi R, Shakui T, Kubota Y, Fukita M, Kuze B, Aoki M, Sugiyama T, Mizuta K, Itoh Y (2016) Effect of polaprezinc on oral mucositis, irradiation period, and time to discharge in patients with head and neck cancer. Head Neck 38:1387–1392

    Article  PubMed  Google Scholar 

  13. Lin LC, Que J, Lin LK, Lin FC (2006) Zinc supplementation to improve mucositis and dermatitis in patients after radiotherapy for head-and-neck cancers: a double-blind, randomized study. Int J Radiat Oncol Biol Phys 65:745–750

    Article  CAS  PubMed  Google Scholar 

  14. Lin YS, Lin LC, Lin SW, Chang CP (2010) Discrepancy of the effects of zinc supplementation on the prevention of radiotherapy-induced mucositis between patients with nasopharyngeal carcinoma and those with oral cancers: subgroup analysis of a double-blind, randomized study. Nutr Cancer 62:682–691

    Article  CAS  PubMed  Google Scholar 

  15. Watanabe T, Ishihara M, Matsuura K, Mizuta K, Itoh Y (2010) Polaprezinc prevents oral mucositis associated with radiochemotherapy in patients with head and neck cancer. Int J Cancer 127:1984–1990

    Article  CAS  PubMed  Google Scholar 

  16. Sangthawan D, Phungrassami T, Sinkitjarurnchai W (2013) A randomized double-blind, placebo-controlled trial of zinc sulfate supplementation for alleviation of radiation-induced oral mucositis and pharyngitis in head and neck cancer patients. J Med Assoc 96:69–76

    Google Scholar 

  17. Gorgu SZ, Ilknur AF, Sercan O, Rahsan H, Nalan A (2013) The effect of zinc sulphate in the prevention of radiation induced oral mucositis in patents with head and neck cancer. Int J Radiat Res 11:111–116

    Google Scholar 

  18. Moslemi D, Babaee N, Damavandi M, Pourghasem M, Moghadamnia AA (2014) Oral zinc sulphate and prevention of radiation-induced oropharyngeal mucositis in patients with head and neck cancers: a double blind, randomized controlled clinical trial. Int J Radiat Res 12:235–241

    Google Scholar 

  19. Mansouri A, Hadjibabaie M, Iravani M, Shamshiri AR, Hayatshahi A, Javadi MR, Khoee SH, Alimoghaddam K, Ghavamzadeh A (2012) The effect of zinc sulfate in the prevention of high-dose chemotherapy-induced mucositis: a double-blind, randomized, placebo-controlled study. Hematol Oncol 30:22–26

    Article  CAS  PubMed  Google Scholar 

  20. Hayashi H, Kobayashi R, Suzuki A, Ishihara M, Nakamura N, Kitagawa J, Kanemura N, Kasahara S, Kitaichi K, Hara T, Tsurumi H, Moriwaki H, Itoh Y (2014) Polaprezinc prevents oral mucositis in patients treated with high-dose chemotherapy followed by hematopoietic stem cell transplantation. Anticancer Res 34:7271–7277

    CAS  PubMed  Google Scholar 

  21. Arbabi-kalati F, Arbabi-kalati F, Deghatipour M, Ansari Moghadam A (2012) Evaluation of the efficacy of zinc sulfate in the prevention of chemotherapy-induced mucositis: a double-blind randomized clinical trial. Arch Iran Med 15:413–417

    CAS  PubMed  Google Scholar 

  22. Mehdipour M, Taghavi Zenoz A, Asvadi Kermani I, Hosseinpour A (2011) A comparison between zinc sulfate and chlorhexidine gluconate mouthwashes in the prevention of chemotherapy-induced oral mucositis. Daru 19:71–73

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Bhatt N, Naithani R, Gupta SK (2017) Supersaturated calcium phosphate rinse in prevention and treatment of mucositis in patients undergoing hematopoietic stem. Cell Transplant Exp Clin Transplant 15:567–570

    PubMed  Google Scholar 

  24. Papas AS, Clark RE, Martuscelli G, O'Loughlin KT, Johansen E, Miller KB (2003) A prospective, randomized trial for the prevention of mucositis in patients undergoing hematopoietic stem cell transplantation. Bone Marrow Transplant 31:705–712

    Article  CAS  PubMed  Google Scholar 

  25. Wasko-Grabowska A, Rzepecki P, Oborska S, Barzal J, Mlot B, Gawronski K, Wasko M, Szczylik C (2012) A supersaturated calcium phosphate solution seems to effectively prevent and treat oral mucositis in haematopoietic stem cell transplanted cancer patients - single centre experience. J BUON 17:363–368

    CAS  PubMed  Google Scholar 

  26. Wasko-Grabowska A, Rzepecki P, Oborska S, Barzal J, Gawronski K, Mlot B, Szczylik C (2011) Efficiency of supersaturated calcium phosphate mouth rinse treatment in patients receiving high-dose melphalan or BEAM prior to autologous blood stem cell transplantation: a single-center experience. Transplant Proc 43:3111–3113

    Article  CAS  PubMed  Google Scholar 

  27. Markiewicz M, Dzierzak-Mietla M, Frankiewicz A, Zielinska P, Koclega A, Kruszelnicka M, Kyrcz-Krzemien S (2012) Treating oral mucositis with a supersaturated calcium phosphate rinse: comparison with control in patients undergoing allogeneic hematopoietic stem cell transplantation. Support Care Cancer 20:2223–2229

    Article  PubMed  PubMed Central  Google Scholar 

  28. Svanberg A, Ohrn K, Birgegard G (2015) Caphosol((R)) mouthwash gives no additional protection against oral mucositis compared to cryotherapy alone in stem cell transplantation. A pilot study. Eur J Oncol Nurs 19:50–53

    Article  PubMed  Google Scholar 

  29. Raphael MF, den Boer AM, Kollen WJ, Mekelenkamp H, Abbink FC, Kaspers GJ, Zomer-Kooijker K, Molmans BH, Tissing WJ (2014) Caphosol, a therapeutic option in case of cancer therapy-induced oral mucositis in children?: results from a prospective multicenter double blind randomized controlled trial. Support Care Cancer 22:3–6

    Article  CAS  PubMed  Google Scholar 

  30. Lambrecht M, Mercier C, Geussens Y, Nuyts S (2013) The effect of a supersaturated calcium phosphate mouth rinse on the development of oral mucositis in head and neck cancer patients treated with (chemo)radiation: a single-center, randomized, prospective study of a calcium phosphate mouth rinse + standard of care versus standard of care. Support Care Cancer 21:2663–2670

    Article  PubMed  Google Scholar 

  31. Stokman MA, Burlage FR, Spijkervet FK (2012) The effect of a calcium phosphate mouth rinse on (chemo) radiation induced oral mucositis in head and neck cancer patients: a prospective study. Int J Dent Hyg 10:175–180

    Article  CAS  PubMed  Google Scholar 

  32. Bhatt V, Vendrell N, Nau K, Crumb D, Roy V (2010) Implementation of a standardized protocol for prevention and management of oral mucositis in patients undergoing hematopoietic cell transplantation. J Oncol Pharm Pract 16:195–204

    Article  CAS  PubMed  Google Scholar 

  33. Cluntun AA, Lukey MJ, Cerione RA, Locasale JW (2017) Glutamine metabolism in cancer: understanding the heterogeneity. Trends Cancer 3:169–180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Yildirim ZK, Bidev D, Buyukavci M (2013) Parenteral glutamine supplementation has no effect on chemotherapy-induced toxicity in children with non-Hodgkin lymphoma. J Pediatr Hematol Oncol 35:371–376

    Article  CAS  PubMed  Google Scholar 

  35. van Zaanen HC, van der Lelie H, Timmer JG, Furst P, Sauerwein HP (1994) Parenteral glutamine dipeptide supplementation does not ameliorate chemotherapy-induced toxicity. Cancer 74(10):2879–2884 1994 Nov 15 74: 2879-2884

    Article  PubMed  Google Scholar 

  36. Kuskonmaz B, Yalcin S, Kucukbayrak O, Cetin N, Cetin M, Tezcan I, Uckan D (2008) The effect of glutamine supplementation on hematopoietic stem cell transplant outcome in children: a case-control study. Pediatr Transplant 12(1):47–51

    Article  CAS  PubMed  Google Scholar 

  37. Schloerb PR, Skikne BS (1999) Oral and parenteral glutamine in bone marrow transplantation: a randomized, double-blind study. JPEN J Parenter Enteral Nutr 23:117–122

    Article  CAS  PubMed  Google Scholar 

  38. Pytlik R, Benes P, Patorkova M, Chocenska E, Gregora E, Prochazka B, Kozak T (2002) Standardized parenteral alanyl-glutamine dipeptide supplementation is not beneficial in autologous transplant patients: a randomized, double-blind, placebo controlled study. Bone Marrow Transplant 30:953–961

    Article  CAS  PubMed  Google Scholar 

  39. 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 S (2003) Glutamine-enriched parenteral nutrition after autologous peripheral blood stem cell transplantation: effects on immune reconstitution and mucositis. Haematologica 88:192–200

    CAS  PubMed  Google Scholar 

  40. Blijlevens NM, Donnelly JP, Naber AH, Schattenberg AV, DePauw BE (2005) A randomised, double-blinded, placebo-controlled, pilot study of parenteral glutamine for allogeneic stem cell transplant patients. Support Care Cancer 13:790–796

    Article  CAS  PubMed  Google Scholar 

  41. Uderzo C, Rebora P, Marrocco E, Varotto S, Cichello F, Bonetti M, Maximova N, Zanon D, Fagioli F, Nesi F, Masetti R, Rovelli A, Rondelli R, Valsecchi MG, Cesaro S (2011) Glutamine-enriched nutrition does not reduce mucosal morbidity or complications after stem-cell transplantation for childhood malignancies: a prospective randomized study. Transplantation 91:1321–1325

    Article  CAS  PubMed  Google Scholar 

  42. 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(4):339–344

    Article  CAS  PubMed  Google Scholar 

  43. Cockerham MB, Weinberger BB, Lerchie SB (2000) Oral glutamine for the prevention of oral mucositis associated with high-dose paclitaxel and melphalan for autologous bone marrow transplantation. Ann Pharmacother 34(3):300–303

    Article  CAS  PubMed  Google Scholar 

  44. Iyama S, Sato T, Tatsumi H, Hashimoto A, Tatekoshi A, Kamihara Y, Horiguchi H, Ibata S, Ono K, Murase K, Takada K, Sato Y, Hayashi T, Miyanishi K, Akizuki E, Nobuoka T, Mizugichi T, Takimoto R, Kobune M, Hirata K, Kato J (2014) Efficacy of enteral supplementation enriched with glutamine, fiber, and oligosaccharide on mucosal injury following hematopoietic stem cell transplantation. Case Rep Oncol 7:692–699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Coghlin Dickson TM, Wong RM, Offrin RS, Shizuru JA, Johnston LJ, Hu WW, Blume KG, Stockerl-Goldstein KE (2000) Effect of oral glutamine supplementation during bone marrow transplantation. JPEN J Parenter Enteral Nutr 24(2):61–66

    Article  CAS  PubMed  Google Scholar 

  46. Aquino VM, Harvey AR, Garvin JH, Godder KT, Nieder ML, Adams RH, Jackson GB, Sandler ES (2005) A double-blind randomized placebo-controlled study of oral glutamine in the prevention of mucositis in children undergoing hematopoietic stem cell transplantation: a pediatric blood and marrow transplant consortium study. Bone Marrow Transplant 36(7):611–616

    Article  CAS  PubMed  Google Scholar 

  47. Chattopadhyay S, Saha A, Azam M, Mukherjee A, Sur PK (2014) Role of oral glutamine in alleviation and prevention of radiation-induced oral mucositis: a prospective randomized study. South Asian J Cancer 3:8–12

    Article  PubMed  PubMed Central  Google Scholar 

  48. Tsujimoto T, Yamamoto Y, Wasa M, Takenaka Y, Nakahara S, Takagi T, Tsugane M, Hayashi N, Maeda K, Inohara H, Uejima E, Ito T (2015) L-glutamine decreases the severity of mucositis induced by chemoradiotherapy in patients with locally advanced head and neck cancer: a double-blind, randomized, placebo-controlled trial. Oncol Rep 33:33–39

    Article  CAS  PubMed  Google Scholar 

  49. Huang EY, Leung SW, Wang CJ, Chen HC, Sun LM, Fang FM, Yeh SA, Hsu HC, Hsiung CY (2000) Oral glutamine to alleviate radiation-induced oral mucositis: a pilot randomized trial. Int J Radiat Oncol Biol Phys 46(3):535–539

    Article  CAS  PubMed  Google Scholar 

  50. Sornsuvit C, Komindr S, Chuncharunee S, Wanikiat P, Archararit N, Santanirand P (2008) Pilot study: effects of parenteral glutamine dipeptide supplementation on neutrophil functions and prevention of chemotherapy-induced side-effects in acute myeloid leukaemia patients. J Int Med Res 36(6):1383–1391

    Article  CAS  PubMed  Google Scholar 

  51. Ward E, Smith M, Henderson M, Reid U, Lewis I, Kinsey S, Allgar V, Bowers D, Picton SV (2009) The effect of high-dose enteral glutamine on the incidence and severity of mucositis in paediatric oncology patients. Eur J Clin Nutr 63(1):134–140

    Article  CAS  PubMed  Google Scholar 

  52. Peterson DE, Jones JB, Petit RG (2007) 2nd Randomized, placebo-controlled trial of Saforis for prevention and treatment of oral mucositis in breast cancer patients receiving anthracycline-based chemotherapy. Cancer 109(2):322–331

    Article  CAS  PubMed  Google Scholar 

  53. Skubitz KM, Anderson PM (1996) Oral glutamine to prevent chemotherapy induced stomatitis: a pilot study. J Lab Clin Med 127(2):223–228

    Article  CAS  PubMed  Google Scholar 

  54. Rubio IT, Cao Y, Hutchins LF, Westbrook KC, Klimberg VS (1998) Effect of glutamine on methotrexate efficacy and toxicity. Ann Surg 227(5):772–778; discussion 778-80

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Anderson PM, Schroeder G, Skubitz KM (1998) Oral glutamine reduces the duration and severity of stomatitis after cytotoxic cancer chemotherapy. Cancer 83:1433–1439

    Article  CAS  PubMed  Google Scholar 

  56. Jebb SA, Osborne RJ, Maughan TS, Mohideen N, Mack P, Mort D, Shelley MD, Elia M (1994) 5-fluorouracil and folinic acid-induced mucositis: no effect of oral glutamine supplementation. Br J Cancer 70:732–735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Choi K, Lee SS, Oh SJ, Lim SY, Jeon WK, Oh TY, Kim JW (2007) The effect of oral glutamine on 5-fluorouracil/leucovorin-induced mucositis/stomatitis assessed by intestinal permeability test. Clin Nutr 26:57–62

    Article  CAS  PubMed  Google Scholar 

  58. Morishita T, Tsushita N, Imai K, Sakai T, Miyao K, Sakemura R, Kato T, Niimi K, Ono Y, Sawa M (2016) The efficacy of an Oral elemental diet in patients undergoing hematopoietic stem cell transplantation. Intern Med 55:3561–3569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Tanaka Y, Takahashi T, Yamaguchi K, Osada S, Shimokawa T, Yoshida K (2016) Elemental diet plus glutamine for the prevention of mucositis in esophageal cancer patients receiving chemotherapy: a feasibility study. Support Care Cancer 24:933–941

    Article  PubMed  Google Scholar 

  60. Ogata Y, Ishibashi N, Yamaguchi K, Uchida S, Kamei H, Nakayama G, Hirakawa H, Tanigawa M, Akagi Y (2016) Preventive effects of amino-acid-rich elemental diet Elental(R) on chemotherapy-induced oral mucositis in patients with colorectal cancer: a prospective pilot study. Support Care Cancer 24:783–789

    Article  PubMed  Google Scholar 

  61. Harada K, Ferdous T, Horinaga D, Uchida K, Mano T, Mishima K, Park S, Hanazawa H, Takahashi S, Okita A, Fukunaga M, Maruta J, Kami N, Shibuya K, Ueyama Y (2016) Efficacy of elemental diet on prevention for chemoradiotherapy-induced oral mucositis in patients with oral squamous cell carcinoma. Support Care Cancer 24:953–959

    Article  PubMed  Google Scholar 

  62. Galli F, Azzi A, Birringer M, Cook-Mills JM, Eggersdorfer M, Frank J, Cruciani G, Lorkowski S, Ozer NK (2017) Vitamin E: emerging aspects and new directions. Free Radic Biol Med 102:16–36

    Article  CAS  PubMed  Google Scholar 

  63. Khurana H, Pandey RK, Saksena AK, Kumar A (2013) An evaluation of vitamin E and pycnogenol in children suffering from oral mucositis during cancer chemotherapy. Oral Dis 19:456–464

    Article  CAS  PubMed  Google Scholar 

  64. Wadleigh RG, Redman RS, Graham ML, Krasnow SH, Anderson A (1992) Cohen MH vitamin E in the treatment of chemotherapy-induced mucositis. Am J Med 92(5):481–484

    Article  CAS  PubMed  Google Scholar 

  65. Sung L, Tomlinson GA, Greenberg ML, Koren G, Judd P, Ota S, Feldman BM (2007) Serial controlled N-of-1 trials of topical vitamin E as prophylaxis for chemotherapy-induced oral mucositis in paediatric patients. Eur J Cancer 43(8):1269–1275

    Article  CAS  PubMed  Google Scholar 

  66. 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(4):313–321

    Article  PubMed  Google Scholar 

  67. El-Housseiny AA, Saleh SM, El-Masry AA, Allam AA (2007) The effectiveness of vitamin “E” in the treatment of oral mucositis in children receiving chemotherapy. J Clin Pediatr Dent 31:167–170

    Article  PubMed  Google Scholar 

  68. Ryan-Harshman M, Aldoori W (2005) The relevance of selenium to immunity, cancer, and infectious/inflammatory diseases. Can J Diet Pract Res 66:98–102

    Article  PubMed  Google Scholar 

  69. Jahangard-Rafsanjani Z, Gholami K, Hadjibabaie M, Shamshiri AR, Alimoghadam K, Sarayani A, Mojtahedzadeh M, Ostadali-Dehaghi M, Ghavamzadeh A (2013) The efficacy of selenium in prevention of oral mucositis in patients undergoing hematopoietic SCT: a randomized clinical trial. Bone Marrow Transplant 48:832–836

    Article  CAS  PubMed  Google Scholar 

  70. Sugita J, Matsushita T, Kashiwazaki H, Kosugi M, Takahashi S, Wakasa K, Shiratori S, Ibata M, Shono Y, Shigematsu A, Obara M, Fujimoto K, Endo T, Nishio M, Kondo T, Hashino S, Tanaka J, Asaka M, Imamura M (2012) Efficacy of folinic acid in preventing oral mucositis in allogeneic hematopoietic stem cell transplant patients receiving MTX as prophylaxis for GVHD. Bone Marrow Transplant 47:258–264

    Article  CAS  PubMed  Google Scholar 

  71. Hamidieh AA, Sherafatmand M, Mansouri A, Hadjibabaie M, Ashouri A, Jahangard-Rafsanjani Z, Gholami K, Javadi MR, Ghavamzadeh A, Radfar M (2016) Calcitriol for oral mucositis prevention in patients with Fanconi anemia undergoing hematopoietic SCT: a double-blind, randomized, placebo-controlled trial. Am J Ther 23:e1700–e1708

    Article  PubMed  Google Scholar 

  72. Widemann BC, Adamson PC (2006) Understanding and managing methotrexate nephrotoxicity. Oncologist 11:694–703

    Article  CAS  PubMed  Google Scholar 

  73. Holick MF (2004) Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr 80:1678S–1688S

    Article  CAS  PubMed  Google Scholar 

  74. Chitapanarux I, Pisprasert V, Tharavichitkul E, Jakrabhandu S, Klunklin P, Onchan W, Supawongwattana B, Traisathit P, Rattanachaiwong S, Sattasiri WM (2016) Randomized study of nutritional status and treatment toxicities of oral arginine, glutamine, and omega-3 fatty acids during concurrent chemoradiotherapy for head and neck cancer patients. Funct Foods Health Dis 6:121–132

    Article  CAS  Google Scholar 

  75. Pattanayak L, Panda N, Dash MK, Mohanty S, Samantaray S (2016) Management of chemoradiation-induced mucositis in head and neck cancers with oral glutamine. J Glob Oncol 2:200–206

    Article  PubMed  PubMed Central  Google Scholar 

  76. Lopez-Vaquero D, Gutierrez-Bayard L, Rodriguez-Ruiz JA, Saldana-Valderas M, Infante-Cossio P (2017) Double-blind randomized study of oral glutamine on the management of radio/chemotherapy-induced mucositis and dermatitis in head and neck cancer. Mol Clin Oncol 6:931–936

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Pachon Ibanez J, Pereira Cunill JL, Osorio Gomez GF, Irles Rocamora JA, Serrano Aguayo P, Quintana Angel B, Fuentes Pradera J, Chaves Conde M, Ortiz Gordillo MJ, Garcia Luna PP (2018) Prevention of oral mucositis secondary to antineoplastic treatments in head and neck cancer by supplementation with oral glutamine. Nutr Hosp 35:428–433

    PubMed  Google Scholar 

  78. Nihei S, Sato J, Komatsu H, Ishida K, Kimura T, Tomita T, Kudo K (2018) The efficacy of sodium azulene sulfonate L-glutamine for managing chemotherapy-induced oral mucositis in cancer patients: a prospective comparative study. J Pharm Health Care Sci 4:20

    Article  PubMed  PubMed Central  Google Scholar 

  79. Okada T, Nakajima Y, Nishikage T, Ryotokuji T, Miyawaki Y, Hoshino A, Tokairin Y, Kawada K, Nagai K, Kawano T (2017) A prospective study of nutritional supplementation for preventing oral mucositis in cancer patients receiving chemotherapy. Asia Pac J Clin Nutr 26:42–48

    CAS  PubMed  Google Scholar 

  80. Ishikawa T, Yasuda T, Doi T, Okayama T, Sakamoto N, Gen Y, Dohi O, Yoshida N, Kamada K, Uchiyama K, Handa O, Takagi T, Konishi H, Yagi N, Kokura S, Naito Y, Itoh Y (2016) The amino acid-rich elemental diet Elental(R) preserves lean body mass during chemo- or chemoradiotherapy for esophageal cancer. Oncol Rep 36:1093–1100

    Article  CAS  PubMed  Google Scholar 

  81. Rambod M, Pasyar N, Ramzi M (2018) The effect of zinc sulfate on prevention, incidence, and severity of mucositis in leukemia patients undergoing chemotherapy. Eur J Oncol Nurs 33:14–21

    Article  PubMed  Google Scholar 

  82. Hayashi H, Kobayashi R, Suzuki A, Yamada Y, Ishida M, Shakui T, Kitagawa J, Hayashi H, Sugiyama T, Takeuchi H, Tsurumi H, Itoh Y (2016) Preparation and clinical evaluation of a novel lozenge containing polaprezinc, a zinc-L-carnosine, for prevention of oral mucositis in patients with hematological cancer who received high-dose chemotherapy. Med Oncol 33:7

    Article  CAS  Google Scholar 

  83. Wong KH, Kuciejewska A, Sharabiani MTA, Ng-Cheng-Hin B, Hoy S, Hurley T, Rydon J, Grove L, Santos A, Ryugenji M, Bhide SA, Nutting CM, Harrington KJ, Newbold KL (2017) A randomised controlled trial of Caphosol mouthwash in management of radiation-induced mucositis in head and neck cancer. Radiother Oncol 122:207–211

    Article  CAS  PubMed  Google Scholar 

  84. Treister N, Nieder M, Baggott C, Olson E, Chen L, Dang H, Krailo M, August A, Sung L (2017) Caphosol for prevention of oral mucositis in pediatric myeloablative haematopoietic cell transplantation. Br J Cancer 116:21–27

    Article  CAS  PubMed  Google Scholar 

  85. Kiprian D, Jarzabski A, Kawecki A (2016) Evaluation of efficacy of Caphosol in prevention and alleviation of acute side effects in patients treated with radiotherapy for head and neck cancers. Contemp Oncol (Pozn) 20:389–393

    CAS  Google Scholar 

Download references

Acknowledgments

The authors are thankful for the medical librarians for their valuable contribution to this project:

Lorraine Porcello, MSLIS, MSIM – Bibby Dental Library, Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY, USA; Daniel A. Castillo, MLIS – Edward G. Miner Library, University of Rochester Medical Center, Rochester, NY, USA.

Author information

Authors and Affiliations

Authors

Consortia

Corresponding author

Correspondence to Noam Yarom.

Ethics declarations

Conflict of interest

Per the MASCC Guidelines Policy, employees of commercial entities were not eligible to serve on this MASCC Guidelines Panel.

The authors disclose no conflict of interest (NY, AH, AA, SBJ, MG, HIH, AK, AM, GO, MP, NMN, TR, ASL, NST, EZ, VR, AV, KF, AB, SE). PB has served an advisory role for AstraZeneca, Helsinn, and Kyowa Kyrin and received grants from Merck, Kyowa Kyrin, and Roche.

RVL has served as a consultant for Colgate Oral Pharmaceuticals, Galera Therapeutics, Ingalfarma SA, Monopar Therapeutics, Mundipharma, and Sucampo Pharma; has received research support to his institution from Galera Therapeutics, Novartis, Oragenics, and Sucampo Pharma; and has received stock in Logic Biosciences.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yarom, N., Hovan, A., Bossi, P. et al. Systematic review of natural and miscellaneous agents for the management of oral mucositis in cancer patients and clinical practice guidelines—part 1: vitamins, minerals, and nutritional supplements. Support Care Cancer 27, 3997–4010 (2019). https://doi.org/10.1007/s00520-019-04887-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-019-04887-x

Keywords

Navigation