Mucositis is an inflammatory reaction of the mucosa of the alimentary tract (AT) caused by chemotherapy, radiotherapy, and targeted therapy for cancer. It presents a significant burden not only to patient quality of life but also may result in diminished tumor control (through dose reductions) and increased treatment costs (due to extended hospital stays and supportive care). Mucositis symptoms may vary not only due to the treatment modality but also according to genetic predispositions of the patient toward developing toxicity (toxicogenomics). Management of mucositis is at present supportive only, with treatments that reduce incidence, severity, and duration of clinical symptoms, but do not prevent or cure mucositis altogether. A great deal of current research into the mechanisms involved in development and progression of mucositis is also being carried out; it is hoped that a clear understanding of mucositis pathophysiology, along with comprehensive toxicogenomics, will enable more preventative treatments to be developed.
This is a preview of subscription content, access via your institution.
Tax calculation will be finalised at checkout
Purchases are for personal use onlyLearn about institutional subscriptions
complementary and alternative medicine
hydrogen breath test
hematopoietic stem cell transplantation
low-level laser therapy
Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology
mechanistic target of rapamycin
National Cancer Institute Common Terminology Criteria for Adverse Events
nuclear factor kappa B
quality of life
randomized controlled trial
short bowel syndrome
13C-sucrose breath test
targeted anticancer therapy
total body irradiation
tyrosine kinase inhibitor
tumour necrosis factor
World Health Organization
Abimosleh SM, Tran CD, Howarth GS. Emu oil: a novel therapeutic for disorders of the gastrointestinal tract? J Gastroenterol Hepatol. 2012;27:857–61.
Abraham C, Cho JH. Inducing intestinal growth. N Engl J Med. 2005;353:2297–9.
Al-Dasooqi N, et al. Matrix metalloproteinases and their inhibitors are altered in a time-course model of irinotecan-induced mucositis. J Gastroenterol Hepatol. 2010;25(3):A2.
Al-Dasooqi N, et al. Emerging evidence on the pathobiology of mucositis. Support Care Cancer. 2013;21:3233–41.
Al-Dasooqi N, Wardill HR, Gibson RJ. Gastrointestinal mucositis: the role of MMP-tight junction interactions in tissue injury. Pathol Oncol Res. 2014;20:485–91.
Allen S, Kilian C, Phelps J, Whelan HT. The use of hyperbaric oxygen for treating delayed radiation injuries in gynecologic malignancies: a review of literature and report of radiation injury incidence. Support Care Cancer. 2012;20:2467–72.
Al-Mamgani A, et al. The impact of treatment modality and radiation technique on outcomes and toxicity of patients with locally advanced oropharyngeal cancer. Laryngoscope. 2013;123:386–93.
Al-Waili N, Salom K, Al-Ghamdi AA. Honey for wound healing, ulcers, and burns; data supporting its use in clinical practice. ScientificWorldJournal. 2011;11:766–87.
Aprile G, Ramoni M, Keefe D, Sonis S. Application of distance matrices to define associations between acute toxicities in colorectal cancer patients receiving chemotherapy. Cancer. 2008;112:284–92.
Aprile G, Ramoni M, Keefe D, Sonis S. Links between regimen-related toxicities in patients being treated for colorectal cancer. Curr Opin Support Palliat Care. 2009;3:50–4.
Arbabi-kalati F, Arbabi-kalati F, Deghatipour M, Ansari Moghadam A. Evaluation of the efficacy of zinc sulfate in the prevention of chemotherapy-induced mucositis: a double-blind randomized clinical trial. Arch Iran Med. 2012;15:413–7.
Bateman E, Keefe D. Patient-reported outcomes in supportive care. Semin Oncol. 2011;38:358–61.
Bateman EH, Bowen JM, Wignall A, Keefe DMK. Development of a fractionated radiotherapy model to investigate acute and chronic radiation-induced gastrointestinal injury in a Dark Agouti rat model. Supportive Care Cancer. 2012;20:1–283.
Bhanja P, et al. Protective role of R-spondin1, an intestinal stem cell growth factor, against radiation-induced gastrointestinal syndrome in mice. PLoS One. 2009;4:e8014.
Blijlevens N, et al. In a high-dose melphalan setting, palifermin compared with placebo had no effect on oral mucositis or related patient’s burden. Bone Marrow Transplant. 2013;48:966–71.
Boushey RP, Yusta B, Drucker DJ. Glucagon-like peptide (GLP)-2 reduces chemotherapy-associated mortality and enhances cell survival in cells expressing a transfected GLP-2 receptor. Cancer Res. 2001;61:687–93.
Bowen JM. Development of the rat model of lapatinib-induced diarrhoea. Scientifica (Cairo). 2014;2014:194185.
Bowen J, Gibson R, Cummins A, Tyskin A, Keefe D. Irinotecan changes gene expression in the small intestine of the rat with breast cancer. Support Care Cancer. 2006;14:629.
Bowen JM, et al. VSL#3 probiotic treatment reduces chemotherapy-induced diarrhea and weight loss. Cancer Biol Ther. 2007;6:1449–54.
Bowen JM, et al. Determining the mechanisms of lapatinib-induced diarrhoea using a rat model. Cancer Chemother Pharmacol. 2014;74:617–27.
Carlotto A, Hogsett VL, Maiorini EM, Razulis JG, Sonis ST. The economic burden of toxicities associated with cancer treatment: review of the literature and analysis of nausea and vomiting, diarrhoea, oral mucositis and fatigue. PharmacoEconomics. 2013;31:753–66.
Cheah KY, Howarth GS, Bastian SE. Grape seed extract dose-responsively decreases disease severity in a rat model of mucositis; concomitantly enhancing chemotherapeutic effectiveness in colon cancer cells. PLoS One. 2014;9:e85184.
Cho HK, Jeong YM, Lee HS, Lee YJ, Hwang SH. Effects of honey on oral mucositis in patients with head and neck cancer: a meta-analysis. Laryngoscope. 2015;125:2085–92.
Elad S, et al. Basic oral care for hematology-oncology patients and hematopoietic stem cell transplantation recipients: a position paper from the joint task force of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and the European Society for Blood and Marrow Transplantation (EBMT). Support Care Cancer. 2015;23:223–36.
Flichy-Fernandez AJ, et al. The effect of orally administered probiotic Lactobacillus reuteri-containing tablets in peri-implant mucositis: a double-blind randomized controlled trial. J Periodontal Res. 2015;50:775–85.
Gibson RJ, Bowen JM. Biomarkers of regimen-related mucosal injury. Cancer Treat Rev. 2011;37:487–93.
Gibson RJ, Stringer AM. Chemotherapy-induced diarrhoea. Curr Opin Support Palliat Care. 2009;3:31–5.
Gibson RJ, et al. Effect of interleukin-11 on ameliorating intestinal damage after methotrexate treatment of breast cancer in rats. Dig Dis Sci. 2002;47:2751–7.
Gibson RJ, Bowen JM, Inglis MR, Cummins AG, Keefe DM. Irinotecan causes severe small intestinal damage, as well as colonic damage, in the rat with implanted breast cancer. J Gastroenterol Hepatol. 2003;18:1095–100.
Gibson R, Bowen J, Alvarez E, Keefe D. Detailed investigation and comparison of single dose irinotecan-induced diarrhoea in Dark Agouti rats with and without tumours. Support Care Cancer. 2005;13:401–83.
Gibson RJ, et al. Systematic review of agents for the management of gastrointestinal mucositis in cancer patients. Support Care Cancer. 2013;21:313–26.
Gibson RJ, et al. Chemotherapy-induced gut toxicity and pain: involvement of TLRs. Support Care Cancer. 2016;24:2251–8.
Goldberg JD, et al. Palifermin is efficacious in recipients of TBI-based but not chemotherapy-based allogeneic hematopoietic stem cell transplants. Bone Marrow Transplant. 2013;48:99–104.
Hallstrom H, Lindgren S, Widen C, Renvert S, Twetman S. Probiotic supplements and debridement of peri-implant mucositis: a randomized controlled trial. Acta Odontol Scand. 2016;74:60–6.
Hawley P, Hovan A, McGahan CE, Saunders D. A randomized placebo-controlled trial of manuka honey for radiation-induced oral mucositis. Support Care Cancer. 2014;22:751–61.
Herbers AH, Feuth T, Donnelly JP, Blijlevens NM. Citrulline-based assessment score: first choice for measuring and monitoring intestinal failure after high-dose chemotherapy. Ann Oncol. 2010;21:1706–11.
Hoffmann M, et al. Long term results of postoperative Intensity-Modulated Radiation Therapy (IMRT) in the treatment of Squamous Cell Carcinoma (SCC) located in the oropharynx or oral cavity. Radiat Oncol. 2015;10:251.
Howarth GS, Tooley KL, Davidson GP, Butler RN. A non-invasive method for detection of intestinal mucositis induced by different classes of chemotherapy drugs in the rat. Cancer Biol Ther. 2006;5:1189–95.
Keefe DMK. Gastrointestinal mucositis: a new biological model. Support Care Cancer. 2004;12:6–9.
Keefe DM. Mucositis management in patients with cancer. Support Cancer Ther. 2006;3:154–7.
Keefe DM, Bateman EH. Tumor control versus adverse events with targeted anticancer therapies. Nat Rev Clin Oncol. 2012;9:98–109.
Keefe DMK, Bateman EH. Potential successes and challenges of targeted cancer therapies. J Natl Cancer Inst Monogr. In press.
Kelly N, et al. The role of the glutathione antioxidant system in gut barrier failure in a rodent model of experimental necrotizing enterocolitis. Surgery. 2004;136:557–66.
Kim KA, et al. Mitogenic influence of human R-spondin1 on the intestinal epithelium. Science. 2005;309:1256–9.
Kissow H, et al. Exogenous glucagon-like peptide-2 (GLP-2) prevents chemotherapy-induced mucositis in rat small intestine. Cancer Chemother Pharmacol. 2012;70:39–48.
Kissow H, Hartmann B, Holst JJ, Poulsen SS. Glucagon-like peptide-1 as a treatment for chemotherapy-induced mucositis. Gut. 2013;62:1724–33.
Kuchay RA. A review of complementary therapies for chemotherapy induced gastrointestinal mucositis. Drug Discov Ther. 2017;10(6):292–99.
Lalla RV, et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2014;120:1453–61.
Lee J, et al. Maintenance of colonic homeostasis by distinctive apical TLR9 signalling in intestinal epithelial cells. Nat Cell Biol. 2006;8:1327–36.
Logan RM, et al. The role of pro-inflammatory cytokines in cancer treatment-induced alimentary tract mucositis: pathobiology, animal models and cytotoxic drugs. Cancer Treat Rev. 2007a;33:448–60.
Logan RM, Gibson RJ, Sonis ST, Keefe DM. Nuclear factor-kappaB (NF-kappaB) and cyclooxygenase-2 (COX-2) expression in the oral mucosa following cancer chemotherapy. Oral Oncol. 2007b;43:395–401.
Logan RM, et al. Serum levels of NFkappaB and pro-inflammatory cytokines following administration of mucotoxic drugs. Cancer Biol Ther. 2008;7:1139–45.
Lotfi-Jam K, et al. Nonpharmacologic strategies for managing common chemotherapy adverse effects: a systematic review. J Clin Oncol. 2008;26:5618–29.
Lutgens L, Lambin P. Biomarkers for radiation-induced small bowel epithelial damage: an emerging role for plasma Citrulline. World J Gastroenterol. 2007;13:3033–42.
Lutgens LC, et al. Citrulline: a physiologic marker enabling quantitation and monitoring of epithelial radiation-induced small bowel damage. Int J Radiat Oncol Biol Phys. 2003;57:1067–74.
Lutgens LC, et al. Plasma citrulline concentration: a surrogate end point for radiation-induced mucosal atrophy of the small bowel. A feasibility study in 23 patients. Int J Radiat Oncol Biol Phys. 2004;60:275–85.
Lutgens LC, et al. Monitoring myeloablative therapy-induced small bowel toxicity by serum citrulline concentration: a comparison with sugar permeability tests. Cancer. 2005;103:191–9.
Mahood DJ, et al. Inhibition of fluorouracil-induced stomatitis by oral cryotherapy. J Clin Oncol. 1991;9:449–52.
Mashtoub S, et al. Emu oil combined with Lyprinol reduces small intestinal damage in a rat model of chemotherapy-induced mucositis. Nutr Cancer. 2016;68:1171–80.
McGuire DB, Correa ME, Johnson J, Wienandts P. The role of basic oral care and good clinical practice principles in the management of oral mucositis. Support Care Cancer. 2006;14:541–7.
McGuire DB, et al. Systematic review of basic oral care for the management of oral mucositis in cancer patients. Support Care Cancer. 2013;21:3165–77.
Mehdipour M, Zenoz AT, Kermani IA, Hosseinpour A. A comparison between zinc sulfate and chlorhexidine gluconate mouthwashes in the prevention of chemotherapy-induced oral mucositis. Daru. 2011;19:71.
Metri K, Bhargav H, Chowdhury P, Koka PS. Ayurveda for chemo-radiotherapy induced side effects in cancer patients. J Stem Cells. 2013;8:115–29.
Migliorati C, et al. Systematic review of laser and other light therapy for the management of oral mucositis in cancer patients. Support Care Cancer. 2013;21:333–41.
Pan CX, Morrison RS, Ness J, Fugh-Berman A, Leipzig RM. Complementary and alternative medicine in the management of pain, dyspnea, and nausea and vomiting near the end of life. A systematic review. J Pain Symptom Manag. 2000;20:374–87.
Pelton NS, Tivey DR, Howarth GS, Davidson GP, Butler RN. A novel breath test for the non-invasive assessment of small intestinal mucosal injury following methotrexate administration in the rat. Scand J Gastroenterol. 2004;39:1015–6.
Peterson DE, et al. Systematic review of oral cryotherapy for management of oral mucositis caused by cancer therapy. Support Care Cancer. 2013;21:327–32.
Peterson DE, et al. Oral mucosal injury caused by mammalian target of rapamycin inhibitors: emerging perspectives on pathobiology and impact on clinical practice. Cancer Med. 2016;5:1897–907.
Prisciandaro LD, Geier MS, Butler RN, Cummins AG, Howarth GS. Evidence supporting the use of probiotics for the prevention and treatment of chemotherapy-induced intestinal mucositis. Crit Rev Food Sci Nutr. 2011;51:239–47.
Raber-Durlacher JE, et al. Systematic review of cytokines and growth factors for the management of oral mucositis in cancer patients. Support Care Cancer. 2013;21:343–55.
Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell. 2004;118:229–41.
Rangwala F, Zafar SY, Abernethy AP. Gastrointestinal symptoms in cancer patients with advanced disease: new methodologies, insights, and a proposed approach. Curr Opin Support Palliat Care. 2012;6:69–76.
Rasmussen AR, et al. The intestinotrophic peptide, GLP-2, counteracts the gastrointestinal atrophy in mice induced by the epidermal growth factor receptor inhibitor, erlotinib, and cisplatin. Dig Dis Sci. 2010;55:2785–96.
Rubenstein EB, et al. Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer. 2004;100:2026–46.
Samdariya S, Lewis S, Kauser H, Ahmed I, Kumar D. A randomized controlled trial evaluating the role of honey in reducing pain due to radiation induced mucositis in head and neck cancer patients. Indian J Palliat Care. 2015;21:268–73.
Schwartz LK, et al. Long-term teduglutide for the treatment of patients with intestinal failure associated with short bowel syndrome. Clin Transl Gastroenterol. 2016;7:e142.
Smith K. The photobiological basis of low level laser radiation therapy. Laser Ther. 1991;3:19–24.
Song JJ, Twumasi-Ankrah P, Salcido R. Systematic review and meta-analysis on the use of honey to protect from the effects of radiation-induced oral mucositis. Adv Skin Wound Care. 2012;25:23–8.
Sonis ST. A biological approach to mucositis. J Support Oncol. 2004;2:21–32; discussion 35–6.
Sonis ST. Oral mucositis. Anti-Cancer Drugs. 2011;22:607–12.
Spielberger R, et al. Palifermin for oral mucositis after intensive therapy for hematologic cancers. N Engl J Med. 2004;351:2590–8.
Stringer AM. Interaction between host cells and microbes in chemotherapy-induced mucositis. Forum Nutr. 2013;5:1488–99.
Stringer A, et al. Mucositis, microflora and mucins: the effect of fluorouracil. Support Care Cancer. 2008;15:651–797.
Stringer AM, et al. Irinotecan-induced mucositis manifesting as diarrhoea corresponds with an amended intestinal flora and mucin profile. Int J Exp Pathol. 2009a;90:489–99.
Stringer AM, Gibson RJ, Bowen JM, Keefe DM. Chemotherapy-induced modifications to gastrointestinal microflora: evidence and implications of change. Curr Drug Metab. 2009b;10:79–83.
Stubbe CE, Valero M. Complementary strategies for the management of radiation therapy side effects. J Adv Pract Oncol. 2013;4:219–31.
Tooley KL, Howarth GS, Butler RN. Mucositis and non-invasive markers of small intestinal function. Cancer Biol Ther. 2009;8:753–8.
Van Sebille YZ, Gibson RJ, Wardill HR, Bowen JM. ErbB small molecule tyrosine kinase inhibitor (TKI) induced diarrhoea: chloride secretion as a mechanistic hypothesis. Cancer Treat Rev. 2015;41:646–52.
van Vliet MJ, et al. Citrulline as a marker for chemotherapy induced mucosal barrier injury in pediatric patients. Pediatr Blood Cancer. 2009;53:1188–94.
Walsh D, Rybicki L. Symptom clustering in advanced cancer. Support Care Cancer. 2006;14:831–6.
Wardill HR, et al. Irinotecan disrupts tight junction proteins within the gut: implications for chemotherapy-induced gut toxicity. Cancer Biol Ther. 2014a;15:236–44.
Wardill HR, Gibson RJ, Logan RM, Bowen JM. TLR4/PKC-mediated tight junction modulation: a clinical marker of chemotherapy-induced gut toxicity? Int J Cancer. 2014b;135:2483–92.
Wardill HR, Gibson RJ, Logan RM, Bowen JM. Does TLR4/PKC signalling drive chemotherapy induced barrier dysfunction and mucositis? Support Care Cancer. 2014c;22:S96.
Wardill H, et al. TLR4 deletion attenuates irinotecan-induced gut toxicity and barrier dysfunction in the Balb/C mouse offering a new therapeutic target. Support Care Cancer. 2015a;23(Suppl 1):1–388.
Wardill HR, et al. Toll-like receptor 4 signaling: a common biological mechanism of regimen-related toxicities: an emerging hypothesis for neuropathy and gastrointestinal toxicity. Cancer Treat Rev. 2015b;41:122–8.
Wardill HR, et al. Irinotecan-induced gastrointestinal dysfunction and pain are mediated by common TLR4-dependent mechanisms. Mol Cancer Ther. 2016a;15:1376–86.
Wardill HR, et al. TLR4-dependent claudin-1 internalization and secretagogue-mediated chloride secretion regulate irinotecan-induced diarrhea. Mol Cancer Ther. 2016b.
Xu JL, et al. Effects of honey use on the management of radio/chemotherapy-induced mucositis: a meta-analysis of randomized controlled trials. Int J Oral Maxillofac Surg. 2016.
Yao Q, et al. Protective effect of curcumin on chemotherapy-induced intestinal dysfunction. Int J Clin Exp Pathol. 2013;6:2342–9.
Yarom N, et al. Systematic review of natural agents for the management of oral mucositis in cancer patients. Support Care Cancer. 2013;21:3209–21.
Yeoh AS, et al. A novel animal model to investigate fractionated radiotherapy-induced alimentary mucositis: the role of apoptosis, p53, nuclear factor-kappaB, COX-1, and COX-2. Mol Cancer Ther. 2007;6:2319–27.
Yokomizo H, et al. Prophylactic efficacy of allopurinol ice ball for leucovorin/5-fluorouracil therapy-induced stomatitis. Anticancer Res. 2004;24:1131–4.
Zhao J, et al. R-Spondin1 protects mice from chemotherapy or radiation-induced oral mucositis through the canonical Wnt/beta-catenin pathway. Proc Natl Acad Sci U S A. 2009;106:2331–6.
Zhou WJ, Geng ZH, Spence JR, Geng JG. Induction of intestinal stem cells by R-spondin 1 and Slit2 augments chemoradioprotection. Nature. 2013;501:107–11.
Editors and Affiliations
© 2019 Springer Nature Switzerland AG
About this entry
Cite this entry
Bateman, E., Logan, R., Gibson, R., Keefe, D. (2019). Mucositis. In: MacLeod, R., Van den Block, L. (eds) Textbook of Palliative Care. Springer, Cham. https://doi.org/10.1007/978-3-319-77740-5_17
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-77738-2
Online ISBN: 978-3-319-77740-5