Head and Neck Cancer, Supportive Cancer Care
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Mucositis—Supportive Care During Radiotherapy or Chemoradiotherapy of Head and Neck Cancer

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Published Online: May 6th 2015 Oncology & Hematology Review, 2015;11(1):50–2 DOI:
Authors: Eli Sapir, Avraham Eisbruch
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Painful ulcers and sores and related dysphagia, thick saliva, taste impairment, and weight loss significantly affect the quality of life of head and neck cancer patients undergoing radiation treatment with or without concomitant chemotherapy. The available data for mucositis prophylaxis and treatment could be heterogeneous for clinical interpretation. In this editorial, we will describe what is already known and to outline the most important aspects of mucositis care.


Chemoradiotherapy, head and neck cancer, mucositis, radiotherapy, supportive care


The majority of patients undergoing radiation therapy for head and neck (HN) cancer will develop oral mucositis, which is a clinical syndrome characterized by erythema, ulcerations, and odynophagia (see Table 1). It is almost universal and more severe among patients with oral cavity, oropharynx, and nasopharynx primaries.1–3 Although therapeutic ratio and outcomes are improved by concominant chemotherapy4,5 or altered fractionation,6 both are related to dose-limiting mucositis and increase the risk for consequential dysphagia. Finally, mucositis is associated with unplanned breaks in radiation therapy, hospital admissions for pain management or insertion of enteral feeding tube,3 and is associated with increased costs.7 Reducing mucositis could be achieved by different means. This editorial will describe the available data and future perspectives in mucositis management.

Mouth Hygiene and Preventive Dental Care
Basic oral care protocols including daily topical fluoride, flossing, and frequent mouth rinses can be helpful for preventing and alleviating of mucositis.8,9 The evidence to support this approach is not strong, yet maintaining oral hygiene is supported by the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology(MASCC/ISOO) Clinical Practice Guidelines.10 Although different mouthwash preparations are available (normal saline, sodium bicarbonate, calcium phosphate), none of them had been consistently recommended by the gathered evidence-based data, but the panel suggested that they might beconsidered for oral care. The only rinse that the MASCC/ISOO recommended against was chlorhexidine mouthwash.10

Pretreatment dental care reduces risk for osteoradionecrosis.11 In addition, designing dental protective stents to prevent electron back-scatter off metal caps/bridges into the neighboring soft tissue could be beneficial for mucositis risk reduction.12–14

Reducing Mucositis by Antiviral/Antibacterial/ Mucosal Coating Agents
Different preparations including acyclovir, nystatin, fluconazole, sucralfate, and aluminum salt of sulfated sucrose were evaluated by multiple (mostly conflicting) studies. None of the above can be recommended to reduce chemoraditherapy mucositis.15

Newer mucosal protectants are available for HN cancer patients. Keratinocyte growth factor (palifermin) stimulates differentiation of mucosal cells. Two randomized studies have shown reduction of likelihood and median duration of severe mucositis, but narcotic use, patient-reported pain, and chemoradiotherapy compliance were not different from placebo.16,17 Marketed mucoadhesive hydrogel has been reported to significantly reduce patient-reported oral soreness and mucositis World Health Organization (WHO) score on the last day of radiation therapy compared with placebo,18 but it was not evaluated versus other preparations.

Pain Management
Pain is the main debilitating symptom of mucositis. Topical anesthetics, narcotics, and antidepressants could control it. While the former could not be advocated based on the available data,15 both topical morphine19,20 and transdermal fentanyl15,21 had been shown as highly effective in producing pain relief. In addition, long-acting opioid patches reduce the need for immediate-release opiates and provide lengthier freedom from pain.

Tricyclic antidepressants reduce patient-reported symptoms without affecting the severity of mucositis. A randomized, double-blind, crossover study22 of oral solution containing doxepin had shown significantly reduced mucositis pain compared with placebo, it was associated with more burning, unpleasant taste, and greater drowsiness, but most patients elected to continue doxepin during radiotherapy (RT) after the double-blind part of the study was completed.

Different recipes for solutions (so-called magic mouthwash solutions) containing a mix of different antibiotics, antihistamines, local anesthetics, an antifungal (e.g. nystatin), a corticosteroid, and antacids are in use; unfortunately, there are no data to show any benefit in alleviation of mucositis.10

Pharmacologic Prevention and Treatmentof Mucositis
Amifostine is an organic thiophosphate that competes with oxygen binding to the free radicals, which is essential to their activity in damaging the DNA, exerting a protective effect. The pro-drug is activated by membrane alkaline phosphatase, the concentration of which is lower in the acidic environment of cancer, potentially resulting in preferential protection of normal tissues. Unfortunately, besides the side effects (hypotension, nausea if administered parenterally, and skin reaction; local pain and nausea if injected subcutaneously), three randomized studies23–25 failed to show a definitive benefit of amifostine over placebo.

Better Radiosensitizers?
Epidermal growth factor receptor (EGFR) is overexpressed in the majority of HN tumors, suggesting a potential benefit of EGFR signaling pathway inhibition. Indeed, in the randomized phase III study26 RT concurrent with cetuximab (a monoclonal antibody to EGFR) resulted in improved tumorcontrol rates compared with RT alone with no difference in mucositis rates between the arms. Still, others27 report that cetuximab can induce enhanced mucosal injury. This finding could be potentially explained by heterogeneity in EGFR expression found in mucosal cells in different patients.28

Reduced Treatment Intensity
Human papillomavirus (HPV)-positive oropharyngeal cancer has a better prognosis, especially in patients without or with minimal smoking history.29 Overall survival in this favorable cohort exceeds 80 %. This yielded the following hypothesis: can we keep high tumor control-rates in these patients while reducing treatment intensity and toxicity? The phase II Eastern Cooperative Oncology Group (ECOG) 1308 study30 was designed to answer this question. If complete remission (CR) was achieved in the primary tumor following induction chemotherapy, the dose to the primary tumor bed was reduced to 54 Gy (instead of the standard dose of 70 Gy), concurrent with cerituximab. Local-regional control rate in these patients was 95 %. The ongoing phase III Quarterback trial will provide us with definite answers on this topic.

Mucositis-related Toxicity
Alterations in taste are dose dependent, and radiation to the anterior tongue and oral cavity seems to have the biggest effect.31 Preliminary data suggest zinc sulfate may alleviate these symptoms. Unfortunately this hypothesis was refuted by findings of the negative phase III study.32

N-acetyl cystein is a mucolytic that breaks disulfide bonds in mucus.33 We prescribe it after the completion of RT to patients who still suffer thick secretions, although data to support this recommendation are lacking.

Finally, to address complications related to significant weight loss caused by malnutrition, prophylactic insertion of percutaneous endoscopic gastrostomy (PEG) feeding tubes in all patients prior to RT start was compared with reactive feeding tubes in two randomized trials.34,35 Both found that prophylactic PEG resulted in less weight loss, improved patientreported quality of life (QOL), and lower long-term dysphagia. However, the benefit of prophylactic PEGs may come at the expense of longer dependence on PEG and increased late esophageal strictures requiring dilatation (30 % versus 6 %).36,37

HN patients following RT are affected in different ways, many of them related to mucositis. Proper management of mucosal damage by prophylactic (maintaining of mouth hygiene and dental care) and active (pain management, dose reduction when possible, and nutritional care) steps can substantially improve treatment-related QOL.

Article Information:

Eli Sapir, MD, and Avraham Eisbruch, MD, have no conflicts of interest to declare. No funding was received in the publication of this article.


Avraham Eisbruch, MD, Department of Radiation Oncology, University of Michigan Hospital, Ann Arbor, MI 48109, US. E:

Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit.




  1. Trotti A, Bellm LA, Epstein JB, et al., Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review, Radiother Oncol, 2003;66:253–62.
  2. Vera-Llonch M, Oster G, Hagiwara M, Sonis S, Oral mucositis in patients undergoing radiation treatment for head and neck carcinoma, Cancer, 2006;106:329–36.
  3. Elting LS, Cooksley CD, Chambers MS, Garden AS, Risk, outcomes, and costs of radiation-induced oral mucositis among patients with head-and-neck malignancies, Int J Radiat Oncol Biol Phys, 2007;68:1110–20.
  4. Pignon JP, Bourhis J, Domenge C, et al., Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: Three meta-analyses of updated individual data. MACH-NC collaborative group. Meta-analysis of chemotherapy on head and neck cancer, Lancet, 2000;355:949–55.
  5. Lee IH, Eisbruch A, Mucositis versus tumor control: the therapeutic index of adding chemotherapy to irradiation of head and neck cancer, Int J Radiat Oncol Biol Phys, 2009;75:1060–3.
  6. Bourhis J, Overgaard J, Audry H, Ang KK, et al., Hyperfractionated or accelerated radiotherapy in head and neck cancer: a metaanalysis, Lancet, 2006;368:843–54.
  7. Elting LS, Cooksley CD, Chambers MS, Garden AS, Risk, outcomes, and costs of radiation-induced oral mucositis among patients with head-and-neck malignancies, Int J Radiat Oncol Biol Phys, 2007;68:1110–20.
  8. 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.
  9. McGuire DB, Fulton JS, Park J, et al., Systematic review of basic oral care for the management of oral mucositis in cancer patients, Support Care Cancer, 2013;21:3165–77.
  10. Lalla RV, Bowen J, Barasch A, et al., MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy, Cancer, 2014;120:1453–61.
  11. Ben-David MA, Diamante M, Radawski JD, et al., Lack of osteoradionecrosis of the mandible after intensity-modulated radiotherapy for head and neck cancer: likely contributions of both dental care and improved dose distributions, Int J Radiat Oncol Biol Phys, 2007;68:396–402.
  12. Thilmann C, Adamietz IA, Ramm U, et al., In vivo dose increase in the presence of dental alloys during 60Co-gamma-ray therapy of the oral cavity, Med Dosim, 1996;21:149–54.
  13. Chin DW, Treister N, Friedland B, et al., Effect of dental restorations and prostheses on radiotherapy dose distribution: a Monte Carlo study, J Appl Clin Med Phys, 2009;10:2853.
  14. Reitemeier B, Reitemeier G, Schmidt A, et al., Evaluation of a device for attenuation of electron release from dental restorations in a therapeutic radiation field, J Prosthet Dent, 2002;87:323–7.
  15. Saunders DP, Epstein JB, Elad S, et al., Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients, Support Care Cancer, 2013;21:3191–207.
  16. Le QT, Kim HE, Schneider CJ, et al., Palifermin reduces severe mucositis in definitive chemoradiotherapy of locally advanced head and neck cancer: a randomized, placebo-controlled study, J Clin Oncol, 2011;29:2808–14.
  17. Henke M, Alfonsi M, Foa P, et al., Palifermin decreases severe oral mucositis of patients undergoing postoperative radiochemotherapy for head and neck cancer: a randomized, placebo-controlled trial, J Clin Oncol, 2011;29:2815–20.
  18. Allison RR, Ambrad AA, Arshoun Y, et al., Multi-institutional, randomized, double-blind, placebo-controlled trial to assess the efficacy of a mucoadhesive hydrogel (MuGard) in mitigating oral mucositis symptoms in patients being treated with chemoradiation therapy for cancers of the head and neck, Cancer, 2014;120:1433–40.
  19. Cerchietti LC, Navigante AH, Bonomi MR, et al., Effect of topical morphine for mucositis-associated pain following concomitant chemoradiotherapy for head and neck carcinoma, Cancer, 2002;95:2230–6.
  20. Cerchietti LC, Navigante AH, Körte MW, et al., Potential utility of the peripheral analgesic properties of morphine in stomatitisrelated pain: a pilot study, Pain, 2003;105:265–73.
  21. Chang JT, Lin CY, Lin JC, et al., Transdermal fentanyl for pain caused by radiotherapy in head and neck cancer patients treated in an outpatient setting: a multicenter trial in Taiwan, Jpn J Clin Oncol, 2010;40:307–12.
  22. Leenstra JL, Miller RC, Qin R, et al., Doxepin rinse versus placebo in the treatment of acute oral mucositis pain in patients receiving head and neck radiotherapy with or without chemotherapy: a phase III, randomized, double-blind trial, J Clin Oncol, 2014;32:1571–7.
  23. Buentzel J, Micke O, Adamietz IA, et al., Intravenous amifostine during chemoradiotherapy for head-and-neck cancer: a randomized placebo-controlled phase III study, Int J Radiat Oncol Biol Phys, 2006;64:684–91.
  24. Vacha P, Fehlauer F, Mahlmann B, et al., Randomized phase III trial of postoperative radiochemotherapy +/- amifostine in head and neck cancer. Is there evidence for radioprotection?, Strahlenther Onkol, 2003;179:385–9.
  25. Haddad R, Sonis S, Posner M, et al., Randomized phase 2 study of concomitant chemoradiotherapy using weekly carboplatin/ paclitaxel with or without daily subcutaneous amifostine in patients with locally advanced head and neck cancer, Cancer, 2009;115:4514–23.
  26. Bonner JA, Harari PM, Giralt J, et al., Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck, N Engl J Med, 2006;354:567–78.
  27. Pryor DI, Porceddu SV, Burmeister BH, et al., Enhanced toxicity with concurrent cetuximab and radiotherapy in head and neck cancer, Radiother Oncol, 2009;90:172–6.
  28. Tsien CI, Nyati MK, Ahsan A, et al., Effect of erlotinib on epidermal growth factor receptor and downstream signaling in oral cavity squamous cell carcinoma, Head Neck, 2013;35:1323–30.
  29. Ang KK, Harris J, Wheeler R, et al., Human papillomavirus and survival of patients with oropharyngeal cancer, N Engl J Med, 2010;363:24–35.
  30. Marur S, Lee J, Cmelak A, et al., Reduced-dose IMRT in human papilloma virus (HPV)-associated resectable oropharyngeal squamous carcinomas (OPSCC) after clinical complete response (cCR) to induction chemotherapy (IC), J Clin Oncol, 2014;32:5s (suppl; abstr LBA6006).
  31. Vernia N, Feng FY, Braun T, et al., Dosimetric predictors of taste impairment in patients treated with chemoradiation for head and neck cancer, IJROBP, 2009;75(Suppl):S179.
  32. Halyard MY, Jatoi A, Sloan JA, et al., Does zinc sulfate prevent therapy-induced taste alterations in head and neck cancer patients? Results of phase III double-blind, placebo-controlled trial from the North Central Cancer Treatment Group (N01C4), Int J Radiat Oncol Biol Phys, 2007;67:1318–22.
  33. Sheffner AL, The reduction in vitro in viscosity of mucoprotein solutions by a new mucolytic agent, N-acetyl-Lcysteine, Ann N Y Acad Sci, 1963;106:298–310.
  34. Salas S, Baumstarck-Barrau K, Alfonsi M, et al., Impact of the prophylactic gastrostomy for unresectable squamous cell head and neck carcinomas treated with radio-chemotherapy on quality of life: Prospective randomized trial, Radiother Oncol, 2009;93:503–9.
  35. Silander E, Nyman J, Bove M, et al., Impact of prophylactic percutaneous endoscopic gastrostomy on malnutrition and quality of life in patients with head and neck cancer: a randomized study, Head Neck, 2012;34:1–9.
  36. Chen AM, Li BQ, Lau DH, et al., Evaluating the role of prophylactic gastrostomy tube placement prior to definitive chemoradiotherapy for head and neck cancer, Int J Radiat Oncol Biol Phys, 2010;78:1026–32.
  37. Koyfman SA, Adelstein DJ, Enteral feeding tubes in patients undergoing definitive chemoradiation therapy for head-andneck cancer: a critical review, Int J Radiat Oncol Biol Phys, 2012;84:581–9.

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