Management of Mucositis During Chemotherapy: From Pathophysiology to Pragmatic Therapeutics

Current Oncology Reports

Volumn 17, Issue 11, 2015, Pages

  Van Sebille, Ysabella Z A ^a   Stansborough, Romany ^a   Wardill, Hannah R ^a   Bateman, Emma ^a   Gibson, Rachel J ^a   Keefe, Dorothy M ^a  

^a UNIVERSITY OF ADELAIDE   (Australia)

Author keywords

Analgesics; Antimicrobials; Antioxidants; Benzydamine hydrochloride (HCl); Cancer side effects; Chemotherapy induced gut toxicity; Coating agents; Mucositis; Mucositis treatment; Palifermin; Probiotics; R spondin1; Toxicity; Zinc sulphate

Indexed keywords

ACETYLCYSTEINE; AMPHOTERICIN B; ANTINEOPLASTIC AGENT; BENZYDAMINE; CHLORHEXIDINE GLUCONATE; CISPLATIN; COLON DOPHILUS; DIPHENOXYLATE; DOXEPIN; DOXORUBICIN; FENTANYL; FLUCONAZOLE; FLUOROURACIL; GLUTAMINE; GLYCOPROTEIN; IFOSFAMIDE; IRINOTECAN; LOPERAMIDE; MELPHALAN; MICONAZOLE; MOUTHWASH; NYSTATIN; PALIFERMIN; PLACEBO; PROBIOTIC AGENT; R SPONDIN1; SUCRALFATE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VSL3; ZINC SULFATE; ANTIINFLAMMATORY AGENT; DRUG COMBINATION; GELCLAIR; HYALURONIC ACID; KERATINOCYTE GROWTH FACTOR; NONSTEROID ANTIINFLAMMATORY AGENT; POVIDONE; RSPO1 PROTEIN, HUMAN; THROMBOSPONDIN;

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; BREAST CANCER; CANCER RADIOTHERAPY; CHEMOPROPHYLAXIS; CHEMORADIOTHERAPY; COLORECTAL CANCER; DIARRHEA; DRUG EFFECT; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; HEAD AND NECK CANCER; HEMATOLOGIC MALIGNANCY; HUMAN; LACTOBACILLUS; LACTOBACILLUS RHAMNOSUS; LOW LEVEL LASER THERAPY; MOUTH MUCOSA; MOUTH PAIN; MUCOSA INFLAMMATION; NONHUMAN; ORAL MUCOSITIS; ORAL REHYDRATION THERAPY; PATHOPHYSIOLOGY; PRACTICE GUIDELINE; REVIEW; SARCOMA; SIDE EFFECT; SINGLE DRUG DOSE; TASTE DISORDER; XEROSTOMIA; CHEMICALLY INDUCED; DRUG COMBINATION; DRUG EFFECTS; GASTROINTESTINAL TRACT; INTESTINE MUCOSA; MUCOSITIS; PATHOLOGY;

ANTI-INFLAMMATORY AGENTS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ANTINEOPLASTIC AGENTS; DRUG COMBINATIONS; FIBROBLAST GROWTH FACTOR 7; GASTROINTESTINAL TRACT; HUMANS; HYALURONIC ACID; INTESTINAL MUCOSA; MUCOSITIS; POVIDONE; PRACTICE GUIDELINES AS TOPIC; PROBIOTICS; THROMBOSPONDINS; ZINC SULFATE;

EID: 84942245650     PISSN: 15233790     EISSN: 15346269     Source Type: Journal    
DOI: 10.1007/s11912-015-0474-9     Document Type: Review

References (80)

1. Stein A, Voigt W, Jordan K. Chemotherapy-induced diarrhea: pathophysiology, frequency and guideline-based management. Ther Adv Med Oncol. 2010;2(1):51–63.
2. Sonis ST. Oral mucositis in cancer therapy. J Support Oncol. 2004;2(6 Suppl 3):3–8.
3. Sonis ST. A biological approach to mucositis. J Support Oncol. 2004;2(1):21-32. discussion 35-6.
4. Sonis ST. The pathobiology of mucositis. Nat Rev Cancer. 2004;4(4):277–84. This paper describes in detail the currently accepted 5-phase pathophysiological model of mucositis.
5. Cirillo M et al. Clinician versus nurse symptom reporting using the National Cancer Institute-Common Terminology Criteria for Adverse Events during chemotherapy: results of a comparison based on patient’s self-reported questionnaire. Ann Oncol: Off J Eur Soc Med Oncol / ESMO. 2009;20(12):1929–35.
6. Sonis S. et al. Unanticipated frequency and consequences of regimen-related diarrhea in patients being treated with radiation or chemoradiation regimens for cancers of the head and neck or lung. Support Care Cancer: Off J Multinatl Assoc Support Care Cancer. 2014.
7. Foote M. The importance of planned dose of chemotherapy on time: do we need to change our clinical practice? Oncologist. 1998;3(5):365–8.
8. Di Fiore F, Van Cutsem E. Acute and long-term gastrointestinal consequences of chemotherapy. Best Pract Res Clin Gastroenterol. 2009;23(1):113–24.
9. Gibson RJ, Stringer AM. Chemotherapy-induced diarrhoea. Curr Opin Support Palliat Care. 2009;3(1):31–5.
10. Benson 3rd AB et al. Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol Off J Am Soc Clin Oncol. 2004;22(14):2918–26.
11. Carlotto A et al. 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(9):753–66.
12. Elting LS et al. The burdens of cancer therapy. Clinical and economic outcomes of chemotherapy-induced mucositis. Cancer. 2003;98(7):1531–9.
13. Lalla RV et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2014;120(10):1453–61. This paper reviewed the available literature and produced evidence based guidelines for the management of patients with mucositis, impacting clinical practice.
14. Keefe DM. Gastrointestinal mucositis: a new biological model. Support Care Cancer. 2004;12(1):6–9.
15. Gibson RJ et al. Irinotecan causes severe small intestinal damage, as well as colonic damage, in the rat with implanted breast cancer. J Gastroenterol Hepatol. 2003;18(9):1095–100.
16. Al-Dasooqi N et al. Emerging evidence on the pathobiology of mucositis. Support Care Cancer. 2013;21(11):3233–41. This paper provided recent and emerging research directions, to drive new clinical research.
17. Lalla RV, Ashbury FD. The MASCC/ISOO Mucositis Guidelines: dissemination and clinical impact. Support Care Cancer: Off J Multinatl Assoc Support Care Cancer. 2013;21(11):3161–3.
18. Davila M, Bresalier RS. Gastrointestinal complications of oncologic therapy. Nat Clin Pract Gastroenterol Hepatol. 2008;5(12):682–96.
19. Mehdipour M et al. A comparison between zinc sulfate and chlorhexidine gluconate mouthwashes in the prevention of chemotherapy-induced oral mucositis. Daru. 2011;19(1):71–3.
20. Arbabi-kalati F et al. 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(7):413–7.
21. Mansouri A et al. The effect of zinc sulfate in the prevention of high-dose chemotherapy-induced mucositis: a double-blind, randomized, placebo-controlled study. Hematol Oncol. 2012;30(1):22–6.
22. 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(1):343–55. This paper provided evidence based guidelines for the use of growth factors, including palifermin, in patients with mucositis.
23. 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(1):99–104.
24. 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(7):966–71.
25. Vadhan-Raj S et al. Single-dose palifermin prevents severe oral mucositis during multicycle chemotherapy in patients with cancer: a randomized trial. Ann Intern Med. 2010;153(6):358–67.
26. Bouma G, Strober W. The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol. 2003;3(7):521–33.
27. Shanahan F. Inflammatory bowel disease: immunodiagnostics, immunotherapeutics, and ecotherapeutics. Gastroenterology. 2001;120(3):622–35.
28. Holmberg J et al. EphB receptors coordinate migration and proliferation in the intestinal stem cell niche. Cell. 2006;125(6):1151–63.
29. 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(11), e8014.
30. 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(7):2331–6.
31. Abraham C, Cho JH. Inducing intestinal growth. N Engl J Med. 2005;353(21):2297–9.
32. Kim KA et al. Mitogenic influence of human R-spondin1 on the intestinal epithelium. Science. 2005;309(5738):1256–9.
33. Zhou WJ, Zhou WJ, et al. Induction of intestinal stem cells by R-spondin 1 and Slit2 augments chemoradioprotection. Nature. 2013;501(7465):107–11. This paper provided evidence of the protective role of R-spondin1 in chemoradiation-induced mucositis.
34. Kazemian A et al. Benzydamine for prophylaxis of radiation-induced oral mucositis in head and neck cancers: a double-blind placebo-controlled randomized clinical trial. Eur J Cancer Care (Engl). 2009;18(2):174–8.
35. Logan RM et al. Characterisation of mucosal changes in the alimentary tract following administration of irinotecan: implications for the pathobiology of mucositis. Cancer Chemother Pharmacol. 2008;62(1):33–41.
36. Keefe DM et al. Updated clinical practice guidelines for the prevention and treatment of mucositis. Cancer. 2007;109(5):820–31.
37. Sheibani KM et al. Efficacy of benzydamine oral rinse in prevention and management of radiation-induced oral mucositis: a double-blind placebo-controlled randomized clinical trial. Asia Pac J Clin Oncol. 2015;11(1):22–7. This paper provided evidence on the efficacy of benzydamine HCl in the prevention of radiation induced oral mucositis.
38. Epstein JB et al. Benzydamine HCl for prophylaxis of radiation-induced oral mucositis: results from a multicenter, randomized, double-blind, placebo-controlled clinical trial. Cancer. 2001;92(4):875–85.
39. Osterlund P et al. Lactobacillus supplementation for diarrhoea related to chemotherapy of colorectal cancer: a randomised study. Br J Cancer. 2007;97(8):1028–34.
40. Abd El-Atti S et al. Use of probiotics in the management of chemotherapy-induced diarrhea: a case study. JPEN J Parenter Enteral Nutr. 2009;33(5):569–70.
41. Mego M et al. Prevention of irinotecan induced diarrhea by probiotics: a randomized double blind, placebo controlled pilot study. Complement Ther Med. 2015;23(3):356–62.
42. Ciorba MA, Stenson WF. Probiotic therapy in radiation-induced intestinal injury and repair. Ann N Y Acad Sci. 2009;1165:190–4.
43. Ciorba MA. A gastroenterologist’s guide to probiotics. Clin Gastroenterol Hepatol. 2012;10(9):960–8.
44. Stringer AM et al. Irinotecan-induced mucositis manifesting as diarrhoea corresponds with an amended intestinal flora and mucin profile. Int J Exp Pathol. 2009;90(5):489–99.
45. Stringer AM et al. Chemotherapy-induced diarrhea is associated with changes in the luminal environment in the DA rat. Exp Biol Med (Maywood). 2007;232(1):96–106.
46. Bowen JM et al. VSL#3 probiotic treatment reduces chemotherapy-induced diarrhea and weight loss. Cancer Biol Ther. 2007;6(9):1449–54.
47. Prisciandaro LD et al. Probiotic factors partially improve parameters of 5-fluorouracil-induced intestinal mucositis in rats. Cancer Biol Ther. 2011;11(7):671–7.
48. Ciorba MA et al. Lactobacillus probiotic protects intestinal epithelium from radiation injury in a TLR-2/cyclo-oxygenase-2-dependent manner. Gut. 2012;61(6):829–38.
49. Wardill HR, Bowen JM, Gibson RJ. New pharmacotherapy options for chemotherapy-induced alimentary mucositis. Expert Opin Biol Ther. 2014;14(3):347–54.
50. Bossi P et al. Prevention and treatment of oral mucositis in patients with head and neck cancer treated with (chemo) radiation: report of an Italian survey. Support Care Cancer. 2014;22(7):1889–96.
51. Sorensen JB et al. Double-blind, placebo-controlled, randomized study of chlorhexidine prophylaxis for 5-fluorouracil-based chemotherapy-induced oral mucositis with nonblinded randomized comparison to oral cooling (cryotherapy) in gastrointestinal malignancies. Cancer. 2008;112(7):1600–6.
52. Orvain C et al. Miconazole mucoadhesive buccal tablet in high-dose therapy with autologous stem cell transplantation (HDT/ASCT)-induced mucositis. Support Care Cancer. 2015;23(2):359–64.
53. Lin JX et al. A comparison of dioctahedral smectite and iodine glycerin cream with topical mouth rinse in treatment of chemotherapy induced oral mucositis: a pilot study. Eur J Oncol Nurs. 2015;19(2):136–41.
54. Rao NG et al. Effect of prophylactic fluconazole on oral mucositis and candidiasis during radiation therapy for head-and-neck cancer. Pract Radiat Oncol. 2013;3(3):229–33.
55. Bensadoun RJ et al. Comparison of the efficacy and safety of miconazole 50-mg mucoadhesive buccal tablets with miconazole 500-mg gel in the treatment of oropharyngeal candidiasis: a prospective, randomized, single-blind, multicenter, comparative, phase III trial in patients treated with radiotherapy for head and neck cancer. Cancer. 2008;112(1):204–11.
56. Moslehi A et al. N-acetyl cysteine for prevention of oral mucositis in hematopoietic SCT: a double-blind, randomized, placebo-controlled trial. Bone Marrow Transplant. 2014;49(6):818–23.
57. Tsujimoto T et al. 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. 2015;33(1):33–9.
58. Chattopadhyay S et al. Role of oral glutamine in alleviation and prevention of radiation-induced oral mucositis: a prospective randomized study. South Asian J Cancer. 2014;3(1):8–12.
59. Gibson RJ et al. Systematic review of agents for the management of gastrointestinal mucositis in cancer patients. Support Care Cancer. 2013;21(1):313–26.
60. Blijlevens NM et al. A randomised, double-blinded, placebo-controlled, pilot study of parenteral glutamine for allogeneic stem cell transplant patients. Support Care Cancer. 2005;13(10):790–6.
61. Sornsuvit C et al. 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. 2008;36(6):1383–91.
62. Li Y et al. Oral glutamine ameliorates chemotherapy-induced changes of intestinal permeability and does not interfere with the antitumor effect of chemotherapy in patients with breast cancer: a prospective randomized trial. Tumori. 2006;92(5):396–401.
63. Leenstra JL 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 (NCCTG-N09C6 [Alliance]). J Clin Oncol. 2014;32(15):1571–7.
64. Epstein JB et al. Doxepin rinse for management of mucositis pain in patients with cancer: one week follow-up of topical therapy. Spec Care Dentist. 2008;28(2):73–7.
65. Guo SP et al. Transdermal fentanyl for pain due to chemoradiotherapy-induced oral mucositis in nasopharyngeal cancer patients: evaluating efficacy, safety, and improvement in quality of life. Drug Des Devel Ther. 2014;8:497–503.
66. Vokurka S et al. The effect of polyvinylpyrrolidone-sodium hyaluronate gel (Gelclair) on oral microbial colonization and pain control compared with other rinsing solutions in patients with oral mucositis after allogeneic stem cells transplantation. Med Sci Monit. 2011;17(10):CR572–6.
67. Velez I et al. MuGard, an oral mucoadhesive hydrogel, reduces the signs and symptoms of oral mucositis in patients with lichen planus: a double-blind, randomized, placebo-controlled pilot study. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014;118(6):657–64e2.
68. Hadjieva T et al. Treatment of oral mucositis pain following radiation therapy for head-and-neck cancer using a bioadhesive barrier-forming lipid solution. Support Care Cancer. 2014;22(6):1557–62.
69. Yarom N et al. Systematic review of natural agents for the management of oral mucositis in cancer patients. Support Care Cancer. 2013;21(11):3209–21.
70. Carvalho PA et al. Evaluation of low-level laser therapy in the prevention and treatment of radiation-induced mucositis: a double-blind randomized study in head and neck cancer patients. Oral Oncol. 2011;47(12):1176–81.
71. Silva GB et al. The prevention of induced oral mucositis with low-level laser therapy in bone marrow transplantation patients: a randomized clinical trial. Photomed Laser Surg. 2011;29(1):27–31.
72. Schubert MM et al. A phase III randomized double-blind placebo-controlled clinical trial to determine the efficacy of low level laser therapy for the prevention of oral mucositis in patients undergoing hematopoietic cell transplantation. Support Care Cancer. 2007;15(10):1145–54.
73. Cowen D et al. 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. 1997;38(4):697–703.
74. Jaguar GC et al. Low-energy laser therapy for prevention of oral mucositis in hematopoietic stem cell transplantation. Oral Dis. 2007;13(6):538–43.
75. Whelan HT et al. NASA light-emitting diodes for the prevention of oral mucositis in pediatric bone marrow transplant patients. J Clin Laser Med Surg. 2002;20(6):319–24.
76. Barasch A et al. Helium-neon laser effects on conditioning-induced oral mucositis in bone marrow transplantation patients. Cancer. 1995;76(12):2550–6.
77. Silva GB et al. Effect of low-level laser therapy on inflammatory mediator release during chemotherapy-induced oral mucositis: a randomized preliminary study. Lasers Med Sci. 2015;30(1):117–26.
78. Antunes HS et al. Low-power laser in the prevention of induced oral mucositis in bone marrow transplantation patients: a randomized trial. Blood. 2007;109(5):2250–5.
79. Bensadoun RJ, Nair RG. Low-level laser therapy in the prevention and treatment of cancer therapy-induced mucositis: 2012 state of the art based on literature review and meta-analysis. Curr Opin Oncol. 2012;24(4):363–70.
80. 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(1):333–41.