International Journal of Radiation Oncology * Biology * Physics
Volume 49, Issue 4 , Pages 917-930 , 15 March 2001

Prophylaxis of oral mucositis in irradiated head-and-neck cancer patients: a proposed classification scheme of interventions and meta-analysis of randomized controlled trials

  • Susan E Sutherland (D.D.S.)

      Affiliations

    • Department of Dentistry, Sunnybrook and Women’s College Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada, Toronto, Canada
    • Department of Dentistry, Toronto-Sunnybrook Regional Cancer Centre, Cancer Care Ontario, Toronto, Ontario, Canada
    • Corresponding Author InformationReprint requests to: Susan E. Sutherland, D.D.S., Department of Dentistry, Suite H126, Sunnybrook and Women’s College Health Sciences Centre, 2075 Bayview Ave., Toronto, Ontario, Canada M4N 3M5. Tel: (416) 480-4436; Fax: (416) 480-5757
  • ,
  • George P Browman, M.D.

      Affiliations

    • The Hamilton Regional Cancer Centre, Cancer Care Ontario, Hamilton, Ontario, Canada
    • Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada

,Accepted 25 September 2000.

References 

  1. Parsons J. The effect of radiation on normal tissues of the head and neck. In:  Million R,  Cassisi N editor. Management of head and neck cancer (A multidisciplinary approach). Philadelphia: JB Lippincott; 1994;p. 245–289
  2. Berger AM, Kilroy TJ. Oral complications. In:  De Vita V,  Hellman S,  Rosenberg S editor. Cancer (Principles and practice of oncology). 5th ed.. Philadelphia: Lippincott-Raven; 1997;p. 2714–2725
  3. Merlano M, Corvo R, Margarino G, et al.  Combined chemotherapy and radiation therapy in advanced inoperable squamous cell carcinoma of the head and neck (The final report of a randomized trial). Cancer. 1991;67:914–921
  4. Pinto LHJ, Canary PCV, Araujo CMM, et al.  Prospective randomized trial comparing hyperfractioned versus conventional radiotherapy in stages III and IV oropharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 1991;21:557–562
  5. Horiot JC, Le Fur R, N’Guyen T, et al.  Hyperfractionation versus conventional fractionation in oropharyngeal carcinoma (Final analysis of a randomized trial of the EORTC cooperative group of radiotherapy). Radiother Oncol. 1992;25:231–241
  6. Browman GP, Cripps C, Hodson DI, et al.  Placebo controlled randomized trial of infusion flourouracil during standard radiotherapy in locally advanced head and neck cancer. J Clin Oncol. 1994;12:2648–2653
  7. Peters LJ, Ang KK, Thames HD. Altered fractionation schedules. In:  Perez C,  Brady L editor. Principles and practice of radiation oncology. Philadelphia: JB Lippincott; 1992;p. 97–113
  8. Sonis S. Mucositis as a biological process (A new hypothesis for the development of chemotherapy-induced stomatotoxicity). Oral Oncol. 1998;34:39–43
  9. Sonis S, Edwards L, Lucey C. The biological basis for the attenuation of mucositis (The example of interleukin-11). Leukemia. 1999;13:831–834
  10. Verdi C. Cancer therapy and oral mucositis. An appraisal of drug prophylaxis. Drug Saf. 1993;185–195
  11. Marks J. Mucosal protectants and their application for head and neck chemoirradiation. Curr Opin Oncol. 1997;2:267–273
  12. Sonis ST, Clark J. Prevention and management of oral mucositis induced by antineoplastic therapy. Oncology. 1991;5:11–22
  13. Oxman A, Guyatt G. Guidelines for reading literature reviews. Can Med Assoc J. 1988;138:697–703
  14. Clarkson J, Worthington H, Eden O; et al. Oral care for patients with cancer treated with chemotherapy (excluding head and neck cancer). The Cochrane Database of Systematic Reviews 1998;3:
  15. Schulz KF, Chalmers I, Hayes RJ, et al.  Empirical evidence of bias (Dimensions of methodologic quality associated with estimates of treatment effects in controlled trials). JAMA. 1995;273:408–412
  16. Moher D, Pham B, Jones A, et al.  Does quality of reports of randomized trials affect estimates of intervention efficacy reported in meta-analysis?. Lancet. 1998;352:609–613
  17. Jadad AR, Moore RA, Carroll D, et al.  Assessing the quality of reports of randomized clinical trials (Is blinding necessary?). Control Clin Trials. 1996;17:1–12
  18. Parulekar W, Mackenzie R, Bjarnason G, et al.  Scoring oral mucositis. Oral Oncol. 1998;34:63–71
  19. Eisenberg E, Berkey C, Carr D, et al.  Efficacy and safety of non-steroidal antiinflammatory drugs for cancer pain (A meta-analysis). J Clin Oncol. 1994;12:2756–2765
  20. Moore A, McQuay H, Gavaghan D. Deriving dichotomous outcome measures from continuous data in randomised controlled trials of analgesics. Pain. 1996;66:229–237
  21. Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Ann Intern Med. 1997;127:820–826
  22. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–188
  23. Altmann S, Hoffmanns H. Cytoprotection with amifostine in radiotherapy or radio-chemotherapy of head and neck tumors. Strahlenther Onkol. 1999;175(Suppl. 4):30–33(in German)
  24. Buntzel J, Glatzel M, Schuth J, et al.  Cytoprotection with amifostine in the framework of radiochemotherapy in previously irradiated head and neck carcinoma. Strahlenther Onkol. 1999;175(Suppl. 4):37–40(in German)
  25. Vacha P, Marx M, Engel A, et al.  Side effects of postoperative radiochemotherapy with amifostine versus radiochemotherapy alone in head and neck tumors. Preliminary results of a prospective randomized trial. Strahlenther Onkol. 1999;175(Suppl. 4):18–22(in German)
  26. Scherlacher A, Beaufort-Spontin F. Radiotherapy of head-neck neoplasms (Prevention of inflammation of the mucosa by sucralfate treatment). Head Neck Oncol. 1990;38:24–28(in German)
  27. Oshitani T, Okada K, Kushima T, et al.  Clinical evaluation of sodium alginate on oral mucositis associated with radiotherapy. Nippon Gan Chiryo Gakkai Shi. 1990;25:1129–1137(in Japanese)
  28. Okutomi T, Kato Y, Ichihara H, et al.  Clinical effects of adjuvant therapy using Z-100 (Ancer 20 injection) for oral cancer—prevention of stomatitis and hematopoietic impairment. Gan To Kagaku Ryoho. 2000;27:65–71(in Japanese)
  29. Raletic-Savic J, Zivanovic A, Savic D. Use of prostin E2 in the treatment of stomatitis caused by radiotherapy. Arh Hig Rada Toksikol. 1991;42:295–301(Serbo-Croatian)
  30. Adamietz IA, Rahn R, Bottcher HD, et al.  Prevention of radiochemotherapy-induced mucositis. Value of the prophylactic mouth rinsing with PVP-iodine solution. Strahlenther Onkol. 1998;174:149–155(in German)
  31. Prada A, Lozza L, Moglia D, et al.  Effects of benzydamine on radio-polychemotherapeutic mucositis of the oral cavity. Int J Tissue React. 1985;7:237–239
  32. Prada A, Chiesa F. Effects of benzydamine on the oral mucositis during antineoplastic radiotherapy and/or intra-arterial chemotherapy. Int J Tissue React. 1987;9:115–119
  33. Lever SA, Dupuis LL, Chan HSL. Comparative evaluation of benzydamine oral rinse in children with anti-neoplastic-induced stomatitis. Drug Intell Clin Pharm. 1987;21:359–361
  34. Schubert MM, Newton RE. The use of benzydamine HCL for the management of cancer therapy-induced mucositis (Preliminary report of a multicentre study). Int J Tissue React. 1987;9:99–103
  35. Ferretti GA, Raybuld TP, Brown AT, et al.  Chlorhexidine prophylaxis for chemotherapy- and radiotherapy-induced stomatitis (A randomized double-blind trial). Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1990;69:331–338
  36. Allison RR, Vongtama V, Vaughan J, et al.  Symptomatic acute mucositis can be minimized or prophylaxed by the combination of sucralfate and fluconazole. Cancer Invest. 1995;13:16–22
  37. Meredith R, Salter M, Kim R, et al.  Sucralfate for radiation mucositis (Results of a double-blind randomized trial). Int J Radiat Oncol Biol Phys. 1997;37:275–279
  38. Kim JH, Chu F, Lakshmi V, et al.  A clinical study of benzydamine for the treatment of radiotherapy-induced mucositis of the oropharynx. Int J Tissue React. 1985;7:215–218
  39. Carnel SB, Blakeslee DB, Oswald SG, et al.  Treatment of radiation- and chemotherapy-induced stomatitis. Otolaryngol Head Neck Surg. 1990;102:326–330
  40. Tanner NSB, Stamford IF, Bennett A. Plasma prostaglandins in mucositis due to radiotherapy and chemotherapy for head and neck cancer. Br J Cancer. 1981;43:767–771
  41. Matejka M, Nell A, Kment G, et al.  Local benefits of prostaglandin E2 in radiochemotherapy-induced oral mucositis. Br J Oral Maxillofac Surg. 1990;28:89–91
  42. Wagner W, Radmard A, Schonekaes KG. A new administration schedule for amifostine as a radioprotector in cancer therapy. Anticancer Res. 1999;19:2281–2283
  43. Epstein JB, Stevenson-Moore P. Benzydamine hydrochloride in prevention and management of pain in oral mucositis associated with radiation therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1986;62:145–148
  44. Epstein JB. Benzydamine HCL in prevention of oropharyngeal mucositis in radiation therapy (Literature review and clinical study). Research Clin Forums. 1986;10:91–97
  45. Hanson W, Marks J, Reddy S, et al.  Protection from radiation-induced oral mucositis by misoprostal, a prostaglandin E1 analog (A placebo-controlled double-blind clinical trial). Am J Therapeutics. 1995;2:1–8
  46. McIlroy P. Radiation mucositis (A new approach to the prevention and treatment). Eur J Cancer Care. 1996;5:153–158
  47. Wagner W, Prott FJ, Schonekas KG. Amifostine (A radioprotector in locally advanced head and neck tumors). Oncol Rep. 1998;5:1255–1257
  48. Barker G, Loftus L, Cuddy P, et al.  The effects of sucralfate suspension and diphenhydramine syrup plus kaolin-pectin on radiotherapy-induced mucositis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1991;71:288–289
  49. Epstein J, Wong F. The efficacy of sucralfate suspension in the prevention of oral mucositis due to radiation therapy. Int J Radiat Oncol Biol Phys. 1994;28:693–698
  50. Makkonen TA, Bostrom P, Vilja P, et al.  Sucralfate mouth washing in the prevention of radiation-induced mucositis (A placebo-controlled double-blind randomized study). Int J Radiat Oncol Biol Phys. 1994;30:177–182
  51. Franzen L, Henriksson R, Littbrand B, et al.  Effects of sucralfate on mucositis during and following radiotherapy of malignancies in the head and neck region. A double-blind placebo-controlled study. Acta Oncol. 1995;34:219–223
  52. Cengiz M, Ozyar E, Ozturk D, et al.  Sucralfate in the prevention of radiation-induced oral mucositis. J Clin Gastroenterol. 1999;28:40–43
  53. Carter DL, Hebert ME, Smink K, et al.  Double blind randomized trial of sucralfate vs placebo during radical radiotherapy for head and neck cancers. Head Neck. 1999;21:760–766
  54. Pfeiffer P, Hansen O, Madsen EL, et al.  A prospective pilot study on the effect of sucralfate mouth-swishing in reducing stomatitis during radiotherapy of the oral cavity. Acta Oncol. 1990;29:471–473
  55. Lievens Y, Haustermans K, Van den Weyngaert D, et al.  Does sucralfate reduce the acute side-effects in head and neck cancer treated with radiotherapy? A double-blind randomized trial. Radiother Oncol. 1998;47:149–153
  56. Porteder H, Rausch E, Kment G, et al.  Local prostaglandin E2 in patients with oral malignancies undergoing chemo- and radiotherapy. Cranio-Max-Fac Surg. 1988;16:371–374
  57. Hanson WR, Marks JE, Reddy SP; et al. Protection from radiation-induced oral mucositis by a mouth rinse containing the prostaglandin E1 analog, Misoprostol: A placebo-controlled double blind clinical trial. In: Honn K, editor. Eicosanoids and other bioactive lipids in cancer, inflammation and radiation injury 2. New York: Plenum Press; 1997.
  58. Mills E. The modifying effect of beta-carotene on radiation and chemotherapy induced oral mucositis. Br J Cancer. 1988;57:416–417
  59. Maciejewski B, Zajusz A, Pilecki B, et al.  Acute mucositis in the stimulated oral mucosa of patients during radiotherapy for head and neck cancer. Radiother Oncol. 1991;22:7–11
  60. Dorr W, Jacubek A, Kummermehr J, et al.  Effects of stimulated repopulation on oral mucosa during conventional radiotherapy. Radiother Oncol. 1995;37:100–107
  61. Feber T. Management of mucositis in oral irradiation. Clin Oncol. 1996;8:106–111
  62. Mascarin M, Franchin G, Minatel M; et al. The effect of filgrastin (G-CSF) on mucositis in head and neck patients treated with hyperfractionated radiotherapy (RT). Annu Meet Am Soc Clin Oncol, 1996;15:739 (abstract).
  63. Masucci G, Fernberg JO, Hoglund-Ersin L; et al. Beneficial treatment of radiotherapy induced mucositis with rh-GM-CSF in patients with tumours of the oral cavity/oropharynx (Meeting Abstract). Abstr.167. In: Sixth International Congress of Anti-Cancer Treatment. Paris, France, 1996;83:Abstr.167, p. 83.
  64. Kannan V, Bapsy PP, Anantha N, et al.  Efficacy and safety of granulocyte macrophage colony-stimulating factor (GM-CSF) on the frequency and severity of radiation mucositis in patients with head and neck carcinoma. Int J Radiat Oncol Biol Phys. 1997;37:1005–1010
  65. Rosso M, Blasi G, Gherlone E, et al.  Effect of granulocyte-macrophage colony-stimulating factor on prevention of mucositis in head and neck cancer patients treated with chemo-radiotherapy. J Chemother. 1997;9:382–385
  66. Nicolatou O, Sotiropoulou-Lontou A, Skarlatos J, et al.  A pilot study of the effect of granulocyte-macrophage colony-stimulating factor on oral mucositis in head and neck cancer patients during x-radiation therapy (A preliminary report). Int J Radiat Oncol Biol Phys. 1998;42:551–556
  67. Rovirosa A, Ferre J, Biete A. Granulocyte macrophage-colony-stimulating factor mouthwashes heal oral ulcers during head and neck radiotherapy. Int J Radiat Oncol Biol Phys. 1998;41:747–754
  68. Makkonen TA, Minn H, Jekunen A, et al.  Granulocyte macrophage-colony stimulating factor (GM-CSF) and sucralfate in prevention of radiation-induced mucositis (a prospective randomized study). Int J Radiat Oncol Biol Phys. 2000;46:525–534
  69. Wagner W, Alfrink M, Haus U, et al.  Treatment of irradiation-induced mucositis with growth factors (rhGM-CSF) in patients with head and neck cancer. Anticancer Res. 1999;19:799–803
  70. Pillsbury H, Webster W, Rosenman J. Prostaglandin inhibitor and radiotherapy in advanced head and neck cancers. Arch Otolaryngol Head Neck Surg. 1986;112:552–553
  71. Samaranayake L, Robertson A, MacFarlane T, et al.  The effect of chlorhexidine and benzydamine mouthwashes on mucositis induced by therapeutic radiation. Clin Radiol. 1988;39:291–294
  72. Epstein JB, Stevenson-Moore P, Jackson S, et al.  Prevention of oral mucositis in radiation therapy (A controlled study with benzydamine hydrochloride rinse). Int J Radiat Oncol Biol Phys. 1989;16:1571–1575
  73. Mose S, Adamietz IA, Saran F, et al.  Can prophylactic application of immunoglobulin decrease radiotherapy-induced oral mucositis?. Am J Clin Oncol. 1997;20:407–411
  74. Spijkervet FKL, van Saene HKF, Panders AK, et al.  Effect of chlorhexidine rinsing on the oropharyngeal ecology in patients with head and neck cancer who have irradiation mucositis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1989;67:154–161
  75. Foote RL, Loprinzi CL, Frank AR, et al.  Randomized trial of a chlorhexidine mouthwash for alleviation of radiation-induced mucositis. J Clin Oncol. 1994;12:2630–2633
  76. Rahn R, Adamietz IA, Boettcher HD, et al.  Povidone-iodine to prevent mucositis in patients during anti-neoplastic radiochemotherapy. Dermatology. 1997;195:57–61
  77. Spijkervet FK, van Saene HK, van Saene JJ, et al.  Mucositis prevention by selective elimination of oral flora in irradiated head and neck cancer patients. J Oral Pathol Med. 1990;19:486–489
  78. Kaanders JH, Pop LA, Uitterhoeve RJ; et al. Prevention of irradiation mucositis in the oral cavity and oropharynx by PTA-lozenges. In: 35th Annual ASTRO Meeting. New Orleans: Pergamon Press, 1993:253.
  79. Matthews RH, Ercal N. Prevention of mucositis in irradiated head and neck cancer patients. J Exp Ther Oncol. 1996;1:135–138
  80. Oguchi M, Shikama N, Sasaki S, et al.  Mucosa-adhesive water-soluble polymer film for treatment of acute radiation-induced oral mucositis. Int J Radiat Oncol Biol Phys. 1998;40:1033–1037
  81. Symonds RP, McIlroy P, Khorrami J, et al.  The reduction of radiation mucositis by selective decontamination antibiotic pastilles (A placebo-controlled double-blind trial). Br J Cancer. 1996;74:312–317
  82. Okuno SH, Foote RL, Loprinzi CL, et al.  A randomized trial of a non-absorbable antibiotic lozenge given to alleviate radiation-induced mucositis. Cancer. 1997;79:2193–2199
  83. Peters K, Mucke R, Hamann D, et al.  Supportive use of amifostine in patients with head and neck tumors undergoing radio-chemotherapy. Is it possible to limit the duration of the application of amifostine?. Strahlenther Onkol. 1999;175(Suppl. 4):23–26
  84. Schneider SB, Nishimura RD, Zimmerman RP, et al.  Filgrastim (r-metHuG-CSF) and its potential use in the reduction of radiation-induced oropharyngeal mucositis (An interim look at a randomized, double-blind, placebo-controlled trial). Cytokines Cell Mol Ther. 1999;5:175–180
  85. Trog D, Bank P, Wendt TG, et al.  Daily amifostine given concomitantly to chemoradiation in head and neck cancer. A pilot study. Strahlenther Onkol. 1999;175:444–449
  86. Schonekas KG, Wagner W, Prott FJ. Amifostine—a radioprotector in locally advanced head and neck tumors. Strahlenther Onkol. 1999;175(Suppl. 4):27–29
  87. Buntzel J, Kuttner K, Frohlich D, et al.  Selective cytoprotection with amifostine in concurrent radiochemotherapy for head and neck cancer. Ann Oncol. 1998;9:505–509
  88. Bensadoun RJ, Franquin JC, Ciais G, et al.  Low-energy He/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. 1999;7:244–252
  89. Huang EY, Leung SW, Wang CJ, et al.  Oral glutamine to alleviate radiation-induced oral mucositis (a pilot randomized trial). Int J Radiat Oncol Biol Phys. 2000;46:535–539
  90. Pfeiffer P, Madsen E, Hansen O, et al.  Effect of prophylactic sucralfate on stomatitis induced by cancer chemotherapy. Acta Oncol. 1989;29:171–173
  91. NCIC. A double-blind phase III prospective randomized study of Bacitracin, Clotrimazole, Gentamicin (BCOG) lozenges versus placebo lozenges for radiation-associated mucositis in head and neck cancer. In. Canada: Canada, NCIC CTG TRIAL: HN:2 (Multi-centre), 1997.
  92. Egger M, Smith G, Phillips A. Meta-analysis (Principles and procedures). BMJ. 1997;315:1533–1537
  93. Cook D, Sackett D, Spitzer W. Methodologic guidelines for systematic reviews of randomized controlled trials in health care from the Potsdam Consultation on meta-analysis. J Clin Epidemiol. 1995;48:167–171
  94. Miller T, Jacobson E. Gastrointestinal cytoprotection by prostaglandins. Gut. 1979;20:75–87
  95. Nagashima R. Mechanisms of action of sucralfate. J Clin Gastroenterol. 1981;3:117–127
  96. Tarnawski A, Hollander D, Krause W, et al.  Does sucralfate affect the normal gastric mucosa? Histologic, ultrastructural and functional assessment in the rat. Gastroenterology. 1986;90:893–905
  97. Ligumsky M, Karmeli F, Rachmilewitz D. Sucralfate stimulation of gastric PGE2 synthesis—possible mechanism to explain its effective cytoprotective properties. (Abstr) Gastroenterology. 1984;86:1164
  98. Robert A. Cytoprotection by prostaglandins. Gastroenterology. 1979;77:761–767
  99. Conley B, Ord R. Current status of retinoids in chemoprevention of oral squamous cell carcinoma (An overview). J Craniomaxillofac Surg. 1996;24:339–345
  100. Girod S, Pfahl M. Retinoid actions and implications for prevention and therapy of oral cancer. Int J Oral Maxillofac Surg. 1996;25:69–73
  101. Tombes M, Gallucci B. The effects of hydrogen peroxide rinses on the normal oral mucosa. Nurs Res. 1993;42:332–337
  102. Groopman JE, Molina JM, Scadden DT. Hematopoietic growth factors (Biology and clinical applications). N Engl J Med. 1989;321:1449–1459
  103. Northway MG, Libshitz HI, Osborne BM, et al.  Radiation esophagitis in the opossum (Radioprotection with indomethacin). Gastroenterology. 1980;78:883–892
  104. Segre G, Hammarstrom S. Aspects of the mechanism of action of benzydamine. Int J Tissue React. 1985;7:187–193
  105. Rice D, Gill G. The effect of irradiation upon the bacterial flora in patients with head and neck cancer. Laryngoscope. 1979;84:1839–1841
  106. Bernhoft C, Skaug N. Oral findings in irradiated edentulous patients. Int J Oral Surg. 1985;14:416–427
  107. Sonis ST, Eilers JP, Epstein JB; et al. Validation of a new scoring system for the assessment of clinical trial research of oral mucositis induced by radiation or chemotherapy. Mucositis Study Group. Cancer 1999;85:2103–2113.
  108. Felson D. Bias in meta-analytic research. J Clin Epidemiol. 1992;45:885–892
  109. Gregoire G, Derderian F, Le Lorier J. Selecting the language of the publications included in a meta-analysis (Is there a tower of babel bias?). J Clin Epidemiol. 1995;48:159–163
  110. Capizzi RL. The preclinical basis for broad-spectrum selective cytoprotection of normal tissues from cytotoxic therapies by amifostine. Semin Oncol. 1999;26:3–21
  111. Santini V, Giles FJ. The potential of amifostine (From cytoprotectant to therapeutic agent). Haematologica. 1999;84:1035–1042
  112. Klimberg VS, Souba WW, Dolson DJ, et al.  Prophylactic glutamine protects the intestinal mucosa from radiation injury. Cancer. 1990;66:62–68
  113. Abergel RP, Lyons RF, Castel JC, et al.  Biostimulation of wound healing by lasers (Experimental approaches in animal models and in fibroblast cultures). J Dermatol Surg Oncol. 1987;13:127–133
  114. Lyons RF, Abergel RP, White RA, et al.  Biostimulation of wound healing in vivo by a helium-neon laser. Ann Plast Surg. 1987;18:47–50
  115. Abergel RP, Meeker CA, Lam TS, et al.  Control of connective tissue metabolism by lasers (Recent developments and future prospects). J Am Acad Dermatol. 1984;11:1142–1150
  116. Masucci G. New clinical applications of granulocyte-macrophage colony-stimulating factor. Med Oncol. 1996;13:149–154
  117. Addy M, Wright R. Comparison of the in vivo and in vitro antibacterial properties of povidone-iodine and chlorhexidine gluconate mouthrinses. J Clin Periodontol. 1978;5:198–205
  118. Walker C. Microbiological effects of mouthrinses containing antimicrobials. J Clin Periodontol. 1988;15:499–505
  119. Rolla G, Loe H, Schiott C. Retention of chlorhexidine in the human oral cavity. Arch Oral Biol. 1971;16:1109–1116
  120. Martin M. Irradiation mucositis: A reappraisal. Eur J Cancer B Oral Oncol 1993;29B:1–2.

PII: S0360-3016(00)01456-5

doi: 10.1016/S0360-3016(00)01456-5

International Journal of Radiation Oncology * Biology * Physics
Volume 49, Issue 4 , Pages 917-930 , 15 March 2001