Head and Neck TumorsHead and Neck TumorsОпухоли головы и шеи2222-14682411-4634Publishing House ABV Press42010.17650/2222-1468-2019-9-3-29-37DIAGNOSIS AND TREATMENT OF HEAD AND NECK TUMORSДИАГНОСТИКА И ЛЕЧЕНИЕ ОПУХОЛЕЙ ГОЛОВЫ И ШЕИRole of hyaluronic acid in the prevention and treatment of radiation-induced oropharyngeal mucositisРоль препаратов гиалуроновой кислоты в профилактике и лечении лучевого мукозита полости рта и ротоглоткиhttps://orcid.org/0000-0002-6851-9867AlymovYu. V.АлымовЮ. В.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

Юрий Владимирович Алымов 

115478 Москва, Каширское шоссе, 24

allmedperevod@gmail.comhttps://orcid.org/0000-0003-1255-5700MudunovА. М.МудуновА. М.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24

https://orcid.org/0000-0002-6835-5567AlievaS. B.АлиеваС. Б.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24

https://orcid.org/0000-0002-6796-0968IgnatovaА. V.ИгнатоваА. В.
Russian Federation

Bld. 1, 2 / 1 Barrikadnaya St., Moscow 125993; 6 Miklukho-Maklaya St., Moscow 117198

125993 Москва, ул. Баррикадная, 2 / 1, стр. 1; 117198 Москва, ул. Миклухо-Маклая, 6

KaledinR. R.КалединР. Р.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24

https://orcid.org/0000-0003-4068-7698AvanesovА. М.АванесовА. М.
Russian Federation

6 Miklukho-Maklaya St., Moscow 117198; 86 Profsoyuznaya St., Moscow 117997

117198 Москва, ул. Миклухо-Маклая, 6; 117997 Москва, ул. Профсоюзная, 86

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н. Н. Блохина» Минздрава РоссииRussian Medical Academy of Continuing Professional Education, Ministry of Health of RussiaФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава РоссииRUDN UniversityФГАОУ ВО «Российский университет дружбы народов»Russian Scientific Center of RoentgenoradiologyФГБУ «Российский научный центр рентгенорадиологии» Минздрава России311020199329373110201931102019Copyright ©; 2019, Alymov Y.V., Mudunov А.М., Alieva S.B., Ignatova А.V., Kaledin R.R., Avanesov А.М.Copyright ©; 2019, Алымов Ю.В., Мудунов А.М., Алиева С.Б., Игнатова А.В., Каледин Р.Р., Аванесов А.М.2019Alymov Y.V., Mudunov А.М., Alieva S.B., Ignatova А.V., Kaledin R.R., Avanesov А.М.Алымов Ю.В., Мудунов А.М., Алиева С.Б., Игнатова А.В., Каледин Р.Р., Аванесов А.М.https://creativecommons.org/licenses/by/4.0https://ogsh.abvpress.ru/jour/article/view/420

One of the earliest and most common adverse events of radiotherapy in patients with oropharyngeal cancers is mucositis. Radiation-induced mucositis significantly impairs the quality of life, patient compliance, and sometimes even long-term treatment outcomes. Currently, there is a wide range of drugs and techniques for the prevention and treatment of this complication. Nevertheless, these methods are not always highly effective and often have their own adverse events; therefore, the search for a universal method still continues. The present review aims to analyze the efficacy of hyaluronic acid in the prevention and treatment of oropharyngeal mucositis.

Один из ранних и наиболее частых побочных эффектов лучевой терапии у пациентов со злокачественными опухолями орофарингеальной зоны – мукозит. Лучевой мукозит существенно ухудшает качество жизни, комплаенс пациентов и в ряде случаев отдаленные результаты лечения. Сегодня существует большой спектр препаратов и методик для профилактики и лечения данного осложнения. Тем не менее эти средства и методики также имеют побочные эффекты и не являются высокоэффективными, в связи с чем продолжается поиск универсального средства. Цель данного обзора – анализ научной литературы, посвященной изучению эффективности препаратов на основе гиалуроновой кислоты в профилактике и лечении мукозита орофарингеальной зоны.

mucositishyaluronic acidoral cavityoropharynxradiotherapychemoradiotherapyмукозитгиалуроновая кислотаполость ртаротоглоткалучевая терапияхимиолучевая терапияThe article was published with the support of RIVIERA BIOTECH.Статья опубликована при поддержке компании «РИВЬЕРА БИОТЕК».Globocan 2018 Latest global cancer data. Available at: https://www.iarc.fr/infographics/globocan-2018-latest-global-cancer-data/.Malignant tumors in Russia in 2017 (morbidity and mortality). Ed. by A.D. Kaprin, V.V. Starinsky, G.V. Petrova. Moscow: MNIOI im. P.A. Gertzena, 2018. Pp. 11, 12, 17. (In Russ.) Available at: http://www.oncology.ru/service/statistics/malignant_tumors/2017.pdf].Злокачественные новообразования в России в 2017 году(заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М.: МНИОИ им. П.А. Герцена, 2018. С. 11, 12, 17. Доступно по: http://www.oncology.ru/service/statistics/malignant_tumors/2017.pdf.Pivot X., Felip E., ESMO Guidelines Working Group. Squamous cell carcinoma of the head and neck: ESMO clinical Recommendations for diagnosis, treatment and follow-up. Ann Оncol 2008;19 Suppl 2:ii79–80. DOI: 10.1093/annonc/mdn097.Matyakin E.G., Podvyaznikov S.O. Oncology: handbook for physicians. Ed. by I.V. Poddubnaya. Moscow: MEDpressinform, 2009. Pp. 162, 163. (In Russ.)Матякин Е.Г., Подвязников С.О. Онкология: справочник практического врача. Под ред. И.В. Поддубной. М.: МЕДпресс-информ, 2009. С. 162, 163.Therapeutic radio lo gy: national guidelines. Ed. by A.D. Kaprin, Yu.S. Mardynsky. Moscow: GeotarMedia, 2018. 704 p. (In Russ.)Терапевтическая радиология: национальное руководство. Под ред. А.Д. Каприна, Ю.С. Мардынского. М.: ГэотарМедиа, 2018. 704 с.Barnett G.C., West C.M., Dunning A.M. et al. Normal tissue reactions to radiotherapy: towards tailoring treatment dose by genotype. Nat Rev Cancer 2009;9(2):134–42. DOI: 10.1038/nrc2587.Stone H.B., Coleman C.N., Anscher M.S., McBride W.H. Effects of radiation on normal tissue: consequences and mechanisms. Lancet Oncol 2003;4(9):529–36.Sokurenko V.P., Korytova L.I., Bochkareva T.N. The experience of conformal radiation therapy treatment of patients with oropharyngeal cancer. Meditsinskaya fizika = Medical Physics 2009;(1):39–45. (In Russ.)Сокуренко В.П., Корытова Л.И., Бочкарева Т.Н. Опыт конформной лу- чевой терапии больных с опухолями орофарингеальной зоны. Медицинская физика 2009;(1):39–45.Li Y., Taylor J.M., Ten Haken R.K., Eisbruch A. The impact of dose on parotid salivary recovery in head and neck cancer patients treated with radiation therapy. Int J Radiat Oncol Biol Phys 2007;67(3):660–9. DOI: 10.1016/j.ijrobp.2006.09.021.Rosenthal D.I., Trotti A. Strategies for managing radiation-induced mucositis in head and neck cancer. Semin Radiat Oncol 2009;19(1):29–34. DOI: 10.1016/j.semradonc.2008.09.006.Campos M.I., Campos C.N., Aarestrup F.M., Aarestrup B.J. Oral mucositis in cancer treatment: natural history, prevention and treatment. Mol Clin Oncol 2014;2(3):337–40. DOI: 10.3892/mco.2014.253.Otmani N. Oral and maxillofacial side effects of radiation therapy on children. J Can Dent Assoc 2007;73(3):257–61.Redding S.W. Cancer therapy-related oral mucositis. J Dent Educ 2005;69(8):919–29.Barasch A., Coke J.M. Cancer therapeutics: an update on its effects on oral health. Periodontol 2000 2007;44:44–54. DOI: 10.1111/j.1600-0757.2006.00199.x.Sonis S.T. The pathobiology of mucositis. Nat Rev Cancer 2004;4(4):277–84. DOI: 10.1038/nrc1318.Handschel J., Prott F.J., Sunderkötter C. et al. Irradiation induces increase of adhesion molecules and accumulation of beta2-integrin-expressing cells in humans. Int J Radiat Oncol Biol Phys 1999;45(2):475–81. DOI: 10.1016/s0360-3016(99)00202-3.Hancock P.J., Epstein J.B., Sadler G.R. Oral and dental management related to radiation therapy for head and neck cancer. J Can Dent Assoc 2003;69(9):585–90.Köstler W.J., Hejna M., Wenzel C., Zielinski C.C. Oral mucositis complicating chemotherapy and/or radiotherapy: options for prevention and treatment. CA Cancer J Clin 2001;51(5):290–315.Mallick S., Benson R., Rath G.K. Radiation induced oral mucositis: a review of current literature on prevention and management. Eur Arch Otorhinolaryngol 2016;273(9):2285–93. DOI 10.1007/s00405-015-3694-6.Overgaard J., Hjelm-Hansen M., Johansen L.V., Andersen A.P. Comparison of conventional and split-course radiotherapy as primary treatment in carcinoma of the larynx. Acta Oncol 1988;27(2):147–52. DOI: 10.3109/02841868809090334.Van den Bogaert W., Van der Leest A., Rijnders A. et al. Does tumor control decrease by prolonging overall treatment time or interrupting treatment in laryngeal cancer? Radiother Oncol 1995;36(3):177–82. DOI: 10.1016/0167-8140(95)01597-a.Maciejewski B., Preuss-Bayer G., Trott K.R. The influence of the number of fractions and of OTT on local control and late complication rate in squamous cell carcinoma of the larynx. Int J Radiat Oncol Biol Phys 1983;9(3):321–8. DOI: 10.1016/0360-3016(83)90290-0.Maciejewski B., Withers H.R., Taylor J.M., Hliniak A. Dose fractionation and regeneration in radiotherapy for cancer of the oral cavity and oropharynx: tumor dose-response and repopulation. Int J Radiat Oncol Biol Phys 1989;16(3):831–43. DOI: 10.1016/0360-3016(89)90503-8.Fowler J.F., Lindstrom M.J. Loss of local control with prolongation in radiotherapy. Int J Radiat Oncol Biol Phys 1992;23(2):457–67. DOI: 10.1016/0360-3016(92)90768-d.Yao J.J., Jin Y.N., Wang S.Y. et al. The detrimental effects of radiotherapy interruption on local control after concurrent chemoradiotherapy for advanced T-stage nasopharyngeal carcinoma: an observational, prospective analysis. BMC Cancer 2018;18(1):740. DOI: 10.1186/s12885-018-4495-2.Atkins E.D., Sheehan J.K. Structure for hyaluronic acid. Nat New Biol 1972;235(60):253–4. DOI: 10.1038/newbio235253a0.Ialenti A., Di Rosa M. Hyaluronic acid modulates acute and chronic inflammation. Agents Actions 1994;43(1–2): 44–7. DOI: 10.1007/bf02005763.Fraser J.R., Laurent T.C., Laurent U.B. Hyaluronan: its nature, distribution, functions and turnover. J Intern Med 1997;242(1):27–33. DOI: 10.1046/j.1365-2796.1997.00170.x.Necas J., Bartosikova L., Brauner P., Kolar J. Hyaluronic acid (hyaluronan): a review. Vet Med 2008;53:397–411.Uttara B., Singh A.V., Zamboni P., Mahajan R.T. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol 2009;7(1):65–74. DOI: 10.2174/157015909787602823.Wolny P.M., Banerji S., Gounou C. et al. Analysis of CD44-hyaluronan interactions in an artificial membrane system: insights into the distinct binding properties of high and low molecular weight hyaluronan. J Biol Chem 2010;285(39):30170–80. DOI: 10.1074/jbc.M110.137562.Termeer C., Benedix F., Sleeman J. et al. Oligosaccharides of hyaluronan activate dendritic cells via toll-like receptor 4. J Exp Med 2002;195(1):99–111.Forteza R., Lieb T., Aoki T. et al. Hyaluronan serves a novel role in airway mucosal host defense. FASEB J 2001;15(12):2179–86. DOI: 10.1096/fj.01-0036com.Jentsch H., Pomowski R., Kundt G., Gocke R. Treatment of gingivitis with hyaluronan. J Clin Periodontol 2003;30(2):159–64. DOI: 10.1034/j.1600-051x.2003.300203.x.Nolan A., Baillie C., Badminton J. et al. The efficacy of topical hyaluronic acid in the management of recurrent aphthous ulceration. J Oral Pathol Med 2006;35(8):461–5. DOI: 10.1111/j.1600-0714.2006.00433.x.Rodriguez-Merchan E.C. Intra-articular injections of hyaluronic acid and other drugs in the knee joint. HSS J 2013;9(2):180–2. DOI: 10.1007/s11420-012-9320-x.Migliore A., Granata M. Intra-articular use of hyaluronic acid in the treatment of osteoarthritis. Clin Interv Aging 2008;3(2):365–9.Ciofalo A., Zambetti G., Altissimi G. et al. Pathological and cytological changes of the nasal mucosa in acute rhinosinusitis: the role of hyaluronic acid as supportive therapy. Eur Rev Med Pharmacol Sci 2017;21(19):4411–8.Migliore A., Massafra U., Frediani B. et al. HyalOne in the treatment of symptomatic hip OA – data from the ANTIAGE register: seven years of observation. Eur Rev Med Pharmacol Sci 2017;21(7):1635–44.Caporossi A., Baiocchi S., Sforzi C., Frezzotti R. Healon GV versus Healon in demanding cataract surgery. J Cataract Refract Surg 1995;21(6):710–3. DOI: 10.1016/s0886-3350(13)80572-x.Cirillo N., Vicidomini A., McCullough M. et al. A hyaluronic acid-based compound inhibits fibroblast senescence induced by oxidative stress in vitro and prevents oral mucositis in vivo. J Cell Physiol 2015;230(7):1421–9. DOI: 10.1002/jcp.24908.Di Franco R., Muto M., Ravo V. et al. Oral mucositis related to radiotherapy for head and neck cancer: evaluation of the effectiveness of a new anti-inflamma tory product containing verbascoside, polyvinylpyrrolidone, hyaluronic acid (Mucosyte). Pharm Anal Acta 2014;5:312. DOI: 10.4172/2153-2435.1000312.Colella G., Cannavale R., Vicidomini A. et al. Efficacy of a spray compound containing a pool of collagen precursor synthetic aminoacids (L-proline, L-leucine, L-lysine and glycine) combined with sodium hyaluronate to manage chemo/radiotherapy-induced oral mucositis: preliminary data of an open clinical trial. Int J Immunopathol Pharmacol 2010;23(1):143–51. DOI: 10.1177/039463201002300113.Peterman A., Cella D., Glandon G. et al. Mucositis in head and neck cancer: economic and quality-of-Iife outcomes. J Natl Cancer Inst Monogr 2001;(29):45–51. DOI: 10.1093/oxfordjournals.jncimonographs.a003440.Lalla R.V., Bowen J., Barasch A. et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 2014;120(10):1453–61. DOI: 10.1002/cncr.28592.Maria O.M., Eliopoulos N., Muanza T. Radiation-induced oral mucositis. Front Oncol 2017;7:89. DOI: 10.3389/fonc.2017.00089.Praetorius N.P., Mandal T.K. Alternate delivery route for amifostine as a radio-/chemo-protecting agent. J Pharm Pharmacol 2008;60(7):809–15. DOI: 10.1211/jpp.60.7.0001.Masucci G., Broman P., Kelly C. et al. Therapeutic efficacy by recombinant human granulocyte/monocyte-colony stimulating factor on mucositis occurring in patients with oral and oropharynx tumors treated with curative radiotherapy: a multicenter open randomized phase III study. Med Oncol 2005;22(3):247–56. DOI: 10.1385/MO:22:3:247.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(20):2815–20. DOI: 10.1200/JCO.2010.32.4103.Tsujimoto T., Yamamoto Y., Wasa M. 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. DOI: 10.3892/or.2014.3564.Chattopadhyay S., Saha A., Azam M. 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. DOI: 10.4103/2278-330X.126501.Mills E.E. The modifying effect of betacarotene on radiation and radiotherapy and chemotherapy induced oral mucositis. Br J Cancer 1988;57(4):416–7. DOI: 10.1038/bjc.1988.94.Mose S., Adamietz I.A., Saran F. et al. Can prophylactic application of immunoglobulin decrease radiotherapy-induced oral mucositis? Am J Clin Oncol 1997;20(4):407–11. DOI: 10.1097/00000421-199708000-00018.Labar B., Mrsić M., Pavletić Z. et al. Prostaglandin E2 for prophylaxis of oral mucositis following BMT. Bone Marrow Transplant 1993;11(5):379–82.Kührer I., Kuzmits R., Linkesch W., Ludwig H. Topical PGE2 enhances healing of hemotherapy-associated mucosal lesions. Lancet 1986;1(8481):623.LeVeque F.G., Parzuchowski J.B., Farinacci G.C. et al. Clinical evaluation of MGI 209, an anesthetic, film-forming agent for relief from painful oral ulcers associated with chemotherapy. J Clin Oncol 1992;10(12):1963–8. DOI: 10.1200/JCO.1992.10.12.1963.Sarvizadeh M., Hemati S., Meidani M. et al. Morphine mouthwash for the management of oral mucositis in patients with head and neck cancer. Adv Biomed Res 2015;4:44. DOI: 10.4103/2277-9175.151254.Dos Reis P.E., Ciol M.A., de Melo N.S. et al. Сhamomile infusion cryotherapy to prevent oral mucositis induced by chemotherapy: a pilot study. Support Care Cancer 2016;24:4393–8.Cohen G., Elad S., Or R. et al. The use of tretinoin as oral mucositis prophylaxis in bone marrow transplantation patients: a preliminary study. Oral Dis 1997;3(4):243–6.Ferreira P.R., Fleck J.F., Diehl A. et al. Protective effect of alpha-tocopherol in head and neck cancer radiation-induced mucositis: a double-blind randomized trial. Head Neck 2004;26(4):313–21. DOI: 10.1002/hed.10382.Nicolatou-Galitis O., Velegraki A., Sotiropoulou-Lontou A. et al. Effect of fluconazole antifungal prophylaxis on oral mucositis in head and neck cancer patients receiving radiotherapy. Support Care Cancer 2006;14(1):44–51. DOI: 10.1007/s00520-005-0835-2.Prelack M.S., Patterson K.R., Berger J.R. Varicella zoster virus rhombencephalomyelitis following radiation therapy for oropharyngeal carcinoma. J Clin Neurosci 2016;25:164–6. DOI: 10.1016/j.jocn.2015.09.009.Kielty C.M., Whittaker S.P., Grant M.E., Shuttleworth C.A. Type VI collagen microfibrils: evidence for a structural association with hyaluronan. J Cell Biol 1992;118(4): 979–90. DOI: 10.1083/jcb.118.4.979.Rooney P., Kumar S. Inverse relationship between hyaluronan and collagens in development and angiogenesis. Differentiation 1993;54(1):1–9.Buchsel P.C. Polyvinylpyrrolidone-sodium hyaluronate gel (Gelclair): a bioadherent oral gel for the treatment of oral mucositis and other painful oral lesions. Expert Opin Drug Metab Toxicol 2008;4(11): 1449–54. DOI: 10.1517/17425255.4.11.1449.Soldati D., Rahm F., Pasche P. Mucosal wound healing after nasal surgery. A controlled clinical trial on the efficacy of hyaluronic acid containing cream. Drugs Exp Clin Res 1999;25(6):253–61.Cantor J.O., Nadkami P.P. Hyaluronan: the Jekyll and Hyde molecule. Inflamm Allergy Drug Targets 2006;5(4):257–60.