Palifermin is a human growth factor approved by the U.S. Food and Drug Administration (FDA) to decrease the incidence and duration of severe OM among patients with hematologic malignancies undergoing conditioning with high-dose chemotherapy and total body irradiation for autologous stem cell transplant.14 In its pivotal trial, palifermin significantly reduced the duration of severe OM compared with placebo (3 vs 9 days; P < .001) and reduced the incidence of grade 4 OM by 42% (P < .001).15 Palifermin also reduced patient-reported mouth soreness, opioid use, and need for total parenteral nutrition.

LLLT, which uses 650 nm with a power of 40 mW, and tissue energy dose of 2 J/cm2, is recommended for patients receiving high-dose chemotherapy conditioning for HSCT, with or without irradiation.3 LLLT may also benefit patients with head and neck cancer undergoing radiation without concomitant chemotherapy; there is insufficient evidence for patients receiving combination radiation and chemotherapy. A meta-analysis published in 2017 that included 57 studies and 5261 patients receiving radiation for head and neck cancer found that LLLT resulted in better outcomes compared with other preventative measures for preventing severe OM.16

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Nonsteroidal anti-inflammatory benzydamine hydrochloride–containing mouthwash reduces the production of proinflammatory cytokines, and is recommended for patients with head and neck cancers who receive a moderate dose radiation therapy (up to 50 Gy) without concomitant chemotherapy.3 There was conflicting evidence for the use of amifostine mouthwash, and there was insufficient evidence for other agents including diphenhydramine, prostaglandin E2, immunoglobulins, corticosteroids, indomethacin, azelastine, mesalazine, aspirin, orgotein, flurbiprofen, histamine, colchicine, and placentrex. Mucosal coating agent–containing lozenges and mouthwash are not recommended for the prevention of OM.

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Antimicrobial mouthwashes or lozenges are currently not recommended for the prevention of OM.3 However, some studies have shown that lozenges containing polymyxin-E or tobramycin and mouthwash containing ciprofloxacin or ampicillin may prevent severe OM.4 In addition, the FDA recently granted fast track designation to brilacidin-OM, which is an oral rinse that contains the antimicrobial agent defensin-mimetic brilacidin.4 A novel agent, the short synthetic peptide dusquetide, which modulates the immune response to microbial insult and accelerates healing of damaged tissue, also has a fast tract designation and is currently being evaluated in a phase 3 trial.17

Zinc lozenges may benefit patients with head and neck cancer undergoing radiation or chemoradiation.3 There was insufficient or conflicting evidence regarding other natural remedies including glutamine, vitamin A, vitamin E, honey, aloe vera, chamomile, Chinese medicine, and manuka oil.

Pain Control

OM is very painful and frequently requires opioid analgesics. Patient-controlled morphine is recommended for patients with OM undergoing high-dose chemotherapy conditioning for HSCT. Mouthwash containing 0.2% morphine is suggested to treat pain associated with OM among patients with head and neck cancer receiving chemoradiation, and 0.5% doxepin mouthwash can be used for any patient with OM.

Other options for pain control, which are not discussed by the MASCC/ISOO guideline, include a 2% lidocaine viscous gel before meals, dyclonine hydrochloride, benzocaine gel or lozenges, and magic mouthwash (which contains lidocaine).4

Other Interventions

Other supportive interventions can help manage or alleviate symptoms associated with OM. For example, over-the-counter saliva substitutes as a spray or gel can help relieve mucosal dryness in mild cases of OM.4

References

  1. Peterson DE, Boers-Doets CB, Bensadoun RJ, Herrstedt J; ESMO Guidelines Committee. Management of oral and gastrointestinal mucosal injury: ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up. Ann Oncol. 2015;26 (supl 5):v139-v151. doi:10.1093/annonc/mdv202
  2. Chen SC, Lai YH, Huang BS, Lin CY, Fan KH, Chang JT. Changes and predictors of radiation-induced oral mucositis in patients with oral cavity cancer during active treatment. Eur J Oncol Nurs. 2015;19:214-9. doi: 10.1016/j.ejon.2014.12.001
  3. 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. doi: 10.1002/cncr.28592
  4. Maria OM, Eliopoulos N, Muanza T. Radiation-induced oral mucositis. Front Oncol. 2017;7:89. doi: 10.3389/fonc.2017.00089.
  5. Gandhi K, Datta G, Ahuja S, Saxena T, Datta AG. Prevalence of oral complications occurring in a population of pediatric cancer patients receiving chemotherapy. Int J Clin Pediatr Dentr. 2017;10:166-71. doi: 10.5005/jp-journals-10005-1428
  6. Cinausero M, Aprile G, Ermacora P, et al. New Frontiers in the Pathophysiology and Treatment of Cancer Regimen-Related Mucosal Injury. Front Pharmacol. 2017;8:1-16. doi: 10.3389/phar.2017.00354
  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. Franco P, Martini S, Di Muzio J, et al. Prospective assessment of oral mucositis and its impact on quality of life and patient-reported outcomes during radiotherapy for head and neck cancer. Med Oncol. 2017;34:81. doi: 10.1007/s12032-017-0950-1
  9. Kim JW, Cha Y, Kim SJ, et al. Association of oral mucositis with quality of life and symptom clusters in patients with solid tumors receiving chemotherapy. Support Care Cancer. 2012;20:395-403. doi: 10.1007/s00520-011-1126-8.
  10. Barkokebas A, Silva IH, de Andrade SC, et al. Impact of oral mucositis on oral-health-related quality of life of patients diagnosed with cancer. J Oral Pathol Med. 2015;44:746-51. doi: 10.1111/jop.12282
  11. Chen HM. Patients’ experiences and perceptions of chemotherapy-induced oral mucositis in a day unit. Cancer Nurs. 2008;31:363-9. doi: 10.1097/01.NCC.0000305762.89109.29
  12. Bensinger W, Shubert M, Ang KK, et al. NCCN task force report: prevention and management of mucositis in cancer care. JNCCN. 2008;6(suppl 1):S1-S21.
  13. Sroussi HY, Epstein JB, Bensadoun R-J, et al. Common oral complications of head and neck cancer radiation therapy: mucositis, infections, saliva change, fibrosis, sensory dysfunctions, dental caries, periodontal disease, and osteoradionecrosis. Cancer Med. 2017;6:2918-31. doi: 10.1002/cam4.1221
  14. Kepivance (palifermin). [Prescribing information]. Stockholm, Sweden: Swedish Orphan Biovitrum AB; 2011.
  15. Spielberger R, Stiff P, Bensinger W, et al. Palifermin for oral mucositis after intensive therapy for hematologic cancers.  N Engl J Med. 2004;351:2590-8.
  16. Peng H, Chen B-B, Chen L, et al. A network meta-analysis in comparing prophylactic treatments of radiotherapy-induced oral mucositis for patients with head and neck cancers receiving radiotherapy. Oral Oncol. 2017;75:89-94. doi: 10.1016/j.oraloncology.2017.11.001
  17. Soligenix. Soligenix Receives FDA Protocol Clearance of Pivotal Phase 3 Clinical Trial of SGX942 for the Treatment of Oral Mucositis in Head and Neck Cancer Patients. 2017. Press Release. https://www.soligenix.com/news/soligenix-receives-fda-protocol-clearance-pivotal-phase-3-clinical-trial-sgx942-treatment-oral-mucositis-head-neck-cancer-patients/. Accessed February 15, 2018.
  18. 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. doi: 10.1007/s00520-013-1871-y

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General Oncology Side-Effect Management