Oral Mucositis Complicating Chemotherapy and/or Radiotherapy: Options for Prevention and Treatment

Abstract

The incidence and severity of oral mucositis is influenced by the type of antineoplastic treatment administered and by patient-related factors. Severe courses of oral mucositis are observed during simultaneous radiochemotherapy, which Oral Mucositis Complicating Chemotherapy and/or Radiotherapy: Options for Prevention and TreatmentWolfgang J. Köstler, MD; Michael Hejna, MD; Catharina Wenzel, MD; and Christoph C. Zielinski, MD 290 CA A Cancer Journal for Clinicians ABSTRACT Chemotherapy-and radiotherapy-induced oral mucositis represents a therapeutic challenge frequently encountered in cancer patients. This side effect causes significant morbidity and may delay the treatment plan, as well as increase therapeutic expenses.The pathogenesis of this debilitating side effect can be attributed to the direct mucosal toxicity of cytotoxic agents and ionizing radiation and to indirect mucosal damage caused by a concomitant inflammatory reaction exacerbated in the presence of neutropenia, and the emergence of bacterial, mycotic, and viral infections. affects virtually all patients with head and neck cancer who receive this therapeutic modality. 8 However, up to 40% of patients treated with conventional chemotherapy and the more than 70% of patients undergoing conditioning therapy for bone marrow transplantation also experience oral treatment-related complications. 9,10The pathogenesis of oral mucositis is not fully understood, yet it is thought to involve direct and indirect mechanisms. Direct mucosal injury by radiation and chemotherapy interfere with the average 5-to 14-day turnover time of the oral epithelium 11 and induce apoptosis. Indirect stomatotoxic effects that result from the release of inflammatory mediators, loss of protective salivary constituents, and therapyinduced neutropenia have been postulated to contribute to the development of oral mucositis and also promote the emergence of bacteria, fungi, and viruses on damaged mucosa.12 Although a linear relationship among the occurrence of oral mucositis, oral and systemic granulocyte counts, and a coincidence of resolution of mucositis with neutrophil recovery, has been demonstrated, 10,[13][14][15] significant mucositis can occur in the absence of myelotoxicity. 16,17 In addition, the prophylactic or therapeutic elimination of the pathogenic mucosal flora frequently observed in patients developing oral mucositis by various antiseptic and antimicrobial agents can at most alleviate the course of oral mucositis (see Antimicrobal Agents p. 302).Based upon these considerations, newer pathophysiologic concepts have emerged characterizing oral mucositis as having an initial inflammatory/vascular phase, an epithelial phase, a (pseudomembraneous) ulcerative/bacteriological phase and a healing phase.18 During the inflammatory phase, tissue injury induces release of free radicals, modified proteins and proinflammatory cytokines including interleukin-1β, prostaglandins and tumor necrosis factor-α (TNF-α) by epithelial, endothelial, and connective tissue cells. These ...

Adipose mesenchymal stromal cells minimize and repair radiation-induced oral mucositis

“…Grade 3 signifies the presence of ulceration, extensive erythema, and inability to swallow hard food [4]. As .…”

“…Many therapies and procedures have been tried for RIOM locally and systematically, e.g. local anesthesia, analgesics, antiinflammatory drugs, oral care, midline radiation blocks, benzydamine, oral cryotherapy using ice, exposure to soft Laser, and systemic administration of keratinocyte growth factor (palifermin) [3,4,9]. Local application of honey appears to be a very promising RIOM local therapy as well [10][11][12][13].…”

“…Although pharmacological and non-pharmacological therapies were applied for RIOM, yet, no single therapy was identified to significantly minimize and/or repair RIOM. Such expected significant therapeutic benefit would be mediated through reducing the injury severity and duration to a clinically relevant extent [2,4,5,12,. The inflammatory nature of the RIOM directs the current studies towards finding a convenient antiinflammatory therapy for such tissue injury.…”

“…The recent studies proposed that the pathogenesis of RIOM is composed of 4 phases. An initial inflammatory/vascular phase, an epithelial phase, a (pseudomembraneous) ulcerative/bacteriological phase, and a healing phase [4,6].…”

N-acetyl cysteine for prevention of oral mucositis in hematopoietic SCT: a double-blind, randomized, placebo-controlled trial

“…27 Among different agents that have been used to prevent OM, keratinocyte growth factor (palifermin) and cryotherapy have shown some advantages. Sucralfate has also been shown to be effective in reducing the severity of mucositis but other interventions such as aloe vera, amifostine, intravenous glutamine, G-CSF, honey, laser and antibiotic lozenges containing polymixin/ tobramycin/amphotericin (PTA) have shown weaker evidence of benefit.…”