Table 2. Oral Complications of Cancer Chemotherapy continued...
Ulcerative oral mucositis occurs in approximately 40% of patients receiving chemotherapy. In approximately 50% of these patients, the lesions are severe and require medical intervention including modification of their cytotoxic cancer therapy. Normal oral mucosal epithelium is estimated to undergo complete replacement every 9 to 16 days. Intensive chemotherapy can cause ulcerative mucositis that initially emerges approximately 2 weeks after initiation of high-dose chemotherapy.[2,3,4]
Chemotherapy directly impairs replication of basal epithelial cells; other factors, including proinflammatory cytokines and metabolic products of bacteria, may also play a role. The labial mucosa, buccal mucosa, tongue, floor of mouth, and soft palate are more severely affected by chemotherapy than are the attached, heavily keratinized tissues such as the hard palate and gingiva; this may be caused by relative rate of epithelial cell turnover among high-risk versus low-risk oral mucosal tissues. Topical cryotherapy may ameliorate mucositis caused by agents such as 5-fluorouracil (5-FU) by reducing vascular delivery of these toxic agents to replicating oral epithelium.
It is difficult to predict whether a patient will develop mucositis strictly on the basis of the classes of drugs that are administered. Several drugs are associated with a propensity to damage oral mucosa:
- The platinum coordination complexes, including cisplatin and carboplatin.
- Mammalian target of rapamycin (mTOR) inhibitors (a new class of targeted cancer therapeutic agents).[6,7]
Anecdotal evidence suggests that patients who experience mucositis with a specific chemotherapy regimen during the first cycle will typically develop comparable mucositis during subsequent courses of that regimen.
Other oral complications typically include infections of the mucosa, dentition/periapices, and periodontium. Prevalence of these infections has been substantiated in multiple studies.[8,9,10,11] Specific criteria for determining risk of infectious flare during myelosuppression have not been developed. Guidelines for assessment primarily address both degree of severity of the chronic lesion and whether acute symptoms have recently (i.e., <90 days) developed. However, chronic asymptomatic periodontitis may also represent a focus for systemic infectious complications since bacteria, bacterial cell wall substances, and inflammatory cytokines may translocate into the circulation via ulcerated pocket epithelium. In addition, poor oral hygiene and periodontitis seem to increase the prevalence of pulmonary infections in high-risk patients.
Resolution of oral toxicity, including mucositis and infection, generally coincides with granulocyte recovery. This relationship may be temporally but not causally related. For example, oral mucosal healing in hematopoietic stem cell transplantation patients is only partially dependent on rate of engraftment, especially neutrophils.
Head/Neck Radiation–induced Complications
Head and neck radiation can cause a wide spectrum of oral complications (refer to the list of Oral Complications of Radiation Therapy below). Ulcerative oral mucositis is a virtually universal toxicity resulting from this treatment; there are clinically significant similarities as well as differences compared with oral mucositis caused by chemotherapy. In addition, oral mucosal toxicity can be increased by use of head and neck radiation together with concurrent chemotherapy.