Oral mucositis is a painful inflammation and ulceration of mucous membranes of the oral cavity.  It is a common side effect of most chemotherapeutic drugs, and radiotherapy of the oral, and head and neck cancers.1,2  In addition to impacting the quality of life of cancer patients, it influences treatment decisions, often requiring reductions of dose and delays or even discontinuation of therapy resulting in tumor rebound and cancer relapse. Mucositis-related ulcers are also prone to infections, which may be life-threatening and may exacerbate underlying oral, gum, dental, and periodontal problems.3 Oral mucositis is a debilitating complication commonly seen in 25% to 33% of cancer patients treated with chemotherapy2; and nearly 100% in those treated with high-dose myeloablative chemotherapy before undergoing bone marrow transplantation (BMT).2,4 

Mucositis management also imposes additional economic burden on cancer patients, including palliative drugs and indirect costs related to pain management and nutrition, or hydration support. In one study, economic impact on treating oral mucositis was an additional $1,700 to $6,000 per patient, with additional hospital costs as high as $25,000 per patient.5 In 2009, Medicare reimbursed over $40,000 per patient with ulcerative mucositis lesions.6 

Although oral mucositis is an unmet medical need, it has received little attention by the pharmaceutical companies.

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Risk factors
The risk factors for oral mucositis are broadly divided into 2 categories: those influenced by patient status, and those related to the cancer-treatment regimen. Patient status includes age, gender, lifestyle, and genetic disposition. Children are at high risk due to rapid cell proliferation and turnover, as are people over 50 years of age, due to compromised DNA repair potential. Women have a higher incidence compared to men; the reasons for which are not clear. Poor nutritional status, smoking, alcohol use, and periodontal disease are other patient-related risk factors.7 A polymorphism in the 5,10 methylene-tetrahydrofolate reductase (MTHFR) gene C677T is a known genetic risk factor that can cause methotrexate toxicity and result in an increase in the severity of oral mucositis in patients treated with the drug. Approximately 10% to 12% of the population carries this genotype.8

A broad variety of chemotherapeutic drugs exhibit oral mucositis as a side effect. High-risk drugs include 5-fluorouracil (5-FU), cyclophosphamide, doxorubicin, methotrexate, anthracyclines and taxanes.9,10 In general, the risk is higher with bolus administration than continuous infusion for the same dose. Patients taking drugs which target DNA synthesis, such as 5-FU, are particularly susceptible to oral mucositis with symptoms in 40% of patients and 10% to 15% of patients with grade 3 or 4 oral mucositis.7