D’Hondt et al Epidemiology Cancer patients consider oral mucositis to be the most difficult treatment-related toxicity to endure. The frequency of oral mucositis is about 30% to 40% in the general cancer patient population (Sonis 2004). However, patients receiving high- dose chemotherapy (HDC) conditioning before hematopoietic stem cell transplant (HSCT) have a 76% chance of developing mucositis (Rao Naidu et al 2004). In addition, patients receiving radiation, especially for head-and-neck cancers, have a 30% to 60% chance of suffering from this complication. The increased incidence is not only related to drugs used but also to the number of chemotherapy cycles and the previous occurrence of mucositis (Rao Naidu et al 2004). It is estimated that annually there are approximately 400 000 cases of therapy- induced oral mucositis (Rao Naidu et al 2004). Risk factors can be divided into two main categories: risks related to patient status and those related to the treatment itself. Patient-related risks Age has been shown to be a risk factor because children experience more frequent and debilitating mucositis, probably because of high cellular turnover. In addition, patients over 50 years of age may develop severe mucositis, perhaps because of insufficient DNA repair (Balducci and Exterrman 2000). Female patients are more likely to develop oral mucositis, for instance after 5-fluorouracil (5-FU) treatment (Sonis 1998). Nutritional status, type of malignancy, drug-induced xerostomia (dry mouth), pre-existing mouth damage, and periodontal status also play a role. Tobacco and alcohol consumption is probably an important risk factor, although this remains controversial (Dood et al 1999). In addition, there has been a recent focus on genetic predisposition for oral mucositis. Enzymatic phenotypes probably play a key role in explaining the huge variation of interindividual tolerance to anticancer treatment. For instance, Ulrich et al (2001) reported that in patients undergoing HDC for HSCT, a polymorphism in the 5, 10-methyl- enetetrahydrofolate reductase gene was associated with a differential rate of oral mucositis after treatment with methotrexate. Finally, previous episodes of oral mucositis are also an important risk factor. Treatment-related risk Mucositis is the second most frequent dose-limiting factor in patients receiving chemotherapy (Peterson and Cariello 2004). Chemotherapeutic drugs affecting DNA synthesis are particularly stomatotoxic. For instance, 5-FU administration is associated with oral mucositis in about 40% of patients 160 (Popescu et al 1999), and grade 3 to 4 oral mucositis is observed in 10% to 15% of 5-FU recipients (MAC 1998). There is an increased risk of mucositis with bolus and continuous infusions compared with prolonged and repetitive low doses of chemotherapeutic agents (Rao Naidu et al 2004). Other cytotoxic agents are known to be very damaging to mucosa (eg, alkylating agents such as anthracyclines and taxanes and folate-based drugs such as methotrexate) (Sharma et al 2005; Wright et al 2005). Finally, some drugs are excreted in the saliva, such as methotrexate and etoposide (Rao Naidu et al 2004). The dose of chemotherapy is also of great importance, as illustrated by the 85%–95% incidence of mucositis in HSCT recipients. Conditioning regimens including melphalan are associated with high rates of oral mucositis (Wardley et al 2000). In this setting, mucositis has been reported by patients as the most distressing side effect they had to cope with (Bellm et al 2000). It is interesting to note that allogeneic transplant recipients experience higher grades of mucositis compared with those receiving autologous transplants (Wright et al 2005). In addition, there is a strong relationship between low neutrophilic count and the severity of stomatitis (Saadeh 2005). Radiotherapy is also associated with an increased risk of mucositis. The risk varies with dose, fractioning, and the site of radiotherapy. In head-and-neck cancer patients, the incidence of mucositis is over 50%, and this rate increases when chemotherapy is given concomitantly or in HSCT recipients when total body irradiation is administered (Trotti et al 2000; Rubenstein et al 2004). Accelerated fraction even increases the risk of mucositis to >70%, at which point mucositis is often dose limiting (Trotti et al 2000). A summary of the different risk factors is presented in Table 1. The severity of mucositis has a direct influence on the treatment planning with the necessity of dose reductions, delays, or even discontinuations of anticancer therapy. This condition also can favor the development of life-threatening infections, especially if the patient is neutropenic. We recently reported the case of a head-and-neck cancer patient with extensive stomatitis who developed a Saccharomyces cerevisiae fungemia infection during concomitant chemoradiotherapy (Henry et al 2004). Oral mucositis has important economic costs. In a recent economic study, patients with mucositis had significantly higher costs for nutrition/hydration support and prescription medications but not for hospitalization compared with head- and-neck cancer patients free of mucositis. This difference resulted, however, in higher total costs for patients with mucositis (Peterman et al 2001). Therapeutics and Clinical Risk Management 2006:2(2)