saliva in the pathogenesis of oral injury is unclear. Saliva plays a major role in oral homeostasis, notably through salivary immunoglobulin A (Epstein et al 2002); however, surprisingly, an attempt to increase production by pilocarpine hydrochloride in cases of decreased or absent saliva (ie, xerostomia) failed to moderate oral mucositis (Lockhart et al 2005). Prevention and treatment of oral mucositis Many strategies exist to prevent and treat oral mucositis; most of these are not generally accepted and are frequently based on anecdotal reports or experiences. The lack of large, well- designed randomized clinical studies adds to the confusion. Recently a panel of experts reviewed the oral mucositis literature and summarized the conclusions in clinical guidelines (Rubenstein et al 2004; Sonis et al 2004). Fortunately, because of a growing interest in this important side effect of cancer treatment, interesting clinical studies have been reported, and new drugs have been developed and tested. Management of oral mucositis can be artificially divided in three basic components: general oral care, prevention, and palliative cares (Saadeh 2005). General oral care General oral care is the basis of oral mucositis management, and it has a crucial role in prevention of its occurrence. The aim is to reduce some host-related risk factors for stomatitis, including lowering the impact of oral microbial flora. First a pre-treatment oral assessment of the patient should be performed. Comprehensive patient education plays a central role, and a standard oral care protocol should be applied, but there is not enough evidence to recommend one protocol over another (Saadeh 2005). However, collective studies suggest that the use of a systematic protocol improves patient outcome (Rubenstein et al 2004). Some simple care should be suggested, for instance: brushing teeth twice daily using a new toothbrush at each chemotherapy cycle, daily flossing, and mouth rinsing with sterile water after each brushing or flossing. In addition, spicy food, alcoholic beverages, and alcohol-based mouthwashes should be avoided (Larson et al 1998). Topical antimicrobial treatments have frequently been shown to be ineffective in modifying mucositis (Sonis 2004). For instance use of amphotericin B, tobramycin, and polymyxin B has shown efficacy in preventing oral mucositis induced by radiotherapy but not by chemotherapy (Donnelly et al 2003). This paradox can be explained in part by the physiopathology of oral mucositis. These three compounds, in addition to their Therapeutics and Clinical Risk Management 2006:2(2) Oral mucositis and its treatments anti-infective activity, also affect the production of pro- inflammatory cytokines. Amphotericin B induces the expression of genes coding for TNF-α and IL-1β (Rogers et al 1998) while both tobramycin and polymyxin B attenuate the production and activity of these cytokines (Frieling et al 1997). Prevention Prevention is the second most important factor in addressing oral mucositis. Cryotherapy Cryotherapy consists of the use of ice chips when bolus 5-FU chemotherapy is administered. This cryotherapy induces a temporary vasoconstriction, reducing blood flow and chemotherapy delivery to oral mucosa (Saadeh 2005). This procedure has been validated in two randomized clinical trials (Maahood et al 1991; Cascinu et al 1994). The group receiving cryotherapy experienced a reduction in mucositis of approximately 50% (Maahood et al 1991). In practice, ice chips are given for 30 minutes, starting 5 minutes before the beginning of the chemotherapy. It should be noted that this procedure is neither useful for continuous infusion of 5-FU nor for methotrexate and anthracycline-containing therapies since the half-life of these drugs is too long (Rubenstein et al 2004). The advantages of this procedure are its simplicity, lack of toxicity, and low cost. Low level laser therapy Low level laser therapy (LLLT) is also an important part of the prevention strategies of mouth mucositis (Genot and Klastersky 2005). This procedure has been shown to be effective in patients receiving HDC and HSCT (Barasch et al 1995; Cowen et al 1997). It promotes wound healing and reduces pain and inflammation (Rubenstein et al 2004). In addition, LLLT produces no toxicity and is nontraumatic to patients but requires expensive materials and is time consuming. Amifostine Amifostine is a radioprotectant pro-drug that when dephosphorylated protects normal but not malignant cells against oxygen-based radicals, alkylator or organoplatinum anticancer drugs (Spencer et al 2005), and radiotherapy. It acts as a free-radical scavenger and has been shown to reduce pro- inflammatory cytokine levels (Sonis 2004). The protection of normal cells results in part from improved vascularity, higher 163