D’Hondt et al alkaline phosphatase levels (required for dephosphorylation of amifostine into its active metabolite WR-1065), and higher pH of normal tissues (Spencer et al 2005). One randomized trial has shown that amifostine reduced the incidence of xerostomia, but not the severity of oral mucositis after radiotherapy for head-and-neck cancers (Brizel et al 2000). A recent randomized trial suggested that for ovarian cancer patients, the frequency of severe grade III to IV carboplatin- and paclitaxel-induced mucositis was reduced with amifostine infusion (Lorusso et al 2003). The study by Spencer and colleagues (2005) also suggested that amifostine reduced the median grade of oral mucositis and the severity of mucositis, but not the requirement of parenteral nutrition or analgesic use after high-dose melphalan and HSCT for multiple myeloma. Finally, amifostine reduced the frequency of severe esophagitis after chemo-radiotherapy for non-small-cell lung cancer (NSCLC) (Komaki et al 2002). Guidelines do not recommend amifostine for prevention of oral mucositis except for NSCLC patients undergoing concomitant chemo-radiotherapy (Rubenstein et al 2004). One of the main issues with amifostine administration is the toxicity. Nausea, vomiting, hypotension, sneezing, flushing, somnolence, metallic taste, allergic reactions, and hypocalcemia have been frequently reported. However, subcutaneous injection could be more tolerable (Bardet et al 2002). Chlorhexidine Chlorhexidine reduces mucosal colonization by microorganisms, but this effect has never been translated into clinical benefits for patients receiving either chemotherapy or conventional or high-dose radiotherapy (Saadeh 2005). In a randomized trial, chlorhexidine was found to be less effective and more toxic than a placebo rinse in patients with head-and- neck tumors receiving radiotherapy (Foote et al 1994). Chlorhexidine is not recommended in the clinical guidelines (Rubenstein et al 2004). In addition, chlorhexidine has several side effects including inflammation, mouth discomfort, taste alterations, and teeth staining (Pitten et al 2003). Gelclair® Gelclair® was approved by the FDA in 2002 as a class 1 medical device. It is a bioadherent gel that works by forming a coating over mucosal lesions. Gelclair consists of polyvinylpyrrolidone, hyaluronic acid, and glycerrhetinic acid. It is thought that this molecule has anti-inflammatory properties. This preparation is well tolerated and easy to use and has been shown to be 164 effective in reducing pain and oral discomfort in patients with mucositis (Innocenti et al 2002). Benzydamine Benzydamine is a non-steroidal anti-inflammatory drug used topically. It also has cytoprotective, anesthetic, and antimicrobial properties (Wright et al 2005). This drug is recommended by the MASCC/ISOO panel of experts for prevention of radiotherapy-induced mucositis (Rubenstein et al 2004). This product is safe, but its efficacy for prevention of chemotherapy-induced mucositis is still unknown (Peterson et al 2004). Glutamine Glutamine is a neutral amino acid rich in nitrogen that plays an important role in mucosal cellular metabolism. In cancer patients treated by chemotherapy or radiotherapy, a significant glutamine depletion is frequently observed (Saadeh 2005). Conflicting results have been published about the effect of glutamine repletion in cancer patients. No positive effect was reported for patients receiving 5-FU chemotherapy (Jebb et al 1994; Okuno et al 1999); however, two smaller studies demonstrated a reduction in oral mucositis grade and duration for patients who did not receive 5-FU (Skubitz and Anderson 1996; Anderson, Schroeder, et al 1998). The effect of glutamine repletion in the BMT setting is also controversial with positive (Anderson, Ramsay, et al 1998) and negative (Pytlik et al 2002) studies. AES-14 (SaforisTM) AES-14 (SaforisTM) by Aesgen Inc., Princeton, NJ, USA, is an oral suspension delivering concentrated L-glutamine to the oral mucosa through a proprietary vehicle. This system received a fast-track approval from the FDA in January 2003 based on studies showing a reduction of mucositis severity in BMT patients and a shorter healing time after radiation (Elting et al 2004) compared with placebo. In addition AES-14 has a very favorable toxicity profile. Hematopoietic-growth factors It has long been observed that mucositis often resolves within days of granulocyte recovery. Some reports suggest that granulocyte colony-stimulating factor (G-CSF) or granulocyte- macrophage colony-stimulating factor (GM-CSF) can reduce oral mucositis by accelerating neutrophil recovery (Wilkes 1998). However, randomized trials are controversial with positive (Chi et al 1995; Kannan et al 1997) and negative results Therapeutics and Clinical Risk Management 2006:2(2)