Purpose The purpose of this study was to estimate the risk and severity of oral and gastrointestinal mucosal toxicities associated with selected targeted agents. Methods We searched the English-language literature in February 2011 for reports of randomized clinical trials comparing a FDA-approved targeted agent to a standard of care regimens. Long-term follow-up and secondary reports of trials were excluded, leaving 85 studies for analysis. Using metaanalytic methods, we calculated the relative risks of oral and gastrointestinal toxicities, adjusting for sample size using the inverse variance technique. For each targeted agent and each side effect, we calculated the number needed to harm, the number of patients that, if treated with the more toxic regimen, would produce one additional episode of the toxicity. Results Oral mucositis was significantly more frequent among patients treated with bevacizumab, erlotinib, sorafenib, or sunitinib, although this difference was confined to low-grade mucositis. The clinical significance of these findings is unclear given its low incidence and mild severity. In contrast, diarrhea was significantly more frequent with most of the targeted agents studied, with adjusted relative risks between 1.5 and 4.5. An additional patient with diarrhea will be observed for every three to five patients treated with these targeted agents, compared with conventional regimens. Conclusions Oral mucosal toxicities occasionally complicate treatment with these targeted agents, but the clinical significance of this finding is not clear. Diarrhea is a hallmark of treatment with these targeted agents; this side effect should be carefully ascertained to permit early intervention and control.

e20509 Background: Pathways associated with proinflammatory molecules are upregulated in oral mucositis. Lalla (Support Care Cancer 18:95, 2010) found an association between mucositis pain scores, tissue COX-1, and salivary prostaglandins in 4 patients receiving dose-dense chemotherapy. We investigated whether similar changes would be seen with radiotherapy (XRT)-induced mucositis. Methods: Patients receiving XRT including the oropharynx were evaluated at 4 time points, before XRT, midway through XRT, end of XRT, and 1 month after XRT. Subjective report of pain and objective mucositis scores were recorded. Patients also provided a 5-minute stimulated saliva specimen at each time point collected on ice with a protease inhibitor cocktail. Proteins were estimated using a Bradford assay. Prostaglandins were measured using ELISA assays. Results: 8 evaluable patients entered the study, including 7 male/1 female, median age 60 (range 48-66), primary site (oropharynx 1, unknown primary 1, base of tongue 3, tonsil 1, tongue 1, supraglottis 1), median XRT 7000 rads (range 6000-7200 rads), concomitant chemotherapy (cisplatin 7, none 1), histology (squamous 7, mucoepidermoid 1). Pain and mucositis scores increased during XRT and improved at 1 month after XRT. No increase in COX-2 levels was seen. Salivary PGD2, PGE2, and PGF2 increased from baseline with the greatest increase 1 month after XRT. There was a significant time effect for PGF2 (p=0.028) and marginal time effects for PGD2 (p=0.107) and PGE2 (p=0.069). Conclusions: Increased salivary prostaglandins are seen during and after XRT-induced oral mucositis, suggesting a role for proinflammatory mediators and providing a possible therapeutic target. Clinical trial information: NCT01252498. [Table: see text]

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