5537 Background: We reported inferior outcomes for LAHNSCC patients (pts) that received concurrent C225 vs. high-dose CDDP with IMRT (IJROBP 2011; 81:915). Prior to FDA approval of C225 for LAHNSCC, non-CDDP candidates at our institution were treated with 5FU/CBDCA (JNCI 1999; 91:2081). The purpose of this study was to compare the outcomes of concurrent C225 vs. 5FU/CBDCA vs. CDDP with IMRT for LAHNSCC. Methods: Retrospective review of records was performed for pts treated at MSKCC with concurrent C225 (n=49) vs. 5FU/CBDCA (n=52) vs. high-dose CDDP (n=259) and IMRT from 11/02 to 04/08. Overall survival (OS), locoregional failure-free survival (LRFS), and late toxicity for all pts and oropharyngeal subset were obtained. Outcomes were analyzed using univariate/multivariate Cox proportional hazards model or competing-risks analysis. Multivariate OS analysis was confirmed by propensity score adjustment. Results: Pts were similar with regard to site, overall stage, and alcohol/tobacco history. Compared to pts treated with CDDP, those who received C225 or 5FU/CBDCA were older, with lower performance status, higher Charlson score, higher T stage, and worse renal function. With median follow-up of 53.1 months for survivors, the 4-year OS was 40.9% (95% CI 26.0-55.2%) for C225 vs. 70.2% (95% CI 55.5-80.9%) for 5FU/CBDCA vs. 86.9% (95% CI 82.0-90.6%) for CDDP. Compared with CDDP, C225 (hazard ratio [HR] 4.01, p