6020 Background: The combination of radiotherapy (RT) and cetuximab (CTX) represents a new treatment option for patients with locally advanced head and neck cancer (LASCCHNC) (Bonner et al. NEJM 2006). However recent case reports have raised concern about unexpectedly high toxicity rates with such an approach. We report herein a single institution experience using RT and CTX for LASCCHNC. Methods: Acute toxicity was prospectively recorded (CTC v3.0) in 48 patients treated with RT and CTX, in line with the Bonner regimen, between March 2006 and June 2007. Thirty-four received a daily fractionated schedule (RT/CTX, 66–70Gy/33–35#/7 weeks) and 14 received a concomitant boost (CB-RT/CTX, 70Gy/40#/6 weeks). A matched group who received cisplatin with daily-fractionated radiotherapy was also analyzed (RT/CDDP). Results: The main clinical characteristics were comparable between the 3 patient groups and the Bonner trial (table). RT/CTX resulted in more grade ≥3 radiation-induced toxicities than RT/CDDP (skin p=0.007; p=0.008) and when compared to the Bonner study (skin p<0.0001; oral p=0.026). The addition of a concomitant boost further increased the toxicity rates. No grade 4 or 5 toxicity was reported. The rate of CTX-specific skin rash was comparable to the Bonner trial. RT/CDDP led to reduced overall treatment compliance (59% vs 79%, p=0.003) and more septic episodes (12% vs 4%, p=0.04). Conclusions: This community-based experience using CTX and RT for LASCCHNC revealed higher acute radiation-induced skin and oral toxicity rates than reported in the Bonner trial. However these toxicities were manageable and did not lead to a reduction in treatment compliance. Patient and Treatment Characteristics SLH RT/CDDP (n=34) SLH RT/CTX (n=34) SLHCB-RT/CTX (n=14) Bonner Trial1 (n=211) Age (yrs): Median (range) 58 (29–79) 63 (44–82) 61 (39–76) 56 (34–81) WHO PS: 0–1/2 (%) 97/3 94/4 93/7 90/10 Site : Oroph./Hypoph-Larynx (%) 47/53 59/41 50/50 56/44 AJCC Stage III/IV (%) 44/56 35/65 43/57 26/74 RT Dose 66–70Gy 66–70Gy 70Gy 70–72Gy ≥G3 skin toxicity (%) 18 58 86 23 ≥G3 oral toxicity (%) 44 78 77 56 ≥G3 acneiform rash (%) 0 11 4 17 Compliance With Treatment (%)(<5 days delay & >4 infusions) 59 79 86 NA PS: performance status, oroph.: oropharynx, hypoph.: hypopharynx No significant financial relationships to disclose.