5548 Background: We have previously reported the results of Sequential Therapy (ST) with IC followed by weekly D and concurrent daily XRT (Cancer, 2002). In this Phase I/II trial, we investigated concurrent weekly D and the more dose intensive CBR radiation schedule after IC in patients with locally advanced SCCHN. Methods: All patients (AJCC Stage III -7% or IV -93%) were treated with IC (90% 3 cycles; 10% 1 or 2) using cisplatin/5-FU (PF), carboplatinum-F or DPF. Chemoradiotherapy (CRT) consisted of 4 weekly doses of D @ 20 or 25mg/M2 (15 patients/dose level) concurrently with the first 4 weeks of CBR (1.8 Gy qD X 18, 1.8/1.5 Gy bid X 12). Results: 31 patients were enrolled and 30 are evaluable. Median follow up is 21 months, (range of 6–40). Primary sites were: oropharynx 19, oral cavity 2, larynx/hypopharynx 5, unknown primary 4. 87% of patients had N2/N3 disease, 60% had T3/T4 disease. Only 20% of patients had a CR to IC and 50% had a CR to ST (IC, CRT, and Surgery) with 2 PD and 13 PRs. The 2 patients with PD died at 6 and 9 months. A total of 5 patients progressed (2 local, 1 local + distant, 2 distant) and died; another patient died of long-term toxicity. 19 of 26 patients presenting with neck disease had neck dissections. 7 did not; 5 were CRs, 1 had PD and one was inoperable. 7 of 19 (37%) dissections were positive and of these, two are dead of disease. Overall, 24 patients (80%) are alive, NED. No acute DLT was observed at either dose of D, but additional patients were added at 20 mg/M2 because of concerns regarding duration of PEG dependence at 25 mg/M2 and one patient dying late from respiratory arrest associated with severe fibrosis. Conclusions: This intensive ST regimen with concurrent D/CBR as CRT yields good local-regional control and survival in poor prognosis patients. Short term mucositis and late fibrosis are significant but may be justified by long term survival. Study accrual is complete and results of long term toxicity will be presented with additional follow up. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis