Recent data (RTOG 90–03 and RTOG 99–14) strongly suggest that concomitant boost radiation (AFX-CB) and concurrent chemoradiation offer a local control advantage in advanced head and neck cancer patients. Based on our previous experience treating unresectable head and neck cancer, we initiated a phase II trial delivering CDDP concurrent with AFX-CB for advanced nasopharyngeal carcinoma (NPC). From 2/99–7/05, 45 patients with newly diagnosed stage IIa-IV NPC were treated with AFX-CB to 70Gy/6 weeks (BID RT last 2 weeks with a 3D-conformal plan, 6 hr interfraction interval) with 2–3 cycles of concurrent CDDP (100mg/m2) on day 1, 22, 43 of radiation followed by adjuvant 5-Fluorouracil/CDDP for 3 cycles. The median age was 46 (24 to 83) and 20 patients were male. Disease characteristics were as follows: 1997 AJCC stage: II-8; III-14 and IV-23, T3/T4 66%, N2/N3 55%. With a median follow-up of 27mo. (3–78 mo.), the crude local control rate (LC) was 93%, regional control (RC) was 98%, locoregional control (LRC) 91%, freedom from distant metastasis (FFDM) was 86%, disease-free survival (DFS) was 82%, and overall survival (OS) was 89%. Eighty-six percent of patients were able to receive 2–3 cycles of adjuvant chemotherapy. Four of the 6 distant metastases occurred 3 years post-treatment. One of the 3 local failures was salvaged with additional chemoradiation and is without evidence of recurrence 23 months later. Thus, the total crude local control is 95%. Among 29 T3/T4 patients, local control was 93%. For all patients, the three year actuarial LC, RC, LRC, FFDM, DFS and OS were 95%, 98%, 93%, 94%, 86% and 87%, respectively. Major grade 3 acute toxicities include mucositis (59%), dysphagia (41%), vomiting (20%) and anemia (4.5%). Average hemoglobin drop was 2.3 gm (17.7%). Ninety percent of patients received erythropoietin support and near 20% required blood transfusion. Late toxicities included grade 3 tinnitus in 1, grade 2 serous otitis in 1, osteoradionecrosis in 1, brain necrosis in 2 and grade 2 xerostomia in 80%. AFX-CB with concurrent and adjuvant chemotherapy for advanced NPC provides excellent locoregional control and acceptable toxicity. Future efforts will focus on decreasing toxicity and increasing systemic control.