Background: In squamous cell carcinoma of head and neck cancer, TPF induction CT improved survival over cisplatin plus fluorouracil (Posner MR: NEJM, vol357, Oct 2007). The main objective of this study is to evaluate the activity and safety of TPF in patients (pts) with locally advanced NPC followed by concomitant cisplatin plus radiotherapy (cCTRT). Methods: Pts with undifferentiated NPC were enrolled from December 2006–December 2012 and received 3 cycles of TPF (docetaxel 75 mg/m2 and cisplatin 75/m2 day 1, plus fluorouracil 750 mg/m2 days 1–5, every 4 wks) with G-CSF days 1–5 post CT. CT was followed by cCTRT with cisplatin 40 mg/m2/wk and radiotherapy (65–70 Gy) starting 4–6 wks after the third cycle of CT. The primary endpoint was overall response rate (ORR) after induction CT and after cCTRT. Secondary end points were safety, disease free survival (DFS), and overall survival (OS). Results: 42 pts have been enrolled (26 M/16 F). UICC 1997 classification: n=9 stage II, n=10 stage III, n=23 stage IV. Median age is 37 yrs (range 18–64). Evocative clinical signs are cervical nodes n=20, rhinologic n=13, otologic n=5, and neurologic n=4. All pts were evaluated for safety and 38 for response.TPF well tolerated with main toxicities grade 3–4 (WHO) were neutropenia 36%, thrombocytopenia 32%, anemia 18%, diarrhea 6%, and mucositis 18%. Four pt died from sepsis that was probably treatment-related. ORR was 90% with an 71.4% (n=27) complete response (CR) rate, 23.6% (n=9) partial response (PR), and 5.2% (n=2) stable disease. No pts progressed after induction CT. Main toxicity during cCTRT was neutropenia grade 3–4 in 9%, mucositis grade 3 in 45% and grade 4 in 4%. Late toxicities were xerostomia grade 3 in 50%. At treatment completion, CR and PR rates were 79% and 20%; 2 pts had stable disease. At a median follow up of 72 months (range 7–72), 8% of pts have shown recurrence or progressive disease. DFS and OS rates at 72 months were 65% and 70%, respectively. Conclusions: TPF followed by cCTRT appears to be an active and feasible regimen with a manageable safety profile and may be a promising therapeutic option for pts with high stage NPC.