Objective:The purpose of this study was to define the maximum tolerated dose (MTD) by describing the dose-limiting toxicity (DLT) of weekly cisplatin concurrently with conventional plus 3-dimensional conformal radiotherapy (CT + 3DCRT) in patients with loco-regionally advanced nasopharyngeal carcinoma (NPC). Methods:Patients with loco-regionally advanced NPC (III/Iva stage) were enrolled into a dose-escalating study. Toxicity was graded according to Common Termi-nology Criteria for Adverse Events version 3.0 (CTCAE v3.0). MTD was defined when 2 of 6 patients developed DLT. The starting dose of cisplatin was 15 mg/m2/w, with a subsequent dose escalation of 5 mg/m2/w in cohorts of 3 new patients. CT + 3DCRT was given to the nasopharynx and the upper neck; the lower neck was treated by a single anterior field irradiation. The prescription dose was 70–80 Gy by 35–40 fractions to the nasopharynx gross tumor, and 66–70 Gy by 33–35 fractions to the positive neck lymph nodes. Results:From Jun. 2008 to Sep. 2009, 24 patients received complete chemoradiotherapy, and all of them were eligible for toxicity evaluation. On the first five dose levels of 15 mg/m2/w and 35 mg/m2/w, no patient experienced DLT. On the next dose level of 40 mg/m2/w, 1 patient experienced DLT of grade 3 myelosuppression for 1.4 weeks, and among the additional 3 patients, no one developed DLT. On the seventh dose level of 45 mg/m2/w, all the patients developed grade 3 myelosuppression for more than 1 weeks, and the dose-escalating trial stopped. The 23 (95.8%) patients achieved clini-cal complete remission (CR) in the local site; 22 (91.7%) achieved CR in the regional site, and all patients got CR 3 months later. After a median follow-up of 16.4 months, 1 patient developed liver metastases 2 months later, 1 patient developed bone metastases 10 months later and 22 kept disease-free survival. Conclusion:The MTD of cisplatin weekly with concurrent CT + 3DCRT for local advanced NPC is 40 mg/m2/w, with myelosuppression as DLT.