The standard treatment for advanced nasopharyngeal carcinoma (NPC) has become external beam radiation therapy (EBXRT) 70 Gy/7 weeks + 3 cycles of concurrent cisplatin followed by 2 to 3 cycles of adjuvant cisplatin/5-fluorouracil (5-FU). Some reports suggest that the addition of low-dose rate brachytherapy to EBXRT also improves local control. To our knowledge, this is the first report of the "triple" combination of EBXRT, brachytherapy, and concurrent/adjuvant chemotherapy. Eleven patients treated from 1992 to 1998 were evaluated. All patients had stage III/IV (excluding T4 lesions) NPC. Treatment consisted of EBXRT (64-70 Gy/7 weeks), followed by a brachytherapy boost (6-15 Gy delivered 0.5 cm deep to the mucosa). Chemotherapy consisted of concurrent cisplatin (100 mg/m2) and post-XRT adjuvant cisplatin (80 mg/m2) and 5-FU (1,000 mg/m2/day x 4 days) for 2 cycles. All 11 patients were evaluable. The average age was 44 years, and median follow-up was 38 months (range: 23-82 months). Median EBXRT dose was 66 Gy, and median brachytherapy dose was 9 Gy (median total dose: 75 Gy). All patients obtained primary tumor complete response (CR). Two patients required post-XRT neck dissection to achieve regional CR. To date, 10 patients are alive with no evidence of disease. The 3-year actuarial survival is 100%. One patient died at 82 months of a late distant recurrence (at 37 months post-XRT). No patient has had a local or neck failure. Chemoradiation plus brachytherapy offers encouraging survival and local-regional control. Further study of this regimen as an alternative or adjunct to intensity-modulated EBXRT is warranted.