Rationale of induction chemotherapy:~Distant metastasis is the major cause of treatment failure and deaths in patients with loco-regionally advanced NPC.~Concurrent chemoradiotherapy may prolong survivals for patients with advanced NPC, but it is still flawed by high incidence of distant metastasis.~Induction chemotherapy with MEPFL has been shown to reduce the incidence of distant metastasis in a Phase II study.~Induction chemotherapy plus concurrent chemoradiotherapy may improve the survival of patients with advanced NPC.~Objectives:~Investigate the effect of induction MEPFL chemotherapy followed by concurrent chemoradiotherapy (CCRT) on the disease control and survival in treatment of patients with advanced NPC.~Study design:~This is a randomized, multi-center Phase III study. Patients will be randomized to CCRT with or without the MEPFL induction chemotherapy.~Type and number of patients:~Patients with stage IVA (T4) and/or IVB (N3) but without distant metastasis will be enrolled. A total of up to 480 patients will be randomized to detect an improvement of median overall survival from 5.8 to 8.7 years, with an a=0.05 and power of 0.8 using a two-sided logrank test with one interim analysis.~Treatment schedule:~Induction chemotherapy and CCRT:~Arm A: Weekly cisplatin concurrently with radiotherapy Arm B: Induction MEPFL three cycles followed with weekly cisplatin concurrently with radiotherapy.~Study endpoints:~The primary endpoint is the disease-free survival that will be calculated as the duration between the date of randomization and the date of recurrence of NPC at any site including persistent disease after +induction chemotherapy/CCRT, or death from any cause (failed), or the date of withdrawal (last contact date, censored), or the scheduled data analysis date (censored).( revised 8/27/2004)
Investigate the effect of induction MEPFL chemotherapy followed by concurrent chemoradiotherapy (CCRT) on the disease control and survival in treatment of patients with advanced NPC.