In the era of comprehensive therapy, many studies have investigated the value of induction chemotherapy (IC) in the treatment of nasopharyngeal carcinoma (NPC). Concurrent cisplatin and radiotherapy is the foundation of concurrent chemoradiotherapy strategies, and the addition of cisplatin-based induction chemotherapy to concurrent chemoradiotherapy (CCRT) is considered to prolong survival by reducing distant metastasis in patients with high-risk disease. However, the severity of acute toxicities was significantly increased, which can compromise quality of life and lead to interruptions in CCRT. Fortunately, Locoregional control has substantially improved as the intensity-modulated radiation therapy (IMRT) technique has been widely used in the last decades, IMRT improved the treatment outcomes of patients with NPC, especially the local control rate. Currently, in the era of IMRT, whether patients with NPC benefit from IC plus radiotherapy alone and reduce toxicities compared with IC combined with CCRT. Therefore, the investigators propose this randomized phase III prospective study to assess the efficacy and contribution of IC plus radiotherapy alone in locoregionally advanced NPC during IMRT era.

Patients with stage III-IVA (AJCC 8th, included T1-2N2-3 and/or T3-4N0-3 M0) locoregionally-advanced nasopharyngeal carcinoma will be randomized in a 1:1 ratio to experimental arm and active comparator arm. Patients in experimental arm will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 3 cycles before radiation. IMRT is given as 2.0-2.3 Gy per fraction with five daily fractions per week for 6-7 weeks, Cumulative doses were > 66 Gy to the primary tumor and > 50 Gy to the bilateral cervical lymph nodes and potential sites of local infiltration. Patients in active comparator arm will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 3 cycles before radiation. IMRT is given as 2.0-2.3 Gy per fraction with five daily fractions per week for 6-7 weeks, Cumulative doses were > 66 Gy to the primary tumor and > 50 Gy to the bilateral cervical lymph nodes and potential sites of local infiltration. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 3 cycles during IMRT.

Inclusion Criteria:

1. Patients with newly histologically confirmed non-keratinizing (according to WHO histologically type);
2. Tumor staged as III-IVb (according to the 8th AJCC edition);
3. No pregnant female;
4. Age between 18-65;
5. Normal complete blood count level (hemoglobin >10 g/dL, white blood cells ≥4000/μL, platelets ≥100 000/μL);
6. Normal hepatic functions (serum total bilirubin ≤1.6 mg/dL, serum transminase < 2.5 times higher than upper limit);
7. Normal renal function (serum creatinine ≤1.5 mg/dL, creatinine clearance ≥60 mL/min);
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
9. Without radiotherapy or chemotherapy;
10. Patients must give signed informed consent.

Exclusion Criteria:

1. Disease progression in the process of the treatment;
2. The presence of uncontrolled life-threatening illness;
3. History of previous radiotherapy or chemotherapy;
4. Pregnancy or lactation.