Hypofractionated Versus Conventionally Fractionated Radiotherapy for Initial Distant Metastases Nasopharyngeal Carcinoma

PRIMARY OBJECTIVES:

I. To determine if hypofractionated with a smaller total dose radiation is not inferior to standard-dose radiation in progression-free survival for initial distant metastases nasopharyngeal carcinoma .

SECONDARY OBJECTIVES:

I. To evaluate if hypofractionated with a low total dose radiation is not inferior to standard-dose radiation in overall survival and locoregional failure-free survival for initial distant metastases nasopharyngeal carcinoma II. To evaluate if hypofractionated with a low total dose radiation with chemotherapy decrease treatment-related toxicities

OUTLINE:

Patients are randomized to one of the two treatment arms

ARM 1: Patients receive hypofractionated with a low total dose radiation with induced chemotherapy and adjuvant chemotherapy.Hypofractionated dose IMRT: GTVnx 60Gy, GTVnd 60Gy, PTV1 50Gy and PTV2 45Gy in 25 fractions, 5 days/week.

Induced chemotherapy: Paclitaxel 135mg/m2 D1+Cisplatin 75mg/m2 D1(or D1-3), 3-week chemotherapy for 3 cycles. After radiation, patients receive adjuvant chemotherapy Paclitaxel 135mg/m2 D1+Cisplatin 75mg/m2 D1(or D1-3), 3-week chemotherapy for 3 cycles.

ARM 2: Patients receive standard-dose radiation with concurrent chemotherapy. Standard-dose IMRT: GTVnx 69.69Gy, GTVnd 60-68Gy, PTV1 59.4Gy and PTV2 54Gy in 33 fractions, 5 days/week.

Induced chemotherapy: Paclitaxel 135mg/m2 D1+Cisplatin 75mg/m2 D1(or D1-3), 3-week chemotherapy for 3 cycles. After radiation, patients receive adjuvant chemotherapy Paclitaxel 135mg/m2 D1+Cisplatin 75mg/m2 D1(or D1-3), 3-week chemotherapy for 3 cycles.

After completion of study therapy, patients are followed up every 3-4 months for 2 years, then every 6 months for 3 years.

Inclusion criteria

• Patients with newly histologically confirmed non-keratinizing (according to WHO histologically type) Tumor staged as any T or any N with M (according to the 8th AJCC edition).
• No pregnant female
• Age between 18-70
• Normal complete blood count level (hemoglobin >10 g/dL, white blood cells ≥4000/μL, platelets ≥100 000/μL)
• Normal hepatic functions (serum total bilirubin ≤1.6 mg/dL, serum transminase < 2.5 times higher than upper limit)
• Normal renal function (serum creatinine ≤1.5 mg/dL, creatinine clearance ≥60 mL/min)
• Karnofsky performance status (KPS) score of at least 70
• Without radiotherapy or chemotherapy
• Patients must give signed informed consent

Exclusion criteria

• Other or mixed pathological type
• age > 70 years or <18 years
• Prior chemotherapy, radiation, surgical resection or target therapy of the primary tumor;
• Significant medical or psychiatric illnesses that in the physician's judgment (uncontrolled coronary heart disease, cardiomyopathy and/or heart failure requiring hospitalization. Uncontrolled hypertension or history of myocardial infarction within one year. Uncontrolled diabetes mellitus. Acute bacterial or fungal infection requiring intravenous antibiotics;
• Refused to sign informed consent form
• Concurrent pregnancy or lactation
• History of a second malignancy other than nasopharyngeal carcinoma