Comparison the Effects of Different Neoadjuvant Chemotherapy Regimen on Acute Toxicity, Tumor Response, and Survival in Patients With Advanced Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to investigate the impact of different neoadjuvant chemotherapy schedules of cisplatin and 5-FU on acute toxicity, tumor response, and long-term survival in patients with advanced nasopharyngeal carcinoma

Detailed Description
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Control group: Neoadjuvant chemotherapy with tri-weekly PF × 3 cycles (cisplatin 100 mg/m2, day 1, followed by 5-FU 1000 mg/m2/d, days 1-4 continuous iv infusion, repeated every 3 weeks) + IMRT ≧ 70 Gy/35 fractions Test group: Neoadjuvant chemotherapy with weekly P-FL × 10 weeks (cisplatin 60 mg/m2 at days 1, 15, 29, 43, 57; alternatively with 5-FU 2500 mg/m2 + Leucovorin 250 mg/m2 at days 8, 22, 36, 50, 64) + IMRT ≧ 70 Gy/35 fractions

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: Cisplatin
* Drug: Fluorouracil
* Radiation: Radiation therapy
* Drug: Leucovorin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological proven NPC. 2010 AJCC stage II-IVB. Age ≧ 20 years old. Performance status of ECOG ≦ 2. Adequate liver, renal, and bone marrow functions 5-1 Serum total bilirubin level ≦ 2.5 mg/dl. 5-2 Serum creatinine ≦ 1.6 mg/dl or calculated CCr ≧ 60 cc/min. 5-3 WBC ≧ 3,000/ul 5-4 Platelet count ≧ 100,000/ul Signed informed consent. Exclusion Criteria: Presence of distant metastasis. Previous radiotherapy or chemotherapy. History of a malignancy except those treated with curative intent for skin cancer (other than melanoma), in situ cervical cancer, ductal carcinoma in situ (DCIS) of the breast. Severe cardiopulmonary diseases (unstable angina and/or congestive heart failure or peripheral vascular disease requiring hospitalization within the last 12 months; chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization) or clinically significant psychiatric disorders. Female patients who are pregnant or lactating.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Control group<br>Neoadjuvant chemotherapy with tri-weekly cisplatin plus fluorouracil × 3 cycles (cisplatin 100 mg/m2, day 1, followed by fluorouracil 1000 mg/m2/d, days 1-4 continuous iv infusion, repeated every 3 weeks) + Intensity-Modulated Radiation Therapy ≧ 70 Gy/35 fractions | Drug: Cisplatin<br>* Neoadjuvant chemotherapy regimen with cisplatin<br>* Other names: CDDP;Drug: Fluorouracil<br>* Neoadjuvant chemotherapy regimen with Fluorouracil<br>* Other names: 5-FU;Radiation: Radiation therapy<br>* Intensity-Modulated Radiation Therapy<br>* Other names: IMRT;|
| Active Comparator: Test group<br>Neoadjuvant chemotherapy with weekly cisplatin, fluorouracil and leucovorin × 10 weeks (cisplatin 60 mg/m2 at days 1, 15, 29, 43, 57; alternatively with fluorouracil 2500 mg/m2 + leucovorin 250 mg/m2 at days 8, 22, 36, 50, 64) + Intensity-Modulated Radiation Therapy ≧ 70 Gy/35 fractions | Drug: Cisplatin<br>* Neoadjuvant chemotherapy regimen with cisplatin<br>* Other names: CDDP;Drug: Fluorouracil<br>* Neoadjuvant chemotherapy regimen with Fluorouracil<br>* Other names: 5-FU;Radiation: Radiation therapy<br>* Intensity-Modulated Radiation Therapy<br>* Other names: IMRT;Drug: Leucovorin<br>* Neoadjuvant chemotherapy regimen with Leucovorin<br>* Other names: Calcium folinate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response by RECIST version 1.1 | According to RECIST version 1.1 | 5 years | 
| Overall survival |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute toxicity by CTCAE deifnition | According to CTCAE deifnition | 6 months |