Therapeutic Gain by Induction-concurrent Chemoradiotherapy and/or Accelerated Fractionation for Nasopharyngeal Carcinoma

Randomized Trial to Evaluate Therapeutic Gain by Changing Chemoradiotherapy From Concurrent-adjuvant to Induction-concurrent Sequence, and Radiotherapy From Conventional to Accelerated Fractionation for Advanced Nasopharyngeal Carcinoma

The objectives of this clinical study are threefold:

1. To compare the benefits in cancer control and survival obtained from adding induction-concurrent chemotherapy to radiation with those from adding concurrent-adjuvant chemotherapy to radiation.
2. To test whether replacing fluorouracil with Xeloda in combining with cisplatin in the chemotherapy plan will maintain or improve further the chemotherapy benefits while reducing the duration of hospital stay.
3. To see if accelerated fractionation radiotherapy can improve the outcome of patients as compared with conventional fractionation radiotherapy.

1. primary objectives include

   1. comparing induction chemotherapy with Cisplatin + 5-Fluorouracil versus adjuvant chemotherapy with Cisplatin + 5-Fluorouracil(PF-Pvs P-PF)
   2. comparing induction chemotherapy with Cisplatin + Capecitabine versus adjuvant chemotherapy with Cisplatin + 5-Fluorouracil(PX-P vs P-PF)
   3. comparing accelerated fractionation versus conventional fractionation (AF vs CF)radiotherapy.

2. secondary objectives include

   1. comparing induction chemotherapy with Cisplatin + Capecitabine versus induction chemotherapy with Cisplatin + 5-Fluorouracil(PX-P vs PX-P)
   2. Comparing concurrent-adjuvant (CA) versus induction-concurrent (IC) chemotherapy sequence.

Inclusion Criteria:

• histologically proven nasopharyngeal carcinoma for primary treatment with radical intent
• non-keratinizing or undifferentiated type
• stage III-IVB (by AJCC/UICC 6th edition)
• ECOG Performance status less or equal to 2
• Marrow: WBC >= 4 and platelet >=100
• Renal: creatinine clearance >=60
• Informed consent

Exclusion Criteria:

• Primary treatment with palliative intent
• WHO type I squamous cell carcinoma or adenocarcinoma
• Evidence of distant metastases
• Patient is pregnant or lactating
• Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer or other cancer for which the patient has been disease-free for 5 years