A Trial of Adjuvant Chemotherapy in Nasopharyngeal Carcinoma Patients With Residual Epstein-Barr Virus (EBV) DNA Following Radiotherapy

• The standard treatment for nasopharynx cancer is a course of radiotherapy with or without concurrent chemotherapy. This will cure about 80% of patients. For the 20% who developed recurrence or metastases, the prognosis is poor.
• Elevated EBV-DNA in plasma at end of radiotherapy has been shown to predict disease recurrence and may be a marker of subclinical residual disease.
• This study aims to test whether adjuvant treatment with 6 cycles of a modern chemotherapy regimen (gemcitabine and cisplatin combination) can improve the survival of these high risk patients of nasopharynx cancer who have elevated EBV-DNA after completion of their radiotherapy.

Inclusion criteria

• Have given written informed consent, prior to pre-study screening, with the understanding that consent may be withdrawn at any time without prejudice.
• A histological diagnosis of nasopharyngeal cancer (NPC) must have been established at some time and the investigator must review and confirm the diagnosis prior to randomization.
• Loco-regional advanced NPC UICC/AJCC Stages IIB, III, IVA or IVB.
• No evidence of distant metastases in the staging work up at diagnosis.
• Must have detectable plasma EBV-DNA (> 0 copies/ml) at 6-8 weeks after completion of primary RT or chemo-RT
• No clinical evidence of persistent loco-regional disease after primary treatment
• Performance status of ECOG grade 0 or 1.
• Patients must have adequate organ and marrow function as defined below:

leukocytes >3,000/L; absolute neutrophil count >1,500/L; platelets >100,000/L; total bilirubin <1.5 X institutional upper limit of normal; AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal; Creatinine clearance > 50 ml/min

• At least 18 years of age, of either sex.
• If female, must be either (i) post-menopausal or surgically sterilized, or (ii) use a hormonal contraceptive, intra-uterine device, diaphragm with spermicide for the duration of the study and must be neither pregnant nor breast-feeding.

Exclusion criteria

• Hypercalcaemia: calcium >= 2.7 mmol/L (10.8 mg/dL).
• Second primary malignancy (except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin).
• More that 12 weeks after completion of primary radiotherapy.
• Had received prior adjuvant chemotherapy.
• Other serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator).
• Have serious active infection.
• Patients with peripheral or ototoxicity with a grade of greater than 2.
• Pregnant or lactating female subjects and subjects with reproductive potential not implementing adequate contraceptive measures.