Randomized phase III study in EBV positive locally advanced nasopharyngeal carcinoma treated with concurrent chemo-radiotherapy with or without anti-viral drug

Abstract

Background: Nasopharyngeal is relatively prevalent in South East Asia and mainland China, northern Africa and Alaska. For advanced disease, there is a greater than 50% risk of recurrence after radiotherapy (RT) alone, and approx. half of all recurrences are distant failures. A meta-analysis of 6 randomized trials showed that addition of chemotherapy (CT) to RT significantly improved disease-free/ progression-free survival rates by 34% to 40% respectively. Epstein-Barr virus (EBV) has yielded significant insight into pathogenesis of NPC. It is undifferentiated form of NPC that shows most consistent worldwide association with EBV suggesting that targeted approaches should be considered for preventive and therapeutic intervention. The prognostic value of pretreatment EBV DNA viral load for non-endemic areas proved in retrospective study conducted in Italy, disease free survival (DFS) and over all survival (OS) were significantly longer in patients with pre-treatment negative EBV DNA than in positive patients. Antiviral drugs have been used to inhibit EBV replication and target viral DNA polymerase Aim of this study is to define the efficacy of adding anti-viral treatment to eliminate PCR-DNA EBV in patients with NPC. It will also be correlated with the response rate (RR), local control, DFS, and OS. Trial design: Patients and Methods: All patients with diagnosis of nasopharyngeal squamous cell carcinoma, . Patients should have positive PCR-DNA EBV. Patients will receive concurrent chemoradiotherapy which consisted of Cisplatin 40 mg/m2 weekly or 100mg/m2 every 3 weeks with IMRT 70Gy/35 fractions. Randomization to antiviral therapy acyclovir tablets 800 mg/day during the whole course of treatment Or Placebo. We aim to enroll 100 patients for study with 2:1 randomization. Follow up with PCRDNA EBV will be done mid-treatment and immediately after treatment then with usual follow up of the NPC cases.