A randomized trial to evaluate the effect of epigallocatechin gallate (EGCG) on EBV reactivation in patients with nasopharyngeal carcinoma in remission -the TCOG T2312 study

BACKGROUND: Nasopharyngeal carcinoma (NPC) is associated with Epstein-Barr virus (EBV) infection. Epigallocatechin gallate (EGCG), a major effective compound in green tea extract, inhibits EBV reactivation. We conducted a randomized controlled trial to evaluate the effects of EGCG on EBV reactivation in posttreatment NPC patients in remission status. METHODS: Patients with NPC who received radiation-based treatment and who achieved a complete response with negative plasma EBV DNA results were randomized to receive EGCG or placebo for 3 years. EBV-related antibodies and EBV DNA were monitored periodically. The primary objective was the EBV reactivation rate and the secondary objectives were safety of EGCG and correlation between EBV reactivation and clinical outcomes. RESULTS: A total of 353 patients were included in this study, of whom 327 were evaluable for further analyses. Of these, 161 and 166 patients were randomized to receive EGCG and placebo, respectively. The toxicity of EGCG was minimal and well tolerated. No significant difference was observed in the EBV DNA reactivation or recurrence rate between the two groups. Positive plasma EBV DNA was significantly associated with a high recurrence rate and short recurrence-free survival (RFS) and overall survival (OS) times. CONCLUSION: This study failed to demonstrate the ability of EGCG to reduce EBV reactivation and tumor recurrence in NPC patients in remission. However, the results showed that EBV DNA is a prognostic factor for tumor recurrence, RFS, and OS in these patients. Continuous follow-up of plasma EBV DNA is suggested as a surveillance marker for patients with NPC. (NCT01744587).