Efficacy and safety of schedule-modified oral capecitabine/S-1 as maintenance therapy for stage N3 nasopharyngeal carcinoma after definitive chemoradiotherapy: a multicentre, single-arm phase II clinical trial

BACKGROUND AND PURPOSE: N3 nasopharyngeal carcinoma (NPC) continues to demonstrate high distant metastasis rates despite aggressive treatment. This phase II trial evaluated schedule-modified oral maintenance chemotherapy with capecitabine or S-1 following definitive chemoradiotherapy in this high-risk population. METHODS: In this multicenter, single-arm study, patients with non-metastatic N3 NPC received induction chemotherapy (gemcitabine/nedaplatin) followed by concurrent definitive chemoradiotherapy (nedaplatin). Within one month post-radiotherapy, patients initiated 12 cycles of oral maintenance therapy (capecitabine 1250 mg/m² twice daily or S-1 body surface area based dosing, days 1-14, every 28 days). Primary endpoint was 2-year progression-free survival (PFS). RESULTS: Among 115 enrolled patients, after 46.2 months median follow-up, 2-year PFS reached 92.0% (95% CI: 87.1-97.2). The 2-year overall survival, locoregional recurrence-free survival, and distant metastasis-free survival rates were 98.3%, 98.1%, and 92.9%, respectively. Maintenance therapy demonstrated favorable tolerability with only 7.0% grade 3 adverse events and no grade 4/5 events. Notably, 78.3% of patients completed all 12 maintenance cycles. CONCLUSION: Schedule-modified oral maintenance chemotherapy with capecitabine or S-1 following definitive chemoradiotherapy showed promising efficacy and manageable toxicity in stage N3 NPC, supporting further investigation of this consolidation approach. TRIAL REGISTRATION: ClinicalTrials.gov, Registration number: NCT04220528, Date of registration: January 4, 2020, Retrospectively registered.