背景：局部晚期鼻咽癌（NPC）患者盡管在標準治療（順鉑同步放療，加或不加誘導化療）後臨床完全緩解率很高，但通常會出現疾病複發。額外輔助化療的益處仍不清楚。
Background: Patients suffering from locoregionally advanced nasopharyngeal carcinoma (NPC) commonly develop disease recurrence, despite a high rate of complete clinical remission after standard of care (concurrent cisplatin-radiotherapy, with or without induction chemotherapy). The benefit of additional adjuvant chemotherapy remains unclear.
方法：入組患者為具有高風險局部晚期 NPC(III 期~IVA 期，除外 T3-4N0 和 T3N1)且在明確放化療後無局部複發或遠處轉移的患者，患者在最後一次放療完成後的 12~16 周內隨機分配(1:1)接受卡培他濱（650mg/m2，bid）持續治療 1 年(節拍式卡培他濱組，n=204）或僅僅觀察（標準治療組，n=203)。主要終點是無複發生存率（RFS）。
Methods: Patients with high-risk locoregionally advanced NPC (stage III to IVA, excluding T3-4N0 and T3N1), and with no locoregional disease or distant metastasis after definitive chemoradiotherapy, were eligible. They were randomly assigned (1:1) within 12 to 16 weeks after the last radiation dose to receive either capecitabine at a dose of 650 mg/m2 twice daily for 1 year (metronomic capecitabine group) or observation (standard-therapy group). The primary end point was recurrence-free survival (RFS). The calculated sample size was 201 per group, with an 80% power (two-sided α 0.05) to detect a target hazard ratio (HR) of 0.52.
結果：共有406例患者接受了隨機分組，其中節律性卡培他濱組204例，標準治療組202例。中位隨訪36個月後（相當於從標準治療開始算起的43個月），節拍器卡培他濱組的估計3年RFS為85.9%，而標準治療組為76.5%（意向治療人群；心率0.51，95%置信區間0.32-0.81；P=0.003）。節律性卡培他濱組3級不良事件發生率為17.4%，標準治療組為5.5%；手足綜合征是卡培他濱最常見的不良反應（9.0%）。節律性卡培他濱組出現1例4級中性粒細胞減少。兩組都沒有治療相關的死亡。在治療期間，使用節拍器輔助劑卡培他濱對健康相關的生活質量沒有臨床意義的惡化。
Results: A total of 406 patients underwent randomization, comprising 204 in the metronomic capecitabine group and 202 in the standard-therapy group. After a median follow-up of 36 months (corresponding to 43 months when calculated from the start of standard therapy), the estimated 3-year RFS was 85.9% in the metronomic capecitabine group, as compared with 76.5% in the standard-therapy group (intention-to-treat population; HR 0.51, 95% confidence interval 0.32–0.81; P = 0.003). The incidence of grade 3 adverse events was 17.4% in the metronomic capecitabine group and 5.5% in the standard-therapy group; hand-foot syndrome was the most common adverse event related to capecitabine (9.0%). One grade 4 neutropenia occurred in the metronomic capecitabine group. Neither group sufferd from treatment-related deaths. During treatment, there was no clinically meaningful deterioration of health-related quality of life associated with the use of metronomic adjuvant capecitabine.
結論：在放化療的基礎上加用節律性卡培他濱輔助治療可顯著改善局部晚期鼻咽癌的RFS，安全性可控，且不影響生活質量。
Conclusions: The addition of metronomic capecitabine as adjuvant therapy to chemoradiotherapy significantly improved RFS in locoregionally advanced NPC, with a manageable safety profile and no compromise to quality of life.
