背景：我們進行了一項多中心、隨機對照的 III 期臨床試驗(NCT02143388)，以研究在高風險局部晚期鼻咽癌（LANPC）患者中，除了同時進行順鉑和放療(CCRT)外，輔助卡培他濱(AC)與單獨使用 CCRT 相比的療效和毒性，該研究表明同步放化療後加卡培他濱輔助治療能有效延長疾病控製。

Background: We conducted a multicenter, randomized controlled phase III clinical trial (NCT02143388) to investigate the efficacy and toxicity of adjuvant capecitabine (AC) in addition to concurrent cisplatin and radiotherapy (CCRT) compared to CCRT alone in high-risk locoregionally advanced nasopharyngeal carcinoma (LANPC) patients.

方法：這項多中心、隨機 III 期臨床試驗入組患者為第 7 版 AJCC/UICC 分期 III-IVb 期並具備下列特征之一:T3-4N2、T1-4N3、治療前血漿 EBV-DNA>20000copy/ml、原發性腫瘤總體積(GTVnx)＞30cm3、原發性腫瘤或多頸部淋巴結轉移瘤大於 4cm 且 SUVmax＞10。2014.3 至 2018.7 月間,招募的 180 例患者按 1:1（90:90）的比例隨機分配接受順鉑同步放化療 ( 順鉑， 100mg/m2,d1, 每 21 天一個周期 ,2-3 個周期 ) ，然後接受卡培他濱輔助化療(1000mg/m2,d1-14,每 21 天一個周期,共 8 個周期)，即 CCRT+AC 組；或單獨接受相同方案的同步放化療，即 CCRT 組。局部放療劑量為 PTVnx ：68~72 Gy/30~32F; PTVnd: 60-68 Gy/30-32F; PTVhigh-risk: 60-64Gy/30-32F; PTVlow-risk: 54-58Gy/30-32F。

Methods: Eligibility criteria included AJCC/UICC 7th ed TNM stage III-IVb and one of the following features: T3-4N2 or T1-4N3 or pre-treatment plasma EBV DNA concentration of >20,000 copy/ml or gross primary tumor volume (GTVnx) of >30 cm3 or a maximum standard uptake value (SUVmax) of >10.0 by 18FDG PET-CT within the primary tumor or multiple neck node metastases, with any larger than 4 cm. All patients were randomly assigned in a 1:1 ratio to receive CCRT (3-weekly cisplatin at 100 mg/m2 for 2-3 cycles) followed by AC (1000 mg/m2 bi-daily for 14 days every 21-day cycle for 8 cycles), or CCRT alone. The prescribed radiation doses were 68-72 Gy/30-32 fractions to the PTVnx, 60-68 Gy/30-32 fractions to PTVnd, 60-64Gy/30-32 fractions to PTVhigh-risk, 54-58Gy/30-32 fractions to PTVlow-risk. Primary end point was failure-free survival (FFS).

結果：整個治療過程中，所有患者均完成了 2 個周期的同步順鉑放化療(順鉑的累積劑量強度均為 200mg/m2)。 85 例(94.4%)患者繼續接受 AC 治療，71 例(78.9%)患者完成 8 個周期；19 例(22.4%)患者 AC 治療減量。中位隨訪 44.8 個月，CCRT+AC 組 3 年 FFS 顯著優於 CCRT 組(87.7% vs 73.3%；HR: 0.52 [95%CI: 0.29-0.77]，P=0.037)。總的來說，3-y OS、3-y DMFS 和 3 年無局部複發生存（3-y LFS）分別為 92.6% vs 88.9% (HR [95% CI]: 0.66 [0.28-1.59]), 88.8% vs. 81.1% (HR:0.67 [0.33-1.33])和 91.5% vs 80.0% (HR: 0.50 [0.25-1.00])。3~4 級急性不良事件在 CCRT+AC 組為 57.8%(52/90)，在 CCRT 單獨組為 51.1%(46/90)，CCRT+AC 組的手足綜合征(3.5% vs 0%)、口幹燥症(11.1% vs 3.3%)、粘膜炎(23.3% vs 16.7%)和貧血(5.6% vs 2.2%)的發生率較高。3~4 級不良事件分別為13.3%(12/90)和 9.0%(8/89)。

Results: Between Mar 2014 to Jul 2018, 180 patients were recruited (90 patients in CCRT+AC arm and 90 in CCRT alone arm). All patients completed RT and ≥2 cycles of concurrent cisplatin in both treatment arms (cumulative dose intensities for cisplatin were 200 mg/m2 in both arms). 85 (94.4%) patients went on to receive AC, with 71 (78.9%) patients completing 8 cycles; 19 (22.4%) patients had dose reduction of AC. With a median follow-up of 44.8 mo, the 3-y FFS was significantly superior in the CCRT+AC arm than the CCRT arm for the intention-to-treat cohort (87.7% vs 73.3%; HR: 0.52 [95% CI: 0.29-0.77], P = 0.037). 3-year overall, distant metastasis-free and locoregional relapse-free survival were 92.6% vs 88.9% (HR [95% CI]: 0.66 [0.28-1.59]), 88.8% vs. 81.1% (HR: 0.67 [0.33-1.33]) and 91.5% vs 80.0% (HR: 0.50 [0.25-1.00]), respectively. Incidences of G3-4 acute toxicities were 57.8% (52 of 90) in CCRT+AC arm and 51.1% (46 of 90) in CCRT alone arm, with a higher incidence of hand foot syndrome (3.5% vs 0%), xerostomia (11.1% vs 3.3%), mucositis (23.3% vs 16.7%), and anemia (5.6% vs 2.2%) in the CCRT+AC arm. G3-4 late toxicities occurred in 13.3% (12 of 90) and 9.0% (8 of 89), respectively.

結論：在高危 LANPC 中，同步放化療後予以卡培他濱輔助化療比單獨同步放化療有更好的疾病控製率。

Conclusions: The addition of capecitabine to CCRT conferred a superior disease control than CCRT alone in high-risk LANPC. Survivals in ITT and PP set.