Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
JAMA Netw Open. 2022 Feb 1;5(2):e220120. doi: 10.1001/jamanetworkopen.2022.0120.
Multiple paclitaxel-based regimens are widely used in chemoradiation therapy against esophageal cancer, including regimens combining paclitaxel with fluorouracil, cisplatin, and carboplatin. However, which among these 3 regimens provides the best prognosis with minimum adverse events is still unknown.
To compare the efficacy and adverse events of fluorouracil, cisplatin, and carboplatin in definitive chemoradiotherapy in patients with esophageal squamous cell carcinoma (ESCC).
DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial of patients with ESCC was conducted in 11 treatment centers in China. Eligible patients were aged 18 to 75 years and had histologically confirmed ESCC stages IIa to IVa with no prior treatment, Eastern Cooperative Oncology Group performance status of 2 or lower, and adequate organ functions. The study was conducted between July 2015 and February 2018, and the cutoff date for data analysis was August 31, 2020.
Patients with locally advanced ESCC were randomly assigned (1:1:1) to groups combining paclitaxel treatment with fluorouracil, cisplatin, or carboplatin. Patients in the cisplatin group were treated with 2 cycles of concurrent chemoradiotherapy followed by 2 cycles of consolidation chemotherapy with monthly paclitaxel plus cisplatin. For the fluorouracil group, patients were administered 6 cycles of weekly paclitaxel plus fluorouracil in concurrent chemoradiotherapy followed by 2 cycles of monthly paclitaxel plus fluorouracil in consolidation chemotherapy. Patients in the carboplatin group were treated with 6 cycles of weekly paclitaxel plus carboplatin in concurrent chemoradiotherapy followed by 2 cycles of monthly paclitaxel plus carboplatin in consolidation chemotherapy. All patients received radiotherapy of 61.2 Gy delivered in 34 fractions.
The primary end point was overall survival (OS). The secondary end points were progression-free survival and adverse events.
Overall, 321 patients (median [IQR] age, 64 years [59-69 years]; 248 [77.3%] men) with ESCC from 11 centers were randomized into fluorouracil, cisplatin, or carboplatin groups between July 2015 and February 2018. Over a median (IQR) follow-up time of surviving patients of 46.0 months (36.6-53.0 months), the 3-year OS rates were 57.2% in the fluorouracil group, 60.1% in the cisplatin group, and 56.5% in the carboplatin group, respectively (fluorouracil vs cisplatin: HR, 1.06; 95% CI, 0.71-1.60; P = .77; fluorouracil vs carboplatin: HR, 0.94; 95% CI, 0.63-1.40; P = .77). The cisplatin group had significantly higher incidences of acute grade 3 or 4 neutropenia (69 events [60.8%] vs 19 [17.8%] for fluorouracil and 37 [34.6%] carboplatin; P < .001), thrombocytopenia (14 events [13.1%] vs 4 [3.7%] for fluorouracil and 5 [4.7%] for carboplatin; P = .01), anemia (50 events above grade 2 [46.7%] vs 25 [23.4%] for fluorouracil and 37 [34.6%] for carboplatin; P = .35), fatigue (11 events [10.3%] vs 2 [1.9%] for fluorouracil and 1 [0.9%] carboplatin; P = .007), and vomiting (17 events above grade 2 [15.9%] vs 3 [2.8%] for fluorouracil and 5 [4.7%] for carboplatin; P < .001) than the other 2 groups.
In this randomized clinical trial, paclitaxel plus fluorouracil did not show OS superiority over paclitaxel plus cisplatin or paclitaxel plus carboplatin regimens in definitive chemoradiation in patients with locally advanced ESCC. Higher rates of hematologic and gastrointestinal toxic effects were reported in the cisplatin group compared with those in the fluorouracil or carboplatin groups.
ClinicalTrials.gov Identifier: NCT02459457.
多种紫杉醇为基础的方案广泛用于食管癌的放化疗，包括联合氟尿嘧啶、顺铂和卡铂的方案。然而，在这些 3 种方案中，哪种方案能提供最佳预后，同时不良反应最小，目前仍不清楚。
比较氟尿嘧啶、顺铂和卡铂联合紫杉醇在食管鳞状细胞癌（ESCC）根治性放化疗中的疗效和不良反应。
设计、地点和参与者：这是一项在中国 11 家治疗中心进行的 ESCC 患者随机临床试验。符合条件的患者年龄在 18 至 75 岁之间，组织学确诊为 IIa 至 IVa 期的 ESCC，无既往治疗史，东部合作肿瘤组体能状态为 2 或更低，且器官功能充足。研究于 2015 年 7 月至 2018 年 2 月进行，数据分析截止日期为 2020 年 8 月 31 日。
局部晚期 ESCC 患者被随机分配（1:1:1）至联合紫杉醇治疗氟尿嘧啶、顺铂或卡铂的组。顺铂组患者接受 2 个周期的同步放化疗，随后接受 2 个周期的每月紫杉醇加顺铂巩固化疗。氟尿嘧啶组患者接受 6 个周期的每周紫杉醇加氟尿嘧啶同步放化疗，随后接受 2 个周期的每月紫杉醇加氟尿嘧啶巩固化疗。卡铂组患者接受 6 个周期的每周紫杉醇加卡铂同步放化疗，随后接受 2 个周期的每月紫杉醇加卡铂巩固化疗。所有患者均接受 61.2Gy 的放疗，分 34 次进行。
主要终点是总生存期（OS）。次要终点是无进展生存期和不良反应。
共有 321 名（中位[IQR]年龄 64 岁[59-69 岁]；248[77.3%]为男性）来自 11 个中心的 ESCC 患者在 2015 年 7 月至 2018 年 2 月之间被随机分为氟尿嘧啶、顺铂或卡铂组。在幸存患者的中位（IQR）随访时间为 46.0 个月（36.6-53.0 个月），氟尿嘧啶组、顺铂组和卡铂组的 3 年 OS 率分别为 57.2%、60.1%和 56.5%（氟尿嘧啶组与顺铂组：HR，1.06；95%CI，0.71-1.60；P=0.77；氟尿嘧啶组与卡铂组：HR，0.94；95%CI，0.63-1.40；P=0.77）。顺铂组急性 3 级或 4 级中性粒细胞减少症（69 例[60.8%] vs 氟尿嘧啶组 19 例[17.8%]和卡铂组 37 例[34.6%]；P<0.001）、血小板减少症（14 例[13.1%] vs 氟尿嘧啶组 4 例[3.7%]和卡铂组 5 例[4.7%]；P=0.01）、贫血症（2 级以上 50 例[46.7%] vs 氟尿嘧啶组 25 例[23.4%]和卡铂组 37 例[34.6%]；P=0.35）、疲劳（11 例[10.3%] vs 氟尿嘧啶组 2 例[1.9%]和卡铂组 1 例[0.9%]；P=0.007）和呕吐（2 级以上 17 例[15.9%] vs 氟尿嘧啶组 3 例[2.8%]和卡铂组 5 例[4.7%]；P<0.001）的发生率明显高于其他两组。
在这项随机临床试验中，紫杉醇联合氟尿嘧啶方案在局部晚期 ESCC 的放化疗中，与紫杉醇联合顺铂或卡铂方案相比，并未显示出 OS 优势。与氟尿嘧啶或卡铂组相比，顺铂组的血液学和胃肠道毒性反应发生率更高。
ClinicalTrials.gov 标识符：NCT02459457。
