目的:标准新辅助化疗(NACT)治疗局部晚期食管/胃食管连接部鳞状细胞癌(LAEGSC),5-氟尿嘧啶(5FU)+铂,具有毒性和后勤挑战性;需要替代方案。
方法:塔塔纪念中心III期随机开放标签非劣效性试验,印度,在可切除的LAEGSC中。患者随机分为1:1至3个周期,每周3次铂(顺铂75mg/m2或卡铂AUC6),紫杉醇175mg/m2(第1天)或5FU1000mg/m2连续输注(第1-4天),接下来是手术。
结果:在2014年8月至2022年6月之间,我们招募了420例患者;每组210例。接受紫杉醇+铂治疗的患者(194例(92.3%))明显多于接受5FU+铂治疗的患者(170例[85.9%]),P=.009。5FU+铂引起的≥3级毒性(124[69.7%])高于紫杉醇+铂(97[51.9%])。P=.001。131例(62.4%)5FU+铂与139例(66.2%)紫杉醇+铂,P=.415。紫杉醇+铂导致更高的病理原发肿瘤清除率(33[25.8%])比17[15%];P=.04),病理完全缓解率为21.9%,5FU+铂为12.4%,P=.053。紫杉醇+铂的中位OS为27.5个月(95%CI,18.6-43.5),与5FU+铂相比,不低于27.1个月(95%CI,18.8-40.7);HR,0.89(95%CI,0.72-1.09);P=.346。
结论:新辅助紫杉醇+铂类化疗更安全,结果类似的R0切除,较高的病理肿瘤清除率和非劣质生存率,与5FU+铂金相比。紫杉醇+铂应取代5FU+铂作为NACT用于可切除的LAEGSC。
■CTRI/2014/04/004516。
OBJECTIVE: Standard neoadjuvant chemotherapy (NACT) for locally advanced esophageal/gastroesophageal junction squamous cancer (LAEGSC), 5-fluorouracil (5FU)+platinum, is toxic and logistically challenging; alternative regimens are needed.
METHODS: Phase III randomized open-label non-inferiority trial at Tata Memorial Center, India, in resectable LAEGSC. Patients were randomized 1:1 to three cycles of 3-weekly platinum (cisplatin 75 mg/m2 or carboplatin AUC 6) with paclitaxel 175 mg/m2 (day 1) or 5FU 1000 mg/m2 continuous infusion (days 1-4), followed by surgery.
RESULTS: Between August 2014 and June 2022, we enrolled 420 patients; 210 to each arm. Significantly more patients on paclitaxel + platinum (194 (92.3%)] received all 3 chemotherapy cycles than on 5FU+
platinum (170 [85.9%]), P = .009. 5FU +
platinum caused more grade ≥ 3 toxicities (124 [69.7%]) than paclitaxel +
platinum (97 [51.9%]), P = .001. Surgery was performed in 131 (62.4%) patients on 5FU +
platinum vs 139 (66.2%) on paclitaxel +
platinum, P = .415. Paclitaxel + platinum resulted in higher pathologic primary tumor clearance (33 [25.8%]) vs 17 [15%]; P = .04), and pathologic complete responses in 21.9% compared to 12.4% from 5FU + platinum, P = .053. Median OS was 27.5 months (95% CI, 18.6-43.5) from paclitaxel + platinum, which was non-inferior to 27.1 months (95% CI, 18.8-40.7) from 5FU +
platinum; HR, 0.89 (95% CI, 0.72-1.09); P = .346.
CONCLUSIONS: Neoadjuvant paclitaxel + platinum chemotherapy is safer, and results in similar R0 resections, higher pathologic tumor clearance and non-inferior survival, compared to 5FU + platinum. Paclitaxel +
platinum should replace 5FU +
platinum as NACT for resectable LAEGSC.
UNASSIGNED: CTRI/2014/04/004516.