GI Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, USA.
State Institution Russian Scientific Oncology Centre n.a. N.N. Blokhin of RAMS, Moscow, Russia.
Ann Oncol. 2017 Sep 1;28(9):2142-2148. doi: 10.1093/annonc/mdx275.
The effect of histology-based treatment regimen on diffuse gastric adenocarcinoma has not been evaluated in clinical trials. This international phase III trial evaluated the efficacy and safety of S-1 (a contemporary oral fluoropyrimidine)/cisplatin versus 5-fluorouracil (5-FU)/cisplatin in chemotherapy-naïve patients with diffuse-type adenocarcinoma involving the gastroesophageal junction or stomach.
Eligibility criteria included untreated, measurable, advanced diffuse adenocarcinoma confirmed by central pathology and performance status of 0-1. Patients were randomized (2 : 1) to receive S-1/cisplatin or 5-FU/cisplatin. Primary end point was overall survival (OS), and secondary end points were progression-free survival, time to treatment failure, overall response rate, and safety. A multivariable analysis was also carried out.
Overall, 361 patients were randomized (S-1/cisplatin, n = 239; 5-FU/cisplatin, n = 122); half (51%) were men, and median age was 56.0 years. In each group, median number of treatment cycles per patient was 4 (range, S-1/cisplatin: 1-20; 5-FU/cisplatin: 1-30), and dose intensity was >95%. OS was not different in the two groups {median OS with S-1/cisplatin, 7.5 [95% confidence interval (CI): 6.7, 9.3]; 5-FU/cisplatin, 6.6 [95% CI: 5.7, 8.1] months; hazard ratio, 0.99 [95% CI: 0.76, 1.28]; P = 0.9312}. Overall response rate was significantly higher in the S-1/cisplatin than 5-FU/cisplatin group (34.7% versus 19.8%; P = 0.01), but progression-free survival and time to treatment failure were not different. Safety was similar between the 2 groups; however, fewer patients treated with S-1/cisplatin than 5-FU/cisplatin had ≥1 grade 3/4 treatment-emergent adverse event or ≥1 adverse event resulting in treatment discontinuation. One treatment-related death occurred in each group. Slow accrual led to early termination.
These data suggest that S-1/cisplatin and 5-FU/cisplatin are similar in efficacy and safety in untreated patients with advanced diffuse adenocarcinoma of the gastroesophageal junction or stomach. The primary end point was not met.
CLINICALTRIAL.GOV REGISTRATION NUMBER: NCT01285557.
基于组织学的治疗方案对弥漫性胃腺癌的影响尚未在临床试验中得到评估。这项国际 III 期试验评估了 S-1（一种现代口服氟嘧啶）/顺铂与 5-氟尿嘧啶（5-FU）/顺铂在未经化疗的弥漫型腺癌患者中的疗效和安全性，这些患者涉及胃食管交界处或胃的弥漫型腺癌。
入选标准包括未经治疗、可测量、经中心病理学证实的晚期弥漫性腺癌，且表现状态为 0-1 级。患者按 2:1 随机分配接受 S-1/顺铂或 5-FU/顺铂治疗。主要终点为总生存期（OS），次要终点为无进展生存期、治疗失败时间、总缓解率和安全性。还进行了多变量分析。
共有 361 例患者被随机分组（S-1/顺铂组，n=239；5-FU/顺铂组，n=122）；其中一半（51%）为男性，中位年龄为 56.0 岁。在每组中，每位患者的中位治疗周期数为 4 个（范围，S-1/顺铂：1-20；5-FU/顺铂：1-30），剂量强度均>95%。两组患者的 OS 无差异{中位 OS 为 S-1/顺铂组 7.5 [95%置信区间（CI）：6.7，9.3]；5-FU/顺铂组 6.6 [95% CI：5.7，8.1] 个月；风险比为 0.99 [95% CI：0.76，1.28]；P=0.9312}。S-1/顺铂组的总缓解率明显高于 5-FU/顺铂组（34.7%比 19.8%；P=0.01），但无进展生存期和治疗失败时间无差异。两组安全性相似；然而，接受 S-1/顺铂治疗的患者中，治疗相关不良事件≥3/4 级或≥1 级且导致治疗中止的不良事件发生率低于接受 5-FU/顺铂治疗的患者。每组各有 1 例治疗相关死亡。由于入组缓慢，试验提前终止。
这些数据表明，S-1/顺铂和 5-FU/顺铂在未经治疗的胃食管交界处或胃弥漫性腺癌患者中的疗效和安全性相似。主要终点未达到。
NCT01285557。
