Gastrectomy with or without neoadjuvant S-1 plus cisplatin for type 4 or large type 3 gastric cancer (JCOG0501): an open-label, phase 3, randomized controlled trial

Abstract

Background Specific treatment strategies are sorely needed for scirrhous-type gastric cancer still, which has poor prognosis. Based on the promising results of our previous phase II study (JCOG0210), we initiated a phase III study to confirm the efficacy of neoadjuvant chemotherapy (NAC) in type 4 or large type 3 gastric cancer. Methods Patients aged 20-75 years without a macroscopic unresectable factor as confirmed via staging laparoscopy were randomly assigned to surgery followed by adjuvant chemotherapy with S-1 (Arm A) or NAC (S-1plus cisplatin) followed by D2 gastrectomy plus adjuvant chemotherapy with S-1 (Arm B). The primary endpoint was overall survival (OS). Results Between October 2005 and July 2013, 316 patients were enrolled, allocating 158 patients to each arm. In Arm B, in which NAC was completed in 88% of patients. Significant downstaging based on tumor depth, lymph node metastasis, and peritoneal cytology was observed using NAC. Excluding the initial 16 patients randomized before the first revision of the protocol, 149 and 151 patients in arms A and B, respectively, were included in the primary analysis. The 3-year OS rates were 62.4% [95% confidence interval (CI) 54.1-69.6] in Arm A and 60.9% (95% CI 52.7-68.2) in Arm B. The hazard ratio of Arm B against Arm A was 0.916 (95% CI 0.679-1.236). Conclusions For type 4 or large type 3 gastric cancer, NAC with S-1 plus cisplatin failed to demonstrate a survival benefit. D2 surgery followed by adjuvant chemotherapy remains the standard treatment.

Neoadjuvant Chemotherapy with S-1 and Oxaliplatin followed by Laparoscopic D2 Gastrectomy for Clinical Stage III Gastric Cancer: Primary Results of Phase II nacG-SOX130 Study

“…It would be a next challenge to monitor on-treatment efficacy and arrange the scheduled treatment to promote the personalized medicine in neoadjuvant chemotherapy for gastric cancer. The pRR, which was one of the secondary endpoints, was 58.8% (95%CI: 76.8-99.6), and was favorable compared to those in previous studies (48-51%) [17,24,25]. In addition, the conditional pRR of 26.4% by the threshold of 10% of the residual tumor was also favorable compared to those of previous study (15.4-19.4%) [26].…”

“…Primary Results of Phase II nacG-SOX130 Study exactly target the pure neoadjuvant population, i.e. Stage II/III patients [15][16][17]. On the other hand, the proof of principle that other platinum, i.e.…”

Phase II study of neoadjuvant chemotherapy with S-1 plus oxaliplatin for gastric cancer clinical T4 or N2-3

“…JCOG0405, a Phase II study of neoadjuvant CS in patients with gastric cancer and bulky lymph nodes or para-aortic lymph node metastases, reported favorable outcomes, the R0 resection rate being 82% and the 3-year and 5-year survival rates 59% and 53%, respectively [5]. However, the JCOG0501 trial, a phase III study that investigated the e cacy of neoadjuvant chemotherapy with CS in patients with Type 4 or large Type 3 (> 8 cm in maximum diameter) gastric cancers [11], failed to demonstrate that patients who received neoadjuvant CS had better OS than those who underwent upfront surgery [12].…”

Current status and future perspectives on neoadjuvant therapy in gastric cancer

“…Nevertheless, the benefit of NAT differs among regions, and in general, NAT is more preferred in Western countries than in Eastern countries. In Japan, the phase III study JCOG0501 failed to demonstrate the efficacy of preoperative NACT with S-1 plus cisplatin for patients with type 4 or large type 3 (≥8 cm in maximum diameter) GC ( 8 ), with 3-year relapse-free survival (RFS) rates of 60.9% and 62.4% for patients who received preoperative NACT vs. those who did not, respectively (HR, 0.916; 95% CI, 0.679−1.236) ( 9 ). Therefore, NACT is not strongly recommended for GC, with the exception of patients with extensive nodal metastasis, as defined as bulky (≥30 mm in diameter) suprapancreatic lymph nodes or enlarged (≥10 mm in diameter) para-aortic lymph nodes ( 10 ).…”