Randomized phase III trial of gastrectomy with or without neoadjuvant S-1 plus cisplatin for type 4 or large type 3 gastric cancer, the short-term safety and surgical results: Japan Clinical Oncology Group Study (JCOG0501)

Abstract

Background The prognosis of patients with linitis plastica (type 4) and large (≥ 8 cm) ulcero-invasive-type (type 3) gastric cancer is extremely poor, even after extended surgery and adjuvant chemotherapy. Given the promising results of our previous phase II study evaluating neoadjuvant chemotherapy (NAC) with S-1 plus cisplatin (JCOG0210), we performed a phase III study to confirm the efficacy of NAC in these patients, with the safety and surgical results are presented here. Methods Eligible patients were randomized to gastrectomy plus adjuvant chemotherapy with S-1 (Arm A) or NAC followed by gastrectomy + adjuvant chemotherapy (Arm B). The primary endpoint was the overall survival (OS). This trial is registered at the UMIN Clinical Trials Registry as C000000279. Results From February 2007 to July 2013, 300 patients were randomized (Arm A 149, Arm B 151). NAC was completed in 133 patients (88%). Major grade 3/4 adverse events during NAC were neutropenia (29.3%), nausea (5.4%), diarrhea (4.8%), and fatigue (2.7%). Gastrectomy was performed in 147 patients (99%) in Arm A and 139 patients (92%) in Arm B. The operation time was significantly shorter in Arm B than in Arm A (median 255 vs. 240 min, respectively; p = 0.024). There were no significant differences in Grade 2-4 morbidity and mortality (25.2% and 1.3% in Arm A and 15.8% and 0.7% in Arm B, respectively). Conclusions NAC for type 4 and large type 3 gastric cancer followed by D2 gastrectomy can be safely performed without increasing the morbidity or mortality.Human rights statement All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the 1964 Declaration of Helsinki and later versions.Informed consent Informed consent was obtained from all patients for inclusion in the study.

Role of staging laparoscopy for gastric cancer patients

“…In many Japanese institutions, SL is carried out based on the clinical trials of the Japan Clinical Oncology Group (JCOG). JCOG0501 is a randomized controlled trial evaluating the efficacy of neoadjuvant chemotherapy (NAC) for patients with large type 3 (≥8 cm) and type 4 advanced gastric cancer. JCOG 0405 is a phase II clinical trial evaluating the efficacy of NAC for GC patients with bulky lymph node metastases (≥3 cm) or para‐aortic node metastases (PAN).…”

Perioperative chemotherapy for locally advanced gastric cancer in Japan: current and future perspectives

“…(Table 3) In Japan, the standard treatment for locally advanced gastric cancer is surgery with postoperative adjuvant chemotherapy; however, the efficacy of preoperative neoadjuvant chemotherapy has also been investigated for selected patients with expected poor survival outcomes, such as those with scirrhous type (macroscopic type 4) gastric cancer or gastric cancer with extensive lymph node metastasis. The JCOG0501 is a multicenter randomized controlled trial aimed at demonstrating the efficacy of preoperative neoadjuvant chemotherapy with S-1 plus cisplatin for patients with type 4 or large type 3 (≥ 8 cm in maximum diameter) gastric cancer [30]. Unexpectedly, survival outcomes were similar in the two groups, with 3-year RFS rates of 60.9% and 62.4% for patients who received preoperative neoadjuvant chemotherapy versus those who did not, respectively (hazard ratio, 0.916; 95% CI, 0.679-1.236) [31].…”

Medical management of gastric cancer: a 2017 update

“…On the other hand, an ongoing Japanese trial (JCOG0501) compares their standard of care which is surgery followed by adjuvant S-1 chemotherapy, with neoadjuvant cisplatin and S-1 (an oral fluoropyrimidine) [15]. Although results of this trial are highly awaited, different tumor biology in the Japanese population makes it questionable whether they will be implemented in the Western population.…”