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Gastric cancer is a major cause of mortality worldwide. Prognosis is poor unless the cancer is diagnosed at a very early stage. In Western countries, the 5-year survival rate is lower than 20%, but, in countries such as Japan, where screening is widespread, the overall survival rate is higher than 60%. Therapeutic options for patients with stage II or III gastric cancer include surgery (with or without adjuvant chemotherapy), radiation therapy, or both.
In Japan, the standard of care for patients with stage II or III gastric cancer has been gastrectomy with extended lymph node dissection and no adjuvant therapy. To evaluate the efficacy of adjuvant chemotherapy in this population, investigators randomized 1059 patients with stage II or III gastric cancer who underwent gastrectomy with extended lymph node dissection to either adjuvant chemotherapy with an oral fluoropyrimidine (S-1) or no therapy. Patients in the active-treatment group received 4 weeks of chemotherapy, separated by 2 weeks with no therapy, for 1 year; all patients were followed for survival and recurrence. Care providers and patients were not blinded to the assigned treatment arm, but the adjudication panel who determined recurrence was. The study endpoints were death and tumor recurrences. Imaging (usually computed tomography) was performed every 6 months for 2 years, and then every year, to identify recurrences.
The multicenter study was stopped after the first interim data analysis (1 year after completion of enrollment goals) by the data and safety monitoring committee, because active treatment exceeded the efficacy threshold. Three-year survival for the active-treatment group was 80.1%, compared with 70.1% for controls (hazard ratio, 0.68; 95% CI, 0.52–0.87; P=0.003). The relapse-free 3-year survival rate was 72.2% for the active-treatment group and 59.6% for controls (HR, 0.62; 95% CI, 0.50–0.77; P<0.001). Serious adverse effects were uncommon. The investigators concluded that the study drug was an effective adjuvant therapy for Asian patients who were undergoing surgery for stage II or III gastric cancer.
Sakuramoto S et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med 2007 Nov 1; 357:1810.
Comment
Comparing this study with those done in Western countries would be difficult because of differences in survival rates, early detection rates, and surgical techniques between Western and Asian countries. However, these data are consistent with those from Western countries that show that adjuvant or neoadjuvant chemotherapy or radiation therapy lengthens survival in patients with gastric cancer. One cannot compare the efficacy of S-1 to the multimodal adjuvant therapy that has been used in other studies, but one can conclude that patients with stage II or III gastric cancer do better with some type of adjuvant therapy than with surgical resection alone. Details of the optimal adjuvant therapy regimen and the expected survival rate probably vary geographically.