S-1 plus docetaxel combination: another adjuvant treatment option for stage III gastric cancer

© Digestive Medicine Research. All rights reserved. Dig Med Res 2022 | https://dx.doi. org/10.21037/dmr-22-50 Despite decades of declining prevalence, gastric cancer (GC) still accounts for over 770,000 cancer-related mortalities worldwide (1). A common therapeutic approach for the treatment of GC involves gastric resection plus with D2 lymph node dissection. However, even following radical surgery, recurrence is typical in the case of locally advanced GC (stage II–III). Postoperative adjuvant chemotherapy trials, which were conducted mainly in Asian patients, confirmed a significant improvement in the survival rate in the adjuvant chemotherapy compared with observation only in resectable GC. Therefore, this surgery-first approach has been strengthened in Asian nations where hematogenous and peritoneal recurrences are common (2). The Japanese ACTS-GC trial was the first positive phase III outcome to address adjuvant chemotherapy with S-1, an oral fluoropyrimidine, as being superior to the “surgery alone” (3). In this trial, 1,059 patients with stage II (excluding T1) or stage III GCs according to the Japanese classification were randomly assigned to the ‘surgery-only’ arm or ‘S-1 treatment’ arm, in which S-1 was administered for a year following D2 gastrectomy. At 3 years, recurrencefree survival (RFS) was 72% in the S-1 arm and 60% in the surgery-only arm [hazard ratio (HR) =0.62; 95% confidence interval (CI): 0.50–0.77; P<0.001], and the overall 3-year survival rates were 80% and 70%, respectively (HR =0.68; 95% CI: 0.52–0.87; P=0.003). However, subgroup analysis revealed that S-1 could only prolong survival in patients with early disease stages (stage II or IIIA) and was unable to prevent hematogenous dissemination (3). Moreover, S-1 is also not widely available worldwide. As a result, in order to improve the clinical outcome, particularly in a more advanced stage IIIB state, it was required to look for a better alternative option, such as one based on a pharmaceutical doublet. In this regard, JACCRO GC-07 study provided an intriguing alternative to S-1 monotherapy (4). The study’s objective was to address whether S-1 plus docetaxel doublet was superior to S-1 alone following R0 resection of pathologic stage III GC. The third English edition of the Japanese Classification of Gastric Carcinoma, which includes stage IIIA (T2N3, T3N2, T4aN1), stage IIIB (T3N3, T4aN2, T4bN0, T4bN1), or stage IIIC (T4aN3, T4bN2, T4bN3), was used to define pathologic stage III GC (5). To briefly summarize the treatment schedule, S-1 was delivered on days 1 through 14 of the first course’s 3-week cycle. After that, patients received intravenous infusions of docetaxel (40 mg/m body surface area) on the first day of each cycle and S-1 (days 1 through 14 of a 3-week cycle) throughout the second to seventh cycle. Patients in the S-1 group received S-1 from days 1 to 28 of a 6-week up to 1 year. The investigators had planned to enroll 1,100 patients between 2013 and 2017, and the second interim analysis was published in 2019 when the number of events reached 216 among 915 enrolled patients. The research revealed that the S-1 plus docetaxel group (n=456) had Editorial Commentary