A phase I/II clinical trial of neoadjuvant docetaxel/oxaliplatin/S‑1 (DOS) combination therapy for gastroesophageal junction adenocarcinoma.

BACKGROUND

Gastroesophageal junction (GEJ) adenocarcinoma is aggressive with poor prognosis. Perioperative chemotherapy has become standard, but the optimal regimen remains uncertain. DOS has shown activity in gastric cancer but has not been prospectively assessed in GEJ adenocarcinoma. This study represents the first prospective trial of DOS as neoadjuvant chemotherapy in patients with resectable GEJ adenocarcinoma.

METHODS

This single-arm, single-center phase I/II trial (UMIN000022210) enrolled patients with cT3-4aN0-3M0 GEJ adenocarcinoma. The phase I part established the recommended docetaxel dose (60 mg/m2); phase II evaluated efficacy and safety. The primary endpoint was R0 resection rate; and secondary endpoints included pathological response, adverse events, and 3-year survival.

RESULTS

Forty-three patients were enrolled; 37 received DOS at the recommended dose. Of these, 83.8% completed all planned cycles. Grade ≥ 3 neutropenia occurred in 81.1%, and febrile neutropenia in 18.9%. The R0 resection rate was 94.6% (35/37; 95% CI, 81.8-99.3). Major postoperative complications occurred in 11.4%, with no operative mortality. Major pathological response was achieved in 40.5% of patients, including a pathological complete response rate of 5.4%. At 3 years, overall survival and relapse-free survival were 84.9% and 64.5%, respectively. Patients downstaged to ypStage 0 or IA had significantly better relapse-free survival than others.

CONCLUSIONS

Neoadjuvant DOS chemotherapy showed high R0 resection rates, acceptable toxicity, and favorable survival in resectable GEJ adenocarcinoma, supporting its potential as a treatment option. These findings provide important evidence from East Asia, where S-1-based regimens remain widely used, and complement Western data on perioperative FLOT therapy.