Phase 2 trial of neoadjuvant docetaxel, oxaliplatin, and S-1 for clinical stage III gastric or esophagogastric junction adenocarcinoma.

ABSTRACT

Background: Although perioperative treatment has been the standard of care for resectable gastric cancer in the West, postoperative adjuvant chemotherapy is still the standard in Japan. We conducted the first phase 2 trial to investigate the efficacy and safety of neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy for cStage III gastric or esophagogastric junction (EGJ) adenocarcinoma in Japan. Methods: Eligibility criteria included cStage III adenocarcinoma of the stomach or EGJ. Patients received docetaxel (40 mg/m2, day 1), oxaliplatin (100 mg/m2, day 1), or S-1 (80 mg/m2, days 1-14) during a 3-week cycle. After two or three cycles of DOS, patients underwent surgical resection. The primary endpoint was progression-free survival (PFS). Results: Between June 2015 and March 2019, 50 patients were enrolled from four institutions. Of 48 eligible patients (37 gastric and 11 EGJ adenocarcinoma), 42 (88%) completed two or three DOS cycles. Grade 3-4 neutropenia and diarrhea occurred in 69% and 19% of patients, respectively, but there were no treatment-related deaths. R0 resection was achieved in 44 (92%) patients, and the pathological response rate (≥ grade 1b) was 63% (30/48). The 3-year PFS, overall survival, and disease-specific survival rates were 54.2%, 68.7%, and 75.8%, respectively. Conclusion: Neoadjuvant DOS chemotherapy had a sufficient antitumor effect and tolerable safety profile in patients with gastric or EGJ adenocarcinoma. The survival benefit of a neoadjuvant strategy using our DOS regimen should be validated in phase 3 trials.