Locally advanced gastric cancer (LAGC) has a poor prognosis. Neoadjuvant chemotherapy can reduce tumor loading, degrade staging and increase possibility of complete resection, thus prolonging the survival of LAGC patients (pts). We conducted a phase II trial to assess the feasibility of SOX regimen in combination with apatinib (an anti-angiogenic agent) as neoadjuvant therapy in LAGC.
This study recruited untreated LAGC pts with pathologically and/or cytologically confirmed adenocarcinoma. Treatment included three 21-day cycles of apatinib (oral, 500 mg qd; discontinued in the last cycle), S-1 (oral, 40-60 mg, bid, day 1-day 14) and oxaliplatin (iv, 130 mg/m2, day 1), followed by radical surgery after 4 weeks. The primary outcome was neoadjuvant therapy related toxicity, and the secondary outcomes included tumor response, R0 resection rate, postoperative pathological evaluation and surgical morbidity. The target sample size was 30 pts.
From Dec 2016 to Apr 2018, 30 eligible pts were enrolled. 70% was males. The median age was 60 years (range 43–73 years). At the cut-off date for data analysis (24th Apr, 2018), 24 pts completed the three cycles of neoadjuvant therapy. One complete response, 17 partial response, 5 stable disease and 1 progressive disease (PD) were achieved, yielding an objective response rate of 75.0% and disease control rate of 95.8%. 23 pts received radical surgery except the one who had PD, and all achieved R0 resection. Of the 23 pts receiving surgery, the first 18 pts had completed the postoperative pathological analysis, and the median tumor regression was 85%. Among the pts who had received at least one dose of the preoperative treatment, the incidence of adverse events (AEs) and grade 3/4 AEs were 96.4% and 32.1%, respectively. The main grade 3/4 AEs included hypertension, leukopenia, diarrhea and oral mucositis (all 7.1%). In regard to surgical morbidity, 6 (26.1%) experienced fever, 1 (4.3%) had a duodenal stump fistula, and 1 (4.3%) had incision fat necrosis. No surgical mortality occurred.
Three-weekly neoadjuvant therapy with apatinib plus SOX followed by radical surgery for LAGC showed acceptable toxicity and promising efficacy.
Clinical trial identification
Chinese Clinical Trial Registry (ChiCTR-OPC-16010061).
Legal entity responsible for the study
Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Digestive Surgery, Shanghai Key Laboratory of Gastric Neoplasms.
Has not received any funding.
There was no editorial assistance.
All authors have declared no conflicts of interest.