ABSTRACT
Objective: To investigate the safety and short-term efficacy of apatinib combined with oxaliplatin and S-1 in the conversion treatment for gastric cancer with different types of peritoneal metastasis. Methods: A prospective study "one arm exploratory clinical study of conversion therapy of apatinib with S-1 and oxaliplatin in the treatment of advanced gastric cancer" (clinical registration ChiCTR-ONC-17010430) from medical record database was retrospectively analyzed. Patients aged 18-70 years with gastric cancer peritoneal metastasis confirmed by histology and laparoscopic exploration, and had not receive radiotherapy, chemotherapy, targeted therapy or immunotherapy before were enrolled. Before operation, the patients received 6 cycles of S-1 (80-120 mg/d, d1-d14) and oxaliplatin (130 mg/m(2), d1), and 5 cycles of apatinib (500 mg/d, d1-d21) conversion regimen. Three weeks after chemotherapy, whether the operation was performed or not depending on re-evaluation and patient preference. The main outcome were adverse reactions, and the secondary outcome were objective remission rate (ORR), disease control rate (DCR), and overall survival (OS) rate. The follow-up period was up to May 2020. Results: A total of 27 patients with gastric cancer peritoneal metastasis were enrolled in this study. There were 13 males and 14 females, with a median age of 58 (30-68) years old. There were 9 cases of P1a, 5 cases of P1b, and 13 cases of P1c. There were 14 cases with 1-5 scores of PCI (peritoneal cancer index), and 13 cases with 6 scores or above. The incidence of adverse reactions was 100%. The most common adverse reactions were hematological events including leucopenia (70.4%, 19/27) and granulocytopenia (74.1%, 20/27). Non-hematological adverse events included fatigue (51.9%, 14/27) and oral mucositis (37.0%, 10/27). One patient was withdrawn due to grade 4 thrombocytopenia. Among 26 patients with feasible efficacy evaluation, 18 (69.2%) achieved partial remission, 3 (11.5%) achieved stable disease, and 5 (19.2%) disease progression. The objective remission rate was 69.2% (18/26) and the disease control rate was 80.8% (21/26). Fourteen patients underwent surgery, including 6 patients undergoing R0 resection with the R0 resection rate of 42.9% (6/14). The postoperative pathological response rate was 64.3% (9/14). The follow-up time was 12-40 months, and the follow-up rate was 100%. The 1-year OS rate was 65.2% and the survival time was (14.0±1.7) months. The 1-year OS rates of P1a/P1b group and P1c group were 81.8% and 42.0% respectively, whose difference was statistically significant (P=0.041). The 1-year OS rates of PCI 1-5 group and PCI ≥6 group were 67.3% and 38.5% respectively, whose difference was statistically significant (P=0.022). Conclusion: In the conversion treatment of gastric cancer peritoneal metastasis, the safety of apatinib combined with oxaliplatin and S-1 is acceptable, and this regimen shows a good short-term survival efficacy in patients with P1a/P1b and PCI of 1-5.