Relationship between Expression of Vascular Endothelial Growth Factor in Tumor Tissue from Gastric Cancers and Chemotherapy Effects: Comparison between S-1 alone and the Combination of S-1 plus CDDP

Background: We have reported that vascular endothelial growth factor (VEGF) expression in gastric cancers might be a selective marker between 5-fluorouracil (5-FU) and a combination of 5-FU plus cisplatin (CDDP). In this study, the relationship between VEGF expression and effects of S-1 with and without CDDP is investigated. Methods: The subjects were 44 patients treated with S-1 (40 mg/m 2 , twice daily, days 1‐28, repeated every 6 weeks) and 24 patients treated with S-1 plus CDDP (S-1 40 mg/m 2 ,t wice daily, days 1‐21, CDDP, 60 or 70 mg/m 2 , day 8, repeated every 5 weeks). VEGF expression in pretreatment endoscopic biopsy samples was assessed immunohistochemically. Results: Median survival times (MST) of the patients treated with S-1 and S-1 plus CDDP were 344 and 388 days. Among evaluable patients, the response rates of patients with VEGF (þ )a nd (2) tumors to S-1 were 40% (6/15) and 54% (13/24), and to S-1 plus CDDP, 79% (15/19) and 80% (4/5). While the survival of patients with VEGF (2) tumors was slightly longer than those with VEGF (þ) tumors in the S-1 group (MST, 425 versus 308 days, P ¼ 0.42), patients with VEGF (þ) tumors survived remarkably longer than those with VEGF (2) tumors in the S-1 plus CDDP group (MST, 570 versus 333 days, P ¼ 0.19). Conclusion: Similarly to our previous study, it is suggested that the effects of adding CDDP to S-1 might be more remarkable in gastric cancer patients with VEGF (þ) tumors than in those with VEGF (2) tumors. These results should be confirmed in a large phase III study.