Significance of biological markers for predicting prognosis and selecting chemotherapy regimens of advanced gastric cancer patients between continuous infusion of 5-FU and a combination of 5-FU and cisplatin

Background: Our previous phase II study of 5-fluorouracil (5-FU) and cisplatin (FP) for treatment of advanced gastric cancer showed that strong immunoreactivity for vascular endothelial growth factor (VEGF) is associated with chemoresponse. Patients with four or five of the favorable phenotypes, p53 (-), bcl-2 (-), gluthathione S-transferase pi (-), thymidylate synthase (-), and VEGF (+), survived longer than those with three or less of these phenotypes. The purpose of this study is to confirm our previous results and to compare the significance of those markers between continuous infusion of 5-FU (5-FUci) and FP. Methods: Pretreatment biopsies from 131 of 210 advanced gastric cancer patients enrolled to JCOG9205 were analyzed immunohistochemically for the presence of the five markers. Results: Median survival times of patients treated with 5-FUci (n = 65) or FP (n = 66) were 216 and 253 days, respectively (P = 0.6953). After FP treatment, patients with four or five favorable phenotypes (n = 20) survived longer than those with three or less favorable phenotypes (n = 46) (334 days and 243 days, respectively; P = 0.0463), and the survival times of 34 and 32 patients with VEGF (-) and (+) were similar (269 days and 253 days, respectively; P = 0.6317). After 5-FUci, 30 patients with VEGF (+) survived for a shorter time than 35 patients with VEGF (-) (142 days and 302 days, respectively; P = 0.0043). Conclusion: The number of favorable phenotypes is prognostic for gastric cancer patients treated with FP, and VEGF has a different impact on survival between treatment with 5-FUci and FP.