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) fortreatment of advanced gastric cancer showed that strong immunoreactivity for vascular endothelialgrowth factor (VEGF) is associated with chemoresponse. Patients with four or five ofthe favorable phenotypes, p53 (2), bcl-2 (2), gluthathione S-transferase p (2), thymidylatesynthase (2), and VEGF (þ), 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 significanceof those markers between continuous infusion of 5-FU (5-FUci) and FP.Methods: Pretreatment biopsies from 131 of 210 advanced gastric cancer patients enrolledto JCOG9205 were analyzed immunohistochemically for the presence of the five markers.Results: Median survival times of patients treated with 5-FUci (n ¼ 65) or FP (n ¼ 66) were216 and 253 days, respectively (P ¼ 0.6953). After FP treatment, patients with four or fivefavorable phenotypes (n ¼ 20) survived longer than those with three or less favorable phenotypes(n ¼ 46) (334 days and 243 days, respectively; P ¼ 0.0463), and the survival times of34 and 32 patients with VEGF (2) and (þ) were similar (269 days and 253 days, respectively;P ¼ 0.6317). After 5-FUci, 30 patients with VEGF (þ) survived for a shorter time than 35patients with VEGF (2) (142 days and 302 days, respectively; P ¼ 0.0043).Conclusion: The number of favorable phenotypes is prognostic for gastric cancer patientstreated with FP, and VEGF has a different impact on survival between treatment with 5-FUciand FP