NCCN胃癌临床实践指南中国版题库.pptVIP

* * ML17032 trial design – An open label, randomized, international multi-center Phase III study of Xeloda in combination with cisplatin versus 5-FU/cisplatin. The doses evaluated were: Cisplatin: 80mg/m2 3- hour i.v. infusion on d1 with hyperhydration Xeloda: 1 000mg/m2 daily; d1-14 q3 weeks 5-FU: 800mg/m2/day; d1-5 q3 weeks. A total of 316 patients were enrolled: 160 randomized to Xeloda/cisplatin and 156 randomized to 5-FU/cisplatin. The target population was typical for a first-line trial with creatinine clearance 60mL/min and measurable disease according to RECIST criteria. Primary objective: confirm non-inferiority in progression-free survival (PFS) between the two treatment arms. * A superior response rate was observed for Xeloda/cisplatin vs. 5-FU/cisplatin (p=0.030), supporting the general trend to superiority seen in other efficacy endpoints. Tumor responses were assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) specifications. Overall response is the sum of confirmed complete and partial responses. Three complete responses were observed in Xeloda/cisplatin groups vs. 4 complete responses in the 5-FU/cisplatin group. Patients in the Xeloda/cisplatin group had 1.4 times the chance of achieving an overall response compared to patients in the 5-FU/cisplatin group. The results of an independent review did not contradict these findings. * In the per protocol analyses without covariate adjustments, Xeloda/cisplatin was found to be non-inferior to 5?FU/cisplatin; therefore, the primary endpoint of non-inferiority in progression-free survival (PFS) in the ML17032 study was met with high significance. The Kaplan-Meier plot of PFS shows a clear separation of curves for Xeloda/cisplatin after the first month and this trend continues until month 13 when only a few patients were left in the risk sets. The comparison of the hazard ratio (HR) limit of 1.25 shown here is a more rigorous test than that vs. the limit of 1.4, and shows