Multicenter, randomized double-blind placebo-controlled trial of definitive concurrent chemoradiotherapy plus megestrol acetate/placebo in local-advanced esophageal cancer.

Abstract

275 Background: To determine Quality-of-Life (QoL) improvement by Megestrol Acetate (MA) in local advanced esophageal squamous cell carcinoma (ESCC) with definitive concurrent chemoradiotherapy (DCRT). Secondary aims were to examine the safety and the impact of MA on the efficacy of DCRT. Methods: Patients (with previously untreated T1bN+M0 or T2-4aN0-2M0 ESCC) were randomly assigned at a one-to-one ratio to receive MA or placebo (blind). All received 5-FU based chemotherapy with concurrent radiotherapy (50Gy/25F). QoL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questionnaires at pretreatment and 3, 6, 16 weeks of DCRT. The good status (GS) rate of appetite loss (AL), nausea and vomiting (NV), weight (WT) and performance status (PS) were chosen as predefined primary end points. GS defined as the score were ≤ 0 for AL or NV and ≥ 0 for WE or PS when the designed time points compared with last one. Secondary end points were the comprehensive QoL (remaining items of QLQ-C30 changes analysis at 16th week), myelosuppression (MS), and deep vein thrombosis (DVT). The exploratory end points were the objective response rate (ORR), 1-year overall survival (OS) and progression-free survival (PFS). Results: 84 completed the follow-up and were analyzed from which 120 patients randomly assigned. The GS rates of AL (3th week: P = 0.011; 6th week: P < 0.001; 16th week: P = 0.001), NV (6th week: P = 0.001) and PS (6th week: P = 0.01) were higher in MA than Placebo. There were no statistical differences between MA and Placebo on WT. At 16th week, the change degree analysis shown the fatigue was worse in MA than Placebo ( p = 0.031). There were no differences on MS, DVT, ORR, OS and PFS between two arms. Nevertheless the rate of DVT was slightly higher in MA than Placebo (12.5% vs. 2.8%, P = 0.113). Conclusions: MA is helpful for ESCC patients receiving DCRT as well as the risk of DVT needed be careful.