IS3-4 - Phase II Trial of Endostar Combined with Epirubicin, Cisplatin and 5-Fluorouracil in Patients with Advanced and Metastatic Gastric Cancer

Abstract

ABSTRACT Background The aim of this study was to evaluate the efficacy and tolerability of epirubicin, cisplatin, and 5-fluorouracil (ECF regimen) plus a recombinant form of human endostatin, Endostar, for the treatment of patients with metastatic gastric cancer. Methods A two-stage minimax design was employed to estimate the number of patients required in each stratum. According to prior data, the response rate of the modified ECF regimen in first line setting is about 30%, so a response rate of 50% representing an ∼20% improvement was considered sufficient to proceed with further investigation (p0 = 0.3, p1 = 0.5, a = 0.05, b = 0.2).Twenty-five patients with histologically confirmed metastatic gastric adenocarcinoma were treated with a combination of epirubicin 50 mg/m2 on day 1, cisplatin 60 mg/m2 on day 1, 5-fluorouracil 500 mg/m2 on days 1-5, and Endostar 7.5 mg/m2 on days 1-14 every three weeks. Results Total twenty-four of twenty-five patients were assessable for treatment response, and no complete response was observed. After enrolled 20 eligible patients of first line treatment, the study terminated because the response did not reach the criteria of carrying out the second stage.Among the 20 patients who received the regimen as first line therapy, 3 (15%) achieved partial response (PR) and 13 (65%) achieved stable disease (SD). For the total number of patients enrolled, the median survival time was 10.5 months, median progression-free survival was 4.3 months, and the 1-year survival rate was 25%. Grade 3/4 neutropenia, anemia, and thrombocytopenia were observed in 29.6%, 15.7%, and 7.4% of the treatment cycles, and in 68%, 40%, and 20% of the study population, respectively. 12% of patients developed microscopic hematuria, although gross hematuria did not develop. There was no treatment-related death. Conclusions The addition of Endostar to ECF regimen is safe and tolerable, with increased incidence of anemia and thrombocytopenia, but did not improve the response rate in patients with MGC. Further studies are also needed to monitor more closely the incidence of myelosuppression and hematuria when evaluating treatment regimen that includes Endostar.