The Study On Advanced Esophageal Squamous Cell Carcinoma Patients After Failure Of Chemotherapy:Chemotherapy Or Icotinib

Part Ⅰ:Irinotecan plus fluorouracil-based regimen as second or third-line chemotherapy for recurrent or metastatic esophageal squamous cell carcinoma.Background:No standard second-line regimen exists for the treatment of advanced esophageal squamous cell carcinoma (ESCC). The aim of this study was to evaluate the efficacy and safety of irinotecan and fluorouracil-based chemotherapy as a second or third-line regimen for advanced ESCC patients.Methods:We retrospectively reviewed a cohort of 27 consecutive patients with advanced ESCC in one institute, treated with a combination of irinotecan plus fluorouracil-based regimens after the failure of first-line platinum-based therapy. Nine patients were treated with 150-160 mg/m2 irinotecan and 400mg/m2 fluorouracil (5-FU) on day 1, followed by 2000 mg/m2 5-FU during a 48-hour infusion every two weeks. Eighteen patients received 150-160 mg/m2 irinotecan on day 1 and 80-120 mg/day S-1 on days 1-10 every two weeks. The S-1 dose was based on the patients’body surface areaResults:Twenty-four of the 27 patients were assessable for response. One (3.7%) patient achieved complete response, seven (25.9%) achieved partial response, eight (29.6%) had stable disease, and eight (29.6%) had progressive disease. The median progression-free and overall survival were 4.8 (95% confidence interval [CI]:1.2-8.4) and 10.5 months (95% CI: 8.4-12.7), respectively. Grade 3 neutropenia and diarrhea were detected in four (15%) and one (4%) patient, respectively. No grade 4 toxicity was noted.Conclusions:Our study indicates that an irinotecan plus 5-FU-based regimen is effective and well-tolerated as a second or third-line chemotherapy for patients with advanced ESCC.Part Ⅱ:Predictive value of EGFR overexpression and gene amplification on icotinib efficacy in patients with advanced esophageal squamous cell carcinoma.Background:This study aimed to search for a molecular marker for targeted epithelial growth factor receptor (EGFR) inhibitor Icotinib by analyzing protein expression and amplification of EGFR proto-oncogene in esophageal squamous cell carcinoma (ESCC) patients.Methods:Immunohistochemistry and fluorescence in situ hybridization (FISH) was used to assess EGFR expression and gene amplification status in 193 patients with ESCC. We also examined the association between EGFR overexpression and the efficacy of a novel EGFR TKI, icotinib, in 62 ESCC patients.Results:Of the 193 patients,95 (49.2%) patients showed EGFR overexpression (3+), and 47(24.4%) patients harbored EGFR FISH positivity. EGFR overexpression was significantly correlated with clinical stage and lymph node metastasis (p<0.05). In addition, EGFR overexpression was significantly correlated with EGFR FISH positivity (p<0.001). Among the 62 patients who received icotinib, the response rate was 17.6% for patients with high EGFR-expressing tumors, which was markedly higher than the rate (0%) for patients with low to moderate EGFR-expressing tumors (p=0.341). Furthermore, all cases responded to icotinib showed EGFR overexpression.Conclusions:our study suggests that EGFR overexpression might potentially be used in predicting the efficacy in patients treated with icotinib. These data have implications for both clinical trial design and therapeutic strategies.