Efficacy Of Platinum Analogue-based Chemotherapy For Advanced Esophageal Squamous Cell Carcinoma And Prognostic Factors

PartⅠEfficacy of platinum analogue-based chemotherapy for advanced esophageal squamous cell carcinoma and prognostic factorsBackground and objectives:The prognosis of advanced esophageal squamous cell carcinoma(ESCC) was poor.There was no standard chemotherapy regimen for such group of patients. Platinum analogue-based chemotherapy was the most commonly used.The aim of this study was to analyze the outcome of platinum analogue-based chemotherapy for advanced ESCC patients treated in Cancer Hospital of Chinese Academy of Medical Science.The association of response rate or OS and the clinica-lpathological factors were analyzed as well.Methods:Clinical data of 134 advanced ESCC were retrospectively analyzed.All of these chemo-na(i|¨)ve patients received platinum analogue-based chemotherapy.The association of response rate or OS and the clinica-lpathological factors were analyzed.Results:The median age of all the 134 patients was 58 years old.The ratio of male and female was 7.9:1。A total of 450 cycles(median:3 cycles) of chemotherapy was completed.91(67.9%) of these patients received cisplatin-based regimens.The overall response rate was 31.3%,and cisplatin-based regimens were better than other platinum analogue-based regimen,but there was no significant difference(36.3%vs 20.9%,p=0.075).The median follow-up time was 44 months(range 8～120).The median TTP was 4 months(range 1～43),and median survival time was 8 months(range 1～43).The 1 year and 2 year survival rate was 36.2%and 17.5%, respectively.According to univariate analysis,there was a worse prognosis when patients with multiple primary site,well-differentiated tumor,more than one site of metastasis,fail to achieve responses,TTP≤4 months and received less than 2 cycles of chemotherapy.Multivariate analysis showed that TTP≤4 months was the only independent prognostic factor for this group of patients.Conclusions: Platinum analogue-based chemotherapy was the standard of care for advanced ESCC.There was a trend to improve the outcomes with platinum analogue combined with new drugs.Randomized trial with large samples was need.PartⅡPrognostic value of expression of EGFR,HER2,VEGF,ERCC1,MRP1 and LIVIN for platinum analogue-based chemotherapy in advanced ESCCBackground and objectives:The benefit of chemotherapy for advanced ESCC was small.It was important to know what molecular factor can predict the outcome of chemotherapy.The aim of this study was to determine whether expression of EGFR,HER2,VEGF,ERCC1,MRP1 and LIVIN predict clinical outcome in patients of ESCC treated with platinum analogue-based chemotherapy.Methods:The study population consisted of 57 advanced ESCC patients.Patients were treated with platinum analogue-based chemotherapy.The expression of EGFR,HER2,VEGF,ERCC1,MRP1 and LIVIN were examined by immunohistochemistry.Results:The positive rates of EGFR,HER2,VEGF,ERCC1,MRP1,LIVIN were 45.7%,15.8%,24.6%,47.4%,28.1%,43.9%,respectively.The median follow-up time was 3 years.The median survival time was 8 months(range 1～38),median TTP was 3 months(range 1～28).Expression of EGFR,HER2,VEGF,ERCC1,MRP1,LIVIN were not related to response rate and survival.In 29 patients who received Taxans combined with platinum analogue regimen,there was a trend to have longer median overall survival in patients with EGFR overexpression(p=0.189).Conclusions:Immunohistochemical study of EGFR,HER2,VEGF,ERCC1,MRP1,LIVIN showed there was no association between responses to platinum analogue-based chemotherapy and overall survival.There was a trend to have longer overall survival for patients with EGFR overexpression.Further study of the association of EGFR gene amplification and outcome of chemotherapy was warranted. PartⅢPrognostic value of gene amplification and protein expression of EGFR for platinum analogue-based chemotherapy in advanced ESCCBackground and objectives:The aim of this study was to verify the presence of EGFR gene amplification using FISH,and to correlate the results with immunohistochemical expression and clinical-pathological findings and chemotherapy results.Methods:47 ESCC cases were evaluated by immunohistochemistry.The FISH reactioins were performed in 26 cases with EGFP IHC positive(2+) and(3+).Results:The EGFR expression was negative in 2/47 cases(4.3%) and positive in 45 (95.7%),of which 14(29.8%) were 2+ and 12(25.5%) were 3+.No significant associations were found among protein expression,clinicopathological data and overall survival.Among 26 EGFR expression 2+ and 3+ cases,22 showed no gene amplification while 4(15.4%),including one positive(2+) and 3 positive(3+),showed amplification,as demonstrated by FISH.According to univariate analysis,there was a trend to have shorter survival time for patients with gene amplification(p=0.129).Conclusions:Our data demonstrate that expression of EGFR in ESCC was common,and gene amplification was relatively uncommon.Gene amplification was an indicator of poor prognosis in advanced ESCC who treated with platinum analogue-based chemotherapy.