Analysis Of Prognostic Factors Of Cisplatinum/Paclitaxe With Cisplatinum/5-fluorouracil As First-line Therapy For Non-surgical Locally Advanced Esophageal Squamous Cell Carcinoma Patients

Background and Purpose: Esophageal carcinoma(EC)is the sixth leading cause of cancer-related deaths and the eighth most common cancer worldwide,and mortality has been increasing year by year.Locally advanced esophageal cancer was defned as clinical stage IB–IIIC in the 7th edition of Union for International Cancer Control TNM classifcation,accounts for more than half of all the esophageal cancers in the world,and esophageal squamous cell carcinoma(ESCC)has been the main target of Japan Clinical Oncology Group studies.For locally advanced ESCC,surgery is the optimal treatment method.However,for most patients who are not eligible for curative intended surgery or have refused surgery when diagnosed,chemotherapy,radiotherapy,or chemoradiotherapy have to be considered as alternative options.Also,previous studies have shown that defnitive concurrent chemoradiotherapy(dCRT)is superior to chemotherapy and radiotherapy alone.In Western countries,the cisplatinum/5-FU regimen has been widely used clinically for many years and now is recommended as the standard treatment for EC.However,many Asian clinicians are reluctant to use these regimens directly in their clinical practice because the majority of the enrolled patients in Western trials had adenocarcinoma,while most of the Asian patients suffer from squamous cell carcinoma.Docetaxel is one of the most promising drugs for esophageal cancer.Several exploratory trials have investigated paclitaxel plus cisplatinum,paclitaxel plus cisplatinum and 5-FU in preoperative and postoperative chemotherapy and have shown promising outcomes.Based on these backgrounds,the aim of this study was to retrospectively evaluate the efficacy and toxicity of definitive concurrent chemoradiotherapy(dCRT)with cisplatinum/paclitaxel versus cisplatinum/5-FU in patients with locally advanced ESCC without surgery and identify prognostic factors for tumor control and survival.Methods: This study retrospectively evaluated 202 patients with locally advanced ESCC treated at Shandong Cancer Hospital between January 2009 and December 2013.All patients initially received dCRT,including platinum and paclitaxel or 5-fluorouracil with concurrent 1.8 or 2-Gy/fraction radiation(total dose,54-60 Gy).The patient population was divided into two treatment groups,study group and control group: 105 patients who received paclitaxel/cisplatinum regimen were allocated to the study group,and 97 patients who received 5-fluorouracil/cisplatinum regimen were allocated to the control group.We compared progression free survival(PFS)and overall survival(OS)by various clinical variables,including prior treatment characteristics,major toxicities(mainly in Grade 3 and 4 hematological)and response to dCRT.We used the receiver operating curve(ROC)analysis to determine the optimal cut off value of clinical stage and radiation dose.The Kaplan-Meier method was used for survival comparison and Cox regression for multivariate analysis.Results: The response rate(RR)of the study group was 52.4% with 18 patients obtained complete response(CR),37 patients obtained partial response(PR),and 7 patients obtained CR,30 patients obtained PR in the control group with a RR of 38.1%(P=0.042).Distant metastasis rate was significantly lower in the study group than that in the control group(18.1% versus 30.9%,P=0.034).Median PFS and median OS in group A were significantly better compared with group B(median PFS,15.9 versus 13.0 months,P=0.016 and median OS,33.9 versus 23.1 months,P=0.014).The 1-and 2-year survival rates of the two groups were 82.9% versus 76.3%,and 61.9% versus 47.4%,respectively.The most common adverse reactions were hematology toxicity and gastrointestinal reaction,and most were the grade 1/2 adverse reactions,the grade 3/4 adverse effects in the study group were significantly increased than that in the control group,however,all the adverse effects were manageable,and no side effects-related deaths occurred among patients in both different groups.Conclusions: Our data showed that patients with locally advanced ESCC in the study group had longer PFS and OS compared with the control group.Paclitaxel/Cisplatinum can be considered as a good candidate chemotherapy regimen for patients with locally advanced ESCC who treated with non-surgical therapy.