Comparison Of Definitive Chemoradiotherapy In Locally Advanced Esophageal Squamous Cell Carcinoma

BackgroundAs one of the most common gastrointestinal cancer, the incidence of esophageal cancer continues to increase. Esophageal cancer has two main subtypes:esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma, ESCC is the predominant type in China. The most recent estimates in China suggested that 291,238 people was diagnosed with esophageal cancer and that 218,957 people died from the disease in 2011. For inoperable ESCC patient, by now no standardized treatment is performed. Definitive CRT for patients with locally advanced ESCC is therefore a nonsurgical treatment option, and the treatment modalities become a research focus. Thus, to provide these patients efficacious and low toxicity treatment modalities would be urgently desirable.Docetaxel (DTX), an esterified product of 10-deacetyl baccatin Ⅲ, which is extracted from the renewable and more readily available leaves of the European yew tree. DTX binds to microtubules reversibly with high affinity. This binding stabilizes microtubules and prevents depolymerisation from calcium ions. Abundant formation of microtubules and the prevention to replicate leads to apoptosis of tumor cells.S-1 is a novel oral anticancer drug composed of tegafur (FT), gimestat (CDHP), and oteracil potassium (Oxo). CDHP inhibits the activity of dihydropyrimidine dehydrogenase (DPD) that can degrade 5-FU, thereby maintaining prolonged blood and tumor 5-FU concentrations. Following oral administration Oxo is distributed in the gastrointestinal tract at a high concentration prevents phosphorylation of 5-FU by inhibiting the effect of orotate phosphoribosyl transferase (OPRT).ObjectiveThe aim of this study is to estimate the efficacy and toxicity of definitive radiotherapy with concurrent or sequential DTX and S-1 for patients with locally advanced ESCC.MethodsOf the 62 eligible patients enrolled in this study during January 1,2010 to December 31,2014 from Qilu Hospital, Shandong University, Shandong Province,39 patients received 3 cycles of docetaxel/S-1 during and after radiotherapy (concurrent chemoradiotherapy, CCRT), and 23 patients had radiotherapy followed by 3 cycles of docetaxel and S-1 (sequential chemoradiotherapy, SCRT). For statistical analysis, SPSS for Windows (Microsoft) software (version 17.0; SPSS) was used, and a P value of less than 0.05 indicated statistical significance. We use Kaplan-Meier method was used to analyze the survival rate and Log rank test was used to evaluate the difference between two groups.Results1. The CR of CCRT and SCRT groups were 48.72% and 21.74% respectively, p= 0.035.2. The median PFS and OS of all 62 patients were 16.8 months and 29.0 months. The median PFS of CCRT group (23.5 months) was significantly higher than SCRT group (11.7 months), p=0.004. The median OS of CCRT group (33.5 months) was also significantly higher than SCRT group (24.0 months), p=0.004. At 2 years, in this patient population, the rate of PFS of CCRT group was (44.2±8.2%), significantly higher than SCRT group (11.9±9.6%), p= 0.002. The 2-year OS rate of CCRT (68.6±7.5%) was significantly higher than SCRT group as well (42.0±14.0%), p= 0.002.3. Categorical variables and numerical variables in two groups were compared by v2 test and Student’s t test, respectively. The v2 test was used to determine the differences in response rates and adverse events between CCRT and SCRT group. Survival curves were constructed with the Kaplan-Meier method and were analyzed by the log-rank test, p value ￥0.05 was considered statistically significant. We made used of the software package SPSS version 17.0 for the statistical analysis.4. Treatment related adverse events mainly included leukocytopenia, anemia, thrombocytopenia, radiation esophagitis, nausea, vomiting, cutaneous reaction and allergic reaction. The incidence of adverse events was higher in CCRT than SCRT group. There was no G4 or G5 adverse events occurred.ConclusionDefinitive radiotherapy with concurrent or sequential DTX and S-1 for inoperable locally advanced ESCC was very well-tolerated and remarkably active. In both CCRT and SCRT group, acute toxicities were manageable. However, this regimen holds promise for treatment of esophageal carcinoma and warrants further investigation.