Esophageal cancer is one of the common malignant tumors, especially in China and the annual incidence of esophageal squamous cell carcinoma is 260,000 with the motility of 210,000. In western countries, the incidence of esophageal adenocarcinoma (esophageal - gastric junction carcinoma) now dramatically increased than in the past. The pathological types of highest incidences are changing from esophageal squamous cell carcinoma (Esophageal Squamous Cell Carcinoma, ESCC) to esophageal adenocarcinoma (Esophageal adenocarcinoma, EAC) whose incidence is about 60-70%. But in Asia, esophageal squamous cell carcinoma is still the dominant pathological type, accounting for more than 95%. The prognosis of esophageal cancer is very poor. About 50% of patients have advanced disease at diagnosis and the natural course is only 6-8 months with a 5-year survival rate of 5-7%. In addition, though some patients received surgical treatment, disease will recurrent and metastasis in nearly 90% of the patients. For those patients in early stage (T1), there are still nearly 50% of patients relapse within 5 years. Therefore, in recent years, doctors and researchers in different countries are continued to seek effective treatment to improve the quality of life of patients with esophageal cancer and prolong survival.

In past decades, there isn't much improvement of the outcome and survival of advanced esophageal cancer due to the lack of effective chemotherapy agents. The traditional chemotherapy drugs to treat esophageal cancer include 5 - fluorouracil and cisplatin and the combination of them results in a 25-35% response rate in both first-line and palliative treatment. And this combing is still the traditional chemotherapy regimens and wildly used in clinical studies to treat both esophageal gland, squamous cell carcinoma of the clinical study.

Paclitaxel plus cisplatin regiment is another promising treatment of esophageal cancer and have been proved effective in a lot of studies. This combination has become a standard treatment of esophageal cancer, especially the esophageal squamous cell carcinoma. In one of our previous study, paclitaxel and cisplatin treatment showed encouraging clinical results with manageable side-effects in 131 patients of advanced esophageal cancer. These investigations have fully proved the efficacy and feasibility of the combination of paclitaxel with cisplatin regiment in the treatment of esophageal cancer. However, the lower solubility of paclitaxel limited its direct intravenous use. To solve this problem, the paclitaxel must inject with an addition of the surfactant polyoxyethylene castor oil. Polyoxyethylene castor oil paclitaxel could induce high incidence of acute hypersensitivity reactions, ie. severe allergic reactions, kidney damage, and neurotoxicity and cardiovascular toxicity which is characterized by axonal degeneration and demyelination. Though proper preventive treatment will greatly reduce the incidence of allergy, there are still a small number of patients have allergy reaction.

As the investigators all know, the main adverse of cisplatin is the renal toxicity. The peak age of esophageal cancer patients are age 65 to 70 and many of them have simultaneously other diseases such as hypertension, diabetes, and chronic kidney disease which cause varying damages of renal function and limit the use of cisplatin in these patients. Therefore, it is urgent and crucial for doctors to seek an alternative of cisplatin in the combination chemotherapy treatment. There haven't well designed large scale clinical trials to evidence the non-platinum treatment in esophageal cancer. Therefore, the investigators designed this randomized clinical trial in which a novel combination of S-1 with paclitaxel is used to treat advanced esophageal cancer patients in compare with paclitaxel/cisplatin and 5-FU/cisplatin treatment to explore its efficacy and toxicity. The investigators hope this study will provide some clues for the treatment of esophageal cancer patients.