Systemic treatment for metastatic or recurrent disease

The majority of patients with esophageal cancer develop metastasis during the course of their disease [1]. Chemotherapy, therefore, remains the mainstay of treatment of patients with advanced esophageal cancer and is predominantly used to prolong survival and preserve quality of life [1]. According to data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program, the 5-year survival for patients with esophageal cancer improved only modestly over the last 50 years, from 4 % in the years 1950-1954 to 12-17 % during the period 1994-2002 and 20 % in 2006 [2]. Despite a large number of clinical trials, there is no consensus as to the best regimen for initial treatment of patients with advanced gastroesophageal cancer. In the majority of cases, chemotherapy for advanced esophageal and esophagogastric junction (GEJ) adenocarcinoma, squamous cell carcinoma of the esophagus, and gastric adenocarcinoma is often used interchangeably [3]. The comparison of chemotherapy versus best supportive care consistently demonstrated signifi cant benefit in overall survival (OS) favoring chemotherapy (hazard ratio [HR] 0.36; 95 % confidence interval [CI] 0.24-0.55), which translates into a benefi t of approximately 6 months [1, 4]. Similarly, the comparison of combination versus single-agent chemotherapy provided evidence for improved OS infavor of combination chemotherapy (HR 0.82; 95 % CI 0.74-0.90) [1]. It remains a matter of debate, however, if combinations of three cytotoxic agents offer any advantage over two-drug combinations [1, 5].