Systemic therapy for esophageal cancer: chemotherapy.

As one-half of patients with esophagogastric cancer (EGC) present with metastatic disease and the majority of patients with locally advanced disease will eventually develop metastatic disease despite multimodality therapy, most patients will receive palliative chemotherapy at some point. The reference first-line regimen consists of a fluoropyrimidine/platinum combination, which is the standard in East Asia, where this disease is endemic. Options include infusional 5-fluorouracil (5-FU), capecitabine, S-1 and other oral 5-FU pro-drugs and cisplatin or oxaliplatin. The addition of docetaxel to 5-FU/cisplatin is an option for young and fit patients, based on a phase III study, but is associated with significant hematologic toxicity and modest benefit. In the UK, epirubicin is added to the doublet, in the absence of phase III data suggesting a clear benefit; in fact, recent studies suggest no benefit. In the second- and third-line setting, taxanes and irinotecan are now validated options. Overall, improvements on the basis of chemotherapy have been marginal over the last 30 years and current efforts focus on targeted therapies and immunotherapy.