Oesophageal cancer: new developments in systemic therapy

Oesophageal cancer is a rare but highly virulent malignancy in the United States and Western countries, and adenocarcinoma of the oesophagus has had the most rapid rate of increase of any solid tumour malignancy. Systemic metastatic disease is present in 50% of patients at diagnosis, and in the remaining 50% of patients presenting initially with loco-regional disease, systemic metastatic disease will develop in the vast majority of these patients. Combined chemotherapy and radiotherapy is the standard of care in the nonsurgical management of oesophageal cancer. Preoperative chemoradiotherapy followed by surgery continues to be actively studied in the surgical management of locally advanced oesophageal cancer. Pathologic complete responses are seen in 20-40% of patients, with five-year survival achieved in 25-35% of patients. The limited efficacy and substantial toxicity of conventional 5-FU-cisplatin-based chemotherapy combined with radiation, or used to treat advanced disease, has prompted the evaluation of newer agents, including the taxanes and irinotecan. These trials have indicated promising antitumour activity and therapy tolerance in both advanced disease and in combined modality therapy trials, depending on the dose and schedule of therapy administered. The advent of newer, targeted therapies, including agents directed against growth factor receptor pathways, tumour angiogenesis, and tumour invasion and metastasis, is leading to a new generation of clinical trials combining these agents with conventional cytotoxic chemotherapy and radiation.