Gastrointestinal Cancer

Learning Objectives After completing this course, the reader will be able to: 1. Discuss the epidemiology of esophageal cancer. 2. Explain the current status of diagosing and treating esophageal cancer. 3. Describe potential novel targets for new drug development in esophageal cancer. Abstract Esophageal cancer is a highly aggressive neoplasm. In 2005, 14,520 Americans will be diagnosed with esopha-geal cancer, and more than 90% will die of their disease. On a global basis, cancer of the esophagus is the sixth leading cause of cancer death worldwide. In fact, gastric and esophageal cancers together accounted for nearly 1.3 million new cases and 980,000 deaths worldwide in 2000—more than lung, breast, or colorectal cancer. Although esophageal squamous cell carcinoma cases have steadily declined, the incidence of gastroesopha-geal junction adenocarcinoma has increased 4%–10% per year among U.S. men since 1976, more rapidly than for any other cancer type, and parallels rises in population trends in obesity and reflux disease. With advances in surgical techniques and treatment, the prognosis of esophageal cancer has slowly improved over the past three decades. However, the 5-year overall survival rate (14%) remains poor, even in comparison with the dismal survival rates (4%) from the 1970s. The underlying reasons for this disappointingly low survival rate are multifold: (a) ineffective screening tools and guidelines; (b) cancer detection at an advanced stage, with over 50% of patients with unresectable disease or distant metastasis at presentation; (c) high risk for recurrent disease after esophagectomy or definitive chemoradiotherapy; (d) unreliable noninvasive tools to measure complete response to chemoradiotherapy; and (e) limited survival achieved with palliative chemo-therapy alone for patients with metastatic or unresect-able disease. Clearly, additional strategies are needed to detect esophageal cancer earlier and to improve our systemic treatment options. Over the past decade, the field of drug development has been transformed with the identification of and ability to direct treatment at specific molecular targets. This review focuses on novel targeted treatments in development for esopha-geal squamous cell carcinoma and distal esophageal and gastroesophageal junction adenocarcinoma. The Oncologist 2005:590–601 Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com CME CME