Systemic Treatment in Recurrent and Metastatic Unresectable Rectal Cancer

Most patients with recurrent and metastatic rectal cancer cannot be cured. Selected patients with local recurrence or liver and/or lung-limited metastatic disease are sometimes curable with radiation therapy (RT) or surgery. However, for the majority of patients, treatment is palliative and systemic therapy remains the mainstay treatment. Over the last ten years, survival of patients with unresectable metastatic or recurrent rectal cancer has considerably improved. The median survival is about two years due to availability of new chemotherapy regimens and targeted therapies. For decades, 5-fluorouracil (5-FU) was the only active and available agent. Since the year 2000, irinotecan and oxaliplatin were approved. Access to all these three active agents strongly correlates with improved survival. More progress was achieved recently with the development of targeted therapies. Bevacizumab is a monoclonal antibody targeting the vascular endothelial growth factor (VEGF). Cetuximab and panitumumab are two monoclonal antibodies targeting the epidermal growth factor receptor (EGFR). Combinations of these different drugs are now commonly used. In non-curable patients, goals are improvement of survival and quality of life. The purpose of this chapter is to review data from clinical trials evaluating systemic therapy in unresectable recurrent or metastatic rectal cancer. Commonly used chemotherapy regimens and biologic agents will be described as well as their side effects. General principles of treatment and specific treatment recommendations will also be discussed.