Current issues in rectal cancer chemotherapy.

Purpose: In this review we intend to provide a synthesized review of relevant studies and articles relating to the use of chemotherapy in the treatment of rectal cancer. The focus will be on the adjuvant and neoadjuvant treatment of stage II and III rectal cancer. The importance of risk stratification in the decisions to treat rectal cancer, both through clinical evaluation of patients as well as molecular analysis of tumors will be reviewed. Symptomatology associated with rectal cancer and rectal cancer therapy will be discussed as an increasingly important element of trial design. Additionally, new agents in the treatment of rectal cancer will be discussed. Finally, the design of 2 current studies incorporating these issues in their trial design will be presented. Methods: A MEDLINE search for clinical trials and reviews was performed, with selection of the most relevant clinical trials pertaining to the treatment of rectal cancer with chemotherapeutic agents. Results: Adjuvant and neoadjuvant treatments with chemotherapeutic agents have served to improve rates of local recurrence as well as overall survival. Trials evaluating the efficacy of orally active fluoropyrimidines, newer generation platinum agents, and inhibitors to vascular endothelial growth factors in the treatment of rectal cancer are currently underway. Conclusions: The large U.S. trials that are currently underway will provide answers to several outstanding questions, including the efficacy of orally active fluoropyrimidines, newer generation platinum agents, and inhibitors to vascular endothelial growth factors in rectal cancer. These trials will also include rigorous assessments of symptomatology by validated symptom measures, as well as the evaluation of molecular tumor markers and their correlation with outcomes. Finally, the identification of low-risk groups of patients who do not require radiotherapy remains an important question in the treatment of rectal cancer.