From complexity to simplicity: best level of evidence for metastatic colorectal cancer.

Abstract

Simplicity is enormously complex in the treatment of metastatic colorectal cancer. In terms of survival, life expectancy of patients with metastatic colorectal cancer improved substantially from 3 to 6 months in the 1980s when only 5-fluorouracil was available, to more than 20 months today with the availability of various new chemotherapeutic and targeted agents. The use of chemotherapeutic agents — including fluoropyrimidines, irinotecan, and oxaliplatin — has been refined through decades of clinical experience. Maximal exposure, irrespective of sequence, is simply the principle of treating patients through progression with chemotherapy. Targeted therapy has emerged in the past decade, and adds complexity to the treatment principle: survival benefit has been shown with both anti–vascular endothelial growth factor and anti–epidermal growth factor receptor antibodies in individual lines of treatment, but controversy exists as to the best sequence of application. Adding to this complexity, evidence continues to evolve for the predictive value of various key biomarkers as well as the development of new agents, including aflibercept and regorafenib. In this review, the best level of evidence and a simple, yet practical, strategy will be discussed for maximising the overall survival of patients.