A decade of advances in cytotoxic chemotherapy for metastatic colorectal cancer.

Over the past decade treatment for metastatic colorectal cancer (mCRC) has advanced beyond single-agent fluoropyrimidine use to include various cytotoxic combination regimens and novel targeted therapies. Despite the targeted therapy era, traditional cytotoxic agents remain the mainstay of therapy. Improvements in survival in mCRC can be attributed mostly to combination therapy, with enhanced efficacy due to optimization of fluoropyrimidine dosing and the addition of irinotecan and/or oxaliplatin. Despite the enormous progress, few patients with metastatic disease are cured. To realize that ambitious goal we need a better understanding of predictive molecular markers of response, mechanisms of drug toxicity, innate and acquired drug resistance as well as how to optimize cytotoxic agents in combination with newer targeted therapies.