Metastatic colorectal cancer: Therapeutic options

For the past several decades, the therapy for metastatic colorectal cancer had modest benefits because of the limited therapeutic options. Bolus 5-fluorouracil (5FU) and leucovorin (LV) were the standard of care in the United States until 2002, with a response rate of 25% and a median survival of 10 to 12 months. However, with the advent of new agents, namely oxaliplatin and irinotecan, there has been a dramatic change in the way we treat metastatic colorectal cancer. Based on many well-conducted large randomized trials, we have evidence that combination chemotherapy incorporating oxaliplatin or irinotecan with infusional 5FU/LV is superior to 5FU/LV, with doubling of overall survival (OS) to approximately 20 months. There remains some uncertainty as to the best first-line regimen. This might be irrelevant because studies have shown that OS is dependent on exposure to all the active agents, regardless of the time period of exposure. Bevacizumab, which uses anti-angiogenic strategies, has improved disease-free survival (DFS) and OS when combined with standard chemotherapy and is a vital component of metastatic colorectal cancer therapy. However, there are no data supporting its use past progression. Cetuximab, an epithelial growth factor receptor inhibitor, is mainly used in irinotecan-refractory patients. In spite of all these advances, 5-year OS rates continue to be limited. Patients with curative resection of metastatic disease seem to have longer DFS and better 5-year OS rates. This should be a potential goal for responding patients with upfront unresectable, organ-limited disease.