Sequential versus combination therapy in the treatment of patients with advanced colorectal cancer

Colorectal cancer (CRC) remains one of the most frequent cancer diagnoses and a leading cause of cancer-related deaths in the United States. Significant progress, however, has been made since the advent of single-agent 5-fluorouracil therapy. The addition of irinotecan and oxaliplatin to the cytotoxic armamentarium, mostly given in combination, has dramatically improved response rates, progression-free survival, and overall survival (OS). In recent years, the addition of biologic therapies, including bevacizumab, cetuximab, and panitumumab, has further contributed to improved outcomes. There have been recent data suggesting that sequential cytotoxic therapy, in the majority of patients, provides similar outcomes with regard to OS compared with combination chemotherapy. However, because of several limitations in the FOCUS and CAIRO trials, the data are difficult to apply to current treatment regimens. Although these data do help us further define patients who may benefit from sequential chemotherapy, the standard of care remains combination chemotherapy in the vast majority of patients. This approach will be further refined as progress is made in pharmacogenomics and in prognostic and predictive factors in treating patients with metastatic CRC.