Treatment Decisions After Diagnosis of Metastatic Colorectal Cancer

Treatment of metastatic colorectal cancer (mCRC) involves the use of active cytotoxic drugs (irinotecan, oxaliplatin, 5-fluorouracil [5-FU], and capecitabine) and biological agents (bevacizumab, cetuximab, and panitumumab) either in combination or as single agents. Until recently, the only biological agent with proven first-line efficacy was bevacizumab, but options have expanded from the data generated with anti-endothelial growth factor (EGFR) monoclonal antibodies. Anti-EGFR agents can be added to first-line FOLFIRI (5-fluorouracil, leucovorin [folinic acid], irinotecan) or FOLFOX (5-fluorouracil, leucovorin [folinic acid], oxaliplatin) in patients whose tumors express wild-type KRAS. These agents may improve outcomes when added to chemotherapy, particularly progression-free survival (PFS), and in the case of cetuximab, overall survival (OS) and response rates. The selection of first-line therapy should be based on the individual treatment goals after considering the efficacy and tolerability of each regimen. For patients with metastases confined to the liver, surgical resection offers a potentially curative approach. For initially unresectable lesions, treatment regimens offering high response rates may produce sufficient tumor shrinkage to permit complete resection. Regimens with high response rates are also preferable for patients requiring symptom relief or for those with large tumor burdens. The choice between intensive vs. nonintensive management also depends on other factors, including the patient's functional status, comorbidities, and desires. A sequential single-agent strategy or an intermittent approach (combination therapy followed by maintenance) may minimize toxicity and be appropriate for patients who are not surgical candidates, irrespective of treatment response. Guidelines, such as those of the National Comprehensive Cancer Network (NCCN), recommend that KRAS mutational status should be determined at mCRC diagnosis to identify candidates for anti-EGFR therapy whether they are used in first or subsequent lines of treatment.