Chemotherapy of Metastatic Colorectal Cancer

Over the past decade, metastatic colorectal cancer has evolved from a relatively resistant disease to one that is sensitive to a variety of chemotherapeutic drugs and combinations of drugs. During the same period, the median survival of patients with metastatic colorectal cancer increased from approximately 14 months to almost 20 months. First-line chemotherapy prolongs survival and delays the appearance of symptoms and should be considered in patients who are still asymptomatic. Patients with metastatic colorectal cancer and adequate performance status should be treated with a combination of fluorouracil (5-FU) and either oxaliplatin or irinotecan. Bevacizumab, the monoclonal antibody against the vascular endothelial growth factor, has been shown to prolong survival with acceptable toxicity and may be added when available. When the disease recurs, second-line chemotherapy may also prolong survival in appropriately selected patients. Typically, treatment includes 5-FU and one of the drugs not used in the first-line therapy (oxaliplatin or irinotecan). Several oral prodrugs of 5-FU are currently available. Capecitabine, approved in the United States, may be safely substituted for 5-FU in the majority of settings and combinations. Cetuximab is a monoclonal antibody against the epidermal growth factor receptor and is approved both as a single agent and in combination with irinotecan for patients with recurrent disease. This treatment may represent a second-line or third-line option in selected patients. Treatment of patients with isolated liver metastases may also include surgical or other ablative procedures. In carefully selected patients, these modalities add to the efficacy of chemotherapy and may be used with potentially curative intent. However, for the vast majority of patients with metastatic colorectal cancer treatment is palliative.