Metastatic colorectal cancer: Treatment strategies with current cytotoxic regimens

The availability of the cytotoxic agents irinotecan, oxaliplatin, and capecitabine and the targeted biologic agents bevacizumab and cetuximab has dramatically expanded treatment options for patients with metastatic colorectal cancer (mCRC). These agents signaled a new era in the management of mCRC and the possibility of improved outcomes for many patients. In the past, 5-fluorouracil (5-FU) alone or in combination with leucovorin (LV) was the only treatment available for patients with mCRC. Currently, at least five first-line therapies, nine second-line therapies, six third-line therapies, and one fourth-line therapy are available for these patients. No single regimen has emerged as a standard of care for mCRC, challenging oncologists to develop a treatment plan that includes the best integration and sequencing of agents for each patient. Key trials show that both irinotecan and oxaliplatin, when given with infusional 5-FU/LV, are appropriate first-line combination chemotherapy regimens for patients with mCRC. Evidence is also accumulating that exposure to all three cytotoxic agents (5-FU/LV, irinotecan, and oxaliplatin) over the course of treatment can optimize outcomes. Choice of first-line therapy must be based on parameters that include treatment tolerability and impact on later lines of therapy.