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Evolution of nonsurgical therapy for colorectal cancer

Abstract

The management of colorectal cancer (CRC) has changed considerably in the past 15 years with the introduction of multiple novel active therapeutic agents. Chemotherapy regimens combining a fluoropyrimidine with either oxaliplatin or irinotecan are standard first-line and second-line therapy for advanced and metastatic disease. The first-line use of these combinations produces tumor response rates of 50% and a median overall survival of 20 months. Addition of bevacizumab to first-line treatment and addition of cetuximab to salvage therapy for patients who fail to respond to irinotecan have contributed to further increases in tumor response rates and enhanced progression-free survival. Such approaches have produced only marginal overall survival benefits, however, and entail considerable cost. Adjuvant chemotherapy, delivered after surgical resection of the primary tumor, increases cure rates by 10% for stage III disease and 3–4% for stage II disease. Encouraging reductions in local relapse rates have been observed in patients with early rectal cancer who have undergone chemoradiotherapy, and increasingly complex regimens are currently being explored in phase II clinical trials in an attempt to increase both the operability and long-term local control of CRC. The greater the therapeutic choice, the greater the cost (both financial and in terms of toxicity), thus the keener the clinical community becomes to develop biomarkers to select patient populations who will be most likely to benefit from a specific agent.

Key Points

  • Colorectal cancer is a common disease with approximately 1 million new cases diagnosed each year

  • Chemotherapy for advanced disease can palliate symptoms and extend life by 12–18 months

  • Chemotherapy for early disease has increased cure rates by approximately 3–10%, depending on the stage of disease

  • Novel biologic therapies have had modest effect on colorectal cancer outcomes when applied to whole populations

  • In the future, patient selection for therapy on the basis of biological criteria is likely to improve response rates and decrease the toxic effects of therapeutic regimens

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Figure 1: Increasing RRs and OS during the evolution of chemotherapy for advanced colorectal cancer.
Figure 2: The angiogenic switch in tumors.

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Correspondence to David J Kerr.

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Midgley, R., Yanagisawa, Y. & Kerr, D. Evolution of nonsurgical therapy for colorectal cancer. Nat Rev Gastroenterol Hepatol 6, 108–120 (2009). https://doi.org/10.1038/ncpgasthep1337

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