CRC is the fourth most frequently diagnosed tumor and the second leading cause of cancer death in the United
States. KRAS mutations occur in 35-45% of metastatic-CRC and preclude responsiveness to cetuximab or panitumumab.
However, less than 20% of KRAS wild-type (wt) patients achieve objective response. Alterations of BRAF/NRAS/
PIK3CA/PTEN, have independently been found to give rise to resistance. The first-line trials with cetuximab
chemotherapy are conflicting, because of the many differences among prospective and retrospective evaluations. In
neoadjuvant regimens, cetuximab with CT obtained a significant and early increase of the RR. In second-line studies
cetuximab improved RR and PFS. In third-line studies cetuximab-irinotecan is associated with a significant advantage in
ORR, mTTP and OS. Cetuximab has not reported any benefit neither in adjuvant nor in trials with bevacizumab. In thirdline
studies cetuximab-irinotecan is associated with a significant advantage in ORR, mTTP and OS. Value of KRAS is
questioned, since a high percentage of KRAS-wt patients has no benefit with cetuximab. More and more data on the
molecular patterns of these tumors underline their biological complexity. Cetuximab treatment is usually well tolerated.
Moreover, toxicity seems to correlate with response to treatment. This patents review focuses on recent advances in the
treatment of CRC with cetuximab including several novel therapeutic protocols of intervention.
Keywords: BRAF, cetuximab, chemotherapy, colorectal cancer, EGFR, KRAS, liver metastasis
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