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Vol 6, No 5 (2010)
Review paper
Published online: 2011-01-19
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The treatment interfering with EGFR in colorectal cancer patients

Marek Z. Wojtukiewicz, Piotr Tokajuk, Ewa Sierko
Onkol. Prak. Klin 2010;6(5):241-254.

open access

Vol 6, No 5 (2010)
REVIEW ARTICLES
Published online: 2011-01-19

Abstract

Over the last decade systemic treatment of colorectal cancer patients has changed considerably. New cytotoxics, such as oxaliplatin, irinotecan and capecitabine have been introduced to everyday clinical practice. More importantly, introduction of targeted therapy aimed at molecular targets present in cancer cells has substantially improved treatment outcomes. Currently, two major strategies of targeted therapy are used in colorectal cancer in routine clinical practice: blocking angiogenesis by using bevacizumab, a monoclonal antibody directed against VEGF and inhibition of the epidermal growth factor receptor (EGFR) by monoclonal antibodies — cetuximab and panitumumab. Results of the studies that evaluated association between histologic grade of malignancy and EGFR expression on colorectal cancer cells have been controversial. Interestingly, clinical studies reported in recent years have not showed unequivocally a significant association between EGFR expression and survival of colorectal cancer patients. Nevertheless, it has been demonstrated in several phase II and III clinical trials that the addition of monoclonal antibodies directed against EGFR to palliative chemotherapy in advanced colorectal cancer patients without a mutation in KRAS gene (wild-type KRAS) leads to significant improvements in response rates and significant prolongation of progression-free survival (and in some trials improvement of overall survival was documented, too). Intriguingly, it has been showed in several studies that using monoclonal antibodies directed against EGFR in combination with chemotherapy for advanced colorectal cancer patients with mutation in KRAS gene (mutant KRAS) has been associated with inferior treatment results. These observations have served as the scientific foundation for introduction of KRAS gene mutation analysis to clinical practice as the first biomarker in targeted therapy of advanced colorectal cancer patients. Results of phase III clinical trials were the basis of current indications of cetuximab and panitumumab. These antibodies are indicated for EGFR-expressing, KRAS wild-type metastatic colorectal cancer, in combination with first-line or second-line chemotherapy, or as a single agents in patients who have failed oxaliplatin- and irinotecan-based therapy and who are intolerant to chemotherapy. Additionally, the activity of EGFR tyrosine kinase inhibitors has been evaluated in several phase I and II clinical trials. The aim of this paper is to review data from prospective randomised clinical trials that assessed targeted therapy directed against EGFR in the treatment of colorectal cancer patients.

Onkol. Prak. Klin. 2010; 6, 5: 241–254

Abstract

Over the last decade systemic treatment of colorectal cancer patients has changed considerably. New cytotoxics, such as oxaliplatin, irinotecan and capecitabine have been introduced to everyday clinical practice. More importantly, introduction of targeted therapy aimed at molecular targets present in cancer cells has substantially improved treatment outcomes. Currently, two major strategies of targeted therapy are used in colorectal cancer in routine clinical practice: blocking angiogenesis by using bevacizumab, a monoclonal antibody directed against VEGF and inhibition of the epidermal growth factor receptor (EGFR) by monoclonal antibodies — cetuximab and panitumumab. Results of the studies that evaluated association between histologic grade of malignancy and EGFR expression on colorectal cancer cells have been controversial. Interestingly, clinical studies reported in recent years have not showed unequivocally a significant association between EGFR expression and survival of colorectal cancer patients. Nevertheless, it has been demonstrated in several phase II and III clinical trials that the addition of monoclonal antibodies directed against EGFR to palliative chemotherapy in advanced colorectal cancer patients without a mutation in KRAS gene (wild-type KRAS) leads to significant improvements in response rates and significant prolongation of progression-free survival (and in some trials improvement of overall survival was documented, too). Intriguingly, it has been showed in several studies that using monoclonal antibodies directed against EGFR in combination with chemotherapy for advanced colorectal cancer patients with mutation in KRAS gene (mutant KRAS) has been associated with inferior treatment results. These observations have served as the scientific foundation for introduction of KRAS gene mutation analysis to clinical practice as the first biomarker in targeted therapy of advanced colorectal cancer patients. Results of phase III clinical trials were the basis of current indications of cetuximab and panitumumab. These antibodies are indicated for EGFR-expressing, KRAS wild-type metastatic colorectal cancer, in combination with first-line or second-line chemotherapy, or as a single agents in patients who have failed oxaliplatin- and irinotecan-based therapy and who are intolerant to chemotherapy. Additionally, the activity of EGFR tyrosine kinase inhibitors has been evaluated in several phase I and II clinical trials. The aim of this paper is to review data from prospective randomised clinical trials that assessed targeted therapy directed against EGFR in the treatment of colorectal cancer patients.

Onkol. Prak. Klin. 2010; 6, 5: 241–254

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Keywords

colorectal cancer; targeted therapy; EGFR; EGFR inhibitors; cetuximab; panitumumab; chemotherapy; predictive factors; KRAS mutation; BRAF mutation

About this article
Title

The treatment interfering with EGFR in colorectal cancer patients

Journal

Oncology in Clinical Practice

Issue

Vol 6, No 5 (2010)

Article type

Review paper

Pages

241-254

Published online

2011-01-19

Bibliographic record

Onkol. Prak. Klin 2010;6(5):241-254.

Keywords

colorectal cancer
targeted therapy
EGFR
EGFR inhibitors
cetuximab
panitumumab
chemotherapy
predictive factors
KRAS mutation
BRAF mutation

Authors

Marek Z. Wojtukiewicz
Piotr Tokajuk
Ewa Sierko

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