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World J Gastroenterol. Jan 14, 2016; 22(2): 887-894
Published online Jan 14, 2016. doi: 10.3748/wjg.v22.i2.887
Biomarkers of skin toxicity induced by anti-epidermal growth factor receptor antibody treatment in colorectal cancer
Akiko Kubo, Hironobu Hashimoto, Naoki Takahashi, Yasuhide Yamada
Akiko Kubo, Hironobu Hashimoto, Division of Pharmacy, National Cancer Center Hospital, Tokyo 104-0045, Japan
Naoki Takahashi, Yasuhide Yamada, Gastrointestinal Oncology Division, National Cancer Center Hospital, Tokyo 104-0045, Japan
Author contributions: Kubo A and Hashimoto H contributed equally to this work, generated the figure and wrote the manuscript; Takahashi N and Yamada Y contributed to the writing of the manuscript and designed the aim of the mini-review.
Conflict-of-interest statement: The authors have declared no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Naoki Takahashi, MD, Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. naoki19800623@gmail.com
Telephone: +81-3-35422511 Fax: +81-3-35423815
Received: May 28, 2015
Peer-review started: June 1, 2015
First decision: September 29, 2015
Revised: October 20, 2015
Accepted: November 30, 2015
Article in press: December 1, 2015
Published online: January 14, 2016
Processing time: 222 Days and 19.5 Hours
Abstract

Skin toxicity is a common symptom of anti-epidermal growth factor receptor (EGFR) antibody treatment and is also a predictive marker of its efficacy in colorectal cancer patients. However, severe skin disorders induced by such antibodies negatively impact on the quality of life of patients and decreases drug compliance during treatment. If we can predict the high-risk group susceptible to severe skin toxicity before treatment, we can undertake the early management of any arising skin disorders and formulate a more accurate prognosis for anti-EGFR antibody treatment. Previous studies have identified molecular markers of skin toxicity induced by anti-EGFR antibody, such as EGFR polymorphisms, the expression of inflammatory chemokines and serum levels of EGFR ligands. A clinical trial was undertaken involving the escalation of cetuximab doses, guided by the grade of skin toxicity observed, such as no or low-grade, in metastatic colorectal cancer (the EVEREST study). The dose escalation of cetuximab was confirmed by a safety profile and had the tendency to achieve a higher response rate in KRAS wild-type patients. A large, prospective randomized trial is now ongoing (EVEREST 2) and the results of this trial may contribute to personalized medicine in KRAS wild-type colorectal cancer patients.

Keywords: Colorectal cancer; Skin toxicity; Epidermal growth factor receptor; Epidermal growth factor receptor polymorphism; Ligand

Core tip: Skin toxicity is a well-known biomarker used in the prognosis of anti-epidermal growth factor receptor (EGFR) antibody treatment of colorectal cancer patients. Previous retrospective studies indicated a change of the polymorphism of EGFR intron-1, chemokines and ligands were predictive markers of skin toxicity induced by anti-EGFR antibody. Such biomarkers used in predicting skin toxicity will enable the earlier management of skin toxicity as well as improve patients’ quality of life; however, further validations of prospective studies are needed. For patients with no/mild skin toxicity, a clinical trial of a dose escalation strategy is under evaluation and ongoing in the form of the EVEREST 2 study.