Association between serum ligands and the skin toxicity of anti‐epidermal growth factor receptor antibody in metastatic colorectal cancer

Cancer Science

Naoki Takahashi²  Yasuhide Yamada¹  Koh Furuta⁵  Kengo Nagashima⁴  Akiko Kubo³  Yusuke Sasaki¹  Hirokazu Shoji¹  Yoshitaka Honma¹  Satoru Iwasa¹  Natsuko Okita¹  Atsuo Takashima¹  Ken Kato¹  Tetsuya Hamaguchi¹ 

[1] Division of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan;ORCID:orcid.org/0000-0001-6377-9507;Division of Pharmacy, National Cancer Center Hospital, Tokyo, Japan;Clinical Research Center, Chiba University Hospital, Chiba, Japan;Division of Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan

关键词: Colorectal cancer;    EGFR;    KRAS;    ligands;    skin toxicity;   

DOI  :  10.1111/cas.12642

来源: Wiley

【 摘 要 】

Abstract

Skin toxicity is a known clinical signature used to predict the prognosis of anti-epidermal growth factor receptor (EGFR) antibody treatment in metastatic colorectal cancer (mCRC). There are no biological markers to predict skin toxicity before anti-EGFR antibody treatment in mCRC patients. Between August 2008 and August 2011, pretreatment serum samples were obtained from KRAS wild-type (WT) patients who received anti-EGFR antibody treatment. Serum levels of ligands were measured by ELISA. A total of 103 KRAS WT patients were enrolled in the study. Progression-free survival and overall survival of patients with a high grade (grade 2–3) of skin toxicity were significantly longer than those with a low grade (grade 0–1) of skin toxicity (median progression-free survival, 6.4 months vs 2.4 months, P < 0.001; median overall survival, 14.6 months vs 7.1 months, P = 0.006). There were significant differences in distribution of serum levels of epiregulin (EREG), amphiregulin (AREG), and hepatocyte growth factor (HGF) between groups of low/high grade of skin toxicity (P < 0.048, P < 0.012, P < 0.012, respectively). In addition, serum levels of HGF, EREG, and AREG were inversely proportional to grades of skin toxicity as determined by the Cochran–Armitage test (P = 0.019, P = 0.047, P = 0.021, respectively). Our study indicated that serum levels such as HGF, EREG, and AREG may be significant markers to predict the grade of skin toxicity and the prognosis of anti-EGFR antibody treatment, which contribute to improvement of the management of skin toxicity and survival time in mCRC patients.

【 授权许可】

CC BY-NC-ND   
© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

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