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

作者：Takahashi Naoki; Yamada Yasuhide^*; Furuta Koh; Nagashima Kengo; Kubo Akiko; Sasaki Yusuke; Shoji Hirokazu; Honma Yoshitaka; Iwasa Satoru; Okita Natsuko; Takashima Atsuo; Kato Ken; Hamaguchi Tetsuya; Shimada Yasuhiro

来源：CANCER SCIENCE, 2015, 106(5): 604-610.

DOI：10.1111/cas.12642

• Colorectal cancer
• EGFR
• KRAS
• ligands
• skin toxicity

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 KRASWT 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, 6.4months vs 2.4months, P<0.001; median overall survival, 14.6months vs 7.1months, 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.

• 出版日期2015-5