PMID- 25707609 OWN - NLM STAT- MEDLINE DCOM- 20150825 LR - 20181202 IS - 1349-7006 (Electronic) IS - 1347-9032 (Print) IS - 1347-9032 (Linking) VI - 106 IP - 5 DP - 2015 May TI - Association between serum ligands and the skin toxicity of anti-epidermal growth factor receptor antibody in metastatic colorectal cancer. PG - 604-10 LID - 10.1111/cas.12642 [doi] AB - 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. CI - (c) 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association. FAU - Takahashi, Naoki AU - Takahashi N AD - Division of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan. FAU - Yamada, Yasuhide AU - Yamada Y AD - Division of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan. FAU - Furuta, Koh AU - Furuta K AD - Division of Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan. FAU - Nagashima, Kengo AU - Nagashima K AD - Clinical Research Center, Chiba University Hospital, Chiba, Japan. FAU - Kubo, Akiko AU - Kubo A AD - Division of Pharmacy, National Cancer Center Hospital, Tokyo, Japan. FAU - Sasaki, Yusuke AU - Sasaki Y AD - Division of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan. FAU - Shoji, Hirokazu AU - Shoji H AD - Division of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan. FAU - Honma, Yoshitaka AU - Honma Y AD - Division of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan. FAU - Iwasa, Satoru AU - Iwasa S AD - Division of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan. FAU - Okita, Natsuko AU - Okita N AD - Division of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan. FAU - Takashima, Atsuo AU - Takashima A AD - Division of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan. FAU - Kato, Ken AU - Kato K AD - Division of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan. FAU - Hamaguchi, Tetsuya AU - Hamaguchi T AD - Division of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan. FAU - Shimada, Yasuhiro AU - Shimada Y AD - Division of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan. AD - Division of Medical Oncology, Kochi Health Sciences Center, Kouch, Japan. LA - eng PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150429 PL - England TA - Cancer Sci JT - Cancer science JID - 101168776 RN - 0 (AREG protein, human) RN - 0 (Amphiregulin) RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antineoplastic Agents) RN - 0 (Biomarkers, Pharmacological) RN - 0 (EGF Family of Proteins) RN - 0 (EREG protein, human) RN - 0 (Epiregulin) RN - 0 (HGF protein, human) RN - 0 (KRAS protein, human) RN - 0 (Membrane Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Transforming Growth Factor alpha) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - 6A901E312A (Panitumumab) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases) RN - EC 2.7.1.137 (PIK3CA protein, human) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.11.1 (BRAF protein, human) RN - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf) RN - EC 3.6.1.- (GTP Phosphohydrolases) RN - EC 3.6.1.- (NRAS protein, human) RN - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)) RN - EC 3.6.5.2 (ras Proteins) RN - PQX0D8J21J (Cetuximab) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Amphiregulin MH - Antibodies, Monoclonal/adverse effects/therapeutic use MH - Antibodies, Monoclonal, Humanized/*adverse effects/therapeutic use MH - Antineoplastic Agents/*adverse effects/therapeutic use MH - Biomarkers, Pharmacological/*blood MH - Cetuximab MH - Class I Phosphatidylinositol 3-Kinases MH - Colorectal Neoplasms/*drug therapy/genetics/pathology MH - EGF Family of Proteins/blood MH - Epiregulin/blood MH - ErbB Receptors/*antagonists & inhibitors/immunology/metabolism MH - Female MH - GTP Phosphohydrolases/genetics MH - Hepatocyte Growth Factor/blood MH - Humans MH - Insulin-Like Growth Factor I/analysis MH - Male MH - Membrane Proteins/genetics MH - Middle Aged MH - Mutation MH - Panitumumab MH - Phosphatidylinositol 3-Kinases/genetics MH - Proto-Oncogene Proteins/genetics MH - Proto-Oncogene Proteins B-raf/genetics MH - Proto-Oncogene Proteins p21(ras) MH - Skin/*drug effects/pathology MH - Transforming Growth Factor alpha/blood MH - Treatment Outcome MH - ras Proteins/genetics PMC - PMC4452162 OTO - NOTNLM OT - Colorectal cancer OT - EGFR OT - KRAS OT - ligands OT - skin toxicity EDAT- 2015/02/25 06:00 MHDA- 2015/08/26 06:00 PMCR- 2015/05/01 CRDT- 2015/02/25 06:00 PHST- 2015/01/11 00:00 [received] PHST- 2015/02/16 00:00 [revised] PHST- 2015/02/18 00:00 [accepted] PHST- 2015/02/25 06:00 [entrez] PHST- 2015/02/25 06:00 [pubmed] PHST- 2015/08/26 06:00 [medline] PHST- 2015/05/01 00:00 [pmc-release] AID - 10.1111/cas.12642 [doi] PST - ppublish SO - Cancer Sci. 2015 May;106(5):604-10. doi: 10.1111/cas.12642. Epub 2015 Apr 29.