{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T06:14:06Z","timestamp":1764656046333,"version":"3.40.5"},"reference-count":16,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,10,21]],"date-time":"2019-10-21T00:00:00Z","timestamp":1571616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Aflibercept plus 5\u2010fluorouracil\/levofolinate\/irinotecan (FOLFIRI) is a second\u2010line treatment for metastatic colorectal cancer. This ancillary exploratory analysis of data in Japanese people was aimed at exploring the relationship between a set of potential prognostic biomarkers and efficacy endpoints following aflibercept plus FOLFIRI therapy. Sixty\u2010two patients with metastatic colorectal cancer received aflibercept (4\u00a0mg\/kg) plus FOLFIRI every 2\u00a0weeks. Seventy\u2010eight potential protein biomarkers were chosen for analysis based on their roles in angiogenesis, tumor progression, and tumor\u2010stroma interaction. Plasma levels of biomarkers at baseline and at pre\u2010dose 3 (day 1 of treatment cycle 3) were measured in all patients by ELISA. Relationships between these levels and efficacy endpoints were assessed. Ten potential biomarkers had a \u00b130% change from baseline to pre\u2010dose 3 (adjusted <jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>.001), with the greatest changes occurring in placental growth factor (median: +4716%) and vascular endothelial growth factor receptor 1 (+2171%). Baseline levels of eight potential biomarkers correlated with overall survival in a univariate Cox regression analysis: extracellular newly identified receptor for advanced glycation end\u2010products binding protein, insulin\u2010like growth factor\u2010binding protein 1, interleukin\u20108, kallikrein 5, pulmonary surfactant\u2010associated protein D, tissue inhibitor of metalloproteinases 1, tenascin\u2010C, and tumor necrosis factor receptor 2. None correlated with progression\u2010free survival or maximum tumor shrinkage. Pre\u2010dose 3 levels did not correlate with any efficacy endpoints. Preliminary data show that these eight biomarkers could be associated with overall survival. ClinicalTrials.gov identifier: NCT01882868.<\/jats:p>","DOI":"10.1111\/cas.14198","type":"journal-article","created":{"date-parts":[[2019,9,14]],"date-time":"2019-09-14T13:58:35Z","timestamp":1568469515000},"page":"3565-3572","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Exploration of potential prognostic biomarkers in aflibercept plus <scp>FOLFIRI<\/scp> in Japanese patients with metastatic colorectal cancer"],"prefix":"10.1111","volume":"110","author":[{"given":"Tetsuya","family":"Hamaguchi","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology National Cancer Center Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2570-9692","authenticated-orcid":false,"given":"Tadamichi","family":"Denda","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Chiba Cancer Center Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihiro","family":"Kudo","sequence":"additional","affiliation":[{"name":"Osaka University Graduate School of Medicine Suita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naotoshi","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Osaka Medical Center for Cancer and Cardiovascular Disease Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Ura","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology Aichi Cancer Center Hospital Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kentaro","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Oncology Shizuoka Cancer Center Shizuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirofumi","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology Jichi Medical University Hospital Shimotsuke Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Kajiwara","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology Shikoku Cancer Center Matsuyama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takako Eguchi","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology St. Marianna University School of Medicine Hospital Kawasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shin","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Tohoku University Hospital Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Otsu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Oita University Hospital Yufu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshito","family":"Komatsu","sequence":"additional","affiliation":[{"name":"Department of Cancer Center Hokkaido University Hospital Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumio","family":"Nagashima","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Kyorin University Hospital Mitaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7702-122X","authenticated-orcid":false,"given":"Toshikazu","family":"Moriwaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology University of Tsukuba Hospital Tsukuba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9169-8453","authenticated-orcid":false,"given":"Taito","family":"Esaki","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Medical Oncology National Kyushu Cancer Center Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeo","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery Kitasato University East Hospital Sagamihara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michio","family":"Itabashi","sequence":"additional","affiliation":[{"name":"Department of Surgery 2 Tokyo Women's Medical University Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eiji","family":"Oki","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery Kyushu University Hospital Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toru","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Research and development Sanofi K. K. Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marielle","family":"Chiron","sequence":"additional","affiliation":[{"name":"Biomarkers &amp; Imaging Genomics Sanofi Alfortville France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Yoshino","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Oncology National Cancer Center Hospital East Kashiwa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,10,21]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"ToukeiGT.Cancer Registration Statistics. National Cancer Center Japan.http:\/\/ganjoho.jp\/reg_stat\/statistics\/stat\/summary.html. Accessed January 18 2019."},{"key":"e_1_2_8_3_1","unstructured":"American Cancer Society Inc.Survival rates for colorectal cancer by stage.https:\/\/www.cancer.org\/cancer\/colon-rectal-cancer\/detection-diagnosis-staging\/survival-rates.html. Accessed November 17 2018."},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.42.8201"},{"key":"e_1_2_8_5_1","unstructured":"Sanofi.A study of aflibercept versus placebo with FOLFIRI in patients with metastatic colorectal cancer previously treated with an oxaliplatin chemotherapy (AFLAME);2015.https:\/\/clinicaltrials.gov\/ct2\/show\/results\/NCT01661270?sect=X80156. 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