{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T03:05:14Z","timestamp":1771729514999,"version":"3.50.1"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T00:00:00Z","timestamp":1714694400000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013700","name":"National Comprehensive Cancer Network","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Nintedanib is a tyrosine kinase inhibitor with efficacy in bevacizumab-resistant colorectal cancer models. This phase I\/II study evaluated the recommended phase II dose and efficacy of nintedanib and capecitabine in refractory metastatic colorectal cancer.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Key eligibility criteria included refractory metastatic colorectal cancer and ECOG performance status of 1 or lower. The primary endpoint was 18-week progression-free survival (PFS). A 1-sided binomial test (at \u03b1\u2009=\u2009.1) compared the observed 18-week PFS with a historic control of .25.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Forty-two patients were enrolled, including 39 at the recommended phase II dose. The recommended phase II dose was established to be nintedanib 200\u2009mg by mouth twice daily and capecitabine 1000\u2009mg\/m2 by mouth twice daily. The protocol was evaluated for efficacy in 36 patients. The 18-week PFS was 42% (15\/36 patients; P\u2009=\u2009.0209). Median PFS was 3.4\u2009mo. Median overall survival was 8.9\u2009mo. Sixteen (44%) patients experienced a grade 3\/4 adverse event, most commonly fatigue (8%), palmoplantar erythrodysesthesia (8%), aspartate aminotransferase elevation (6%), asthenia (6%), pulmonary embolus (6%), and dehydration (6%). Osteopontin levels at cycle 1, day 1 and cycle 3, day 1 as well as \u0394CCL2 levels correlated to disease control at 18\u2009weeks.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The combination of nintedanib and capecitabine is well tolerated. Clinical efficacy appears to be superior to regorafenib or tipiracil hydrochloride monotherapy. Further investigation of similar combinations is warranted.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>ClinicalTrials.gov identifier<\/jats:title>\n                  <jats:p>NCT02393755<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jncics\/pkae017","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T00:01:42Z","timestamp":1714694502000},"source":"Crossref","is-referenced-by-count":6,"title":["A phase I\/II study of nintedanib and capecitabine for refractory metastatic colorectal cancer"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4213-8847","authenticated-orcid":false,"given":"Patrick M","family":"Boland","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Rutgers Cancer Institute of New Jersey , New Brunswick, NJ, USA"},{"name":"Department of Medicine, Roswell Park Comprehensive Cancer Center , Buffalo, NY, 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