{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T01:37:10Z","timestamp":1774489030543,"version":"3.50.1"},"reference-count":7,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,6,12]],"date-time":"2018-06-12T00:00:00Z","timestamp":1528761600000},"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":["Thoracic Cancer"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Cipatinib is a novel tyrosine kinase inhibitor against both <jats:italic>EGFR<\/jats:italic> and <jats:italic>HER2\/neu<\/jats:italic>. This phase I trial was conducted to assess the safety, dose\u2010limiting toxicities (DLTs), and maximum\u2010tolerated dose of cipatinib in <jats:italic>HER2<\/jats:italic>\u2010positive patients with advanced breast cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eligible adults with advanced breast cancer were administered cipatinib 200 mg\/day (<jats:italic>n<\/jats:italic> = 3) as an initial dose, with escalating dosages of 400 mg (<jats:italic>n<\/jats:italic> = 4), 800 mg (<jats:italic>n<\/jats:italic> = 2), 1200 mg (<jats:italic>n<\/jats:italic> = 3), 1400 mg (<jats:italic>n<\/jats:italic> = 3), 1600 mg (<jats:italic>n<\/jats:italic> = 3), and 1800 mg (<jats:italic>n<\/jats:italic> = 2) in 21 day cycles. DLTs were monitored until the end of cycle 2. Physical examinations, vital signs, blood sampling for hematology, clinical chemistry, and pharmacokinetics were performed throughout the trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 26 subjects enrolled, 23 completed the trial. A total of 143 adverse events (AEs) were reported, of which 87 were associated with cipatinib treatment and comprised: neutropenia (38%), hypertriglyceridemia (15%), fatigue (15%), nausea (12%), fever (19%), and myocardial ischemia (19%). Six AEs were graded 3\u20134 (neutropenia, increases in aspartate aminotransferase, and total bilirubin, fatigue, dizziness and nodal tachycardia), but none of the AEs observed were considered to be DLTs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This tolerability study revealed that despite a mild toxicity profile, cipatinib was well tolerated up to the anticipated maximum dosage of 1800 mg\/m<jats:sup>2<\/jats:sup>. Further clinical trials are warranted.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1759-7714.12784","type":"journal-article","created":{"date-parts":[[2018,6,12]],"date-time":"2018-06-12T07:32:59Z","timestamp":1528788779000},"page":"1041-1047","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Phase I safety and pharmacokinetic study of cipatinib, an original dual tyrosine kinase inhibitor"],"prefix":"10.1111","volume":"9","author":[{"given":"Jiayu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Medical Oncology National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiqun","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuqing","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruigang","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanshan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0234-2747","authenticated-orcid":false,"given":"Binghe","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing 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