{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T13:58:07Z","timestamp":1776347887622,"version":"3.51.2"},"reference-count":21,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T00:00:00Z","timestamp":1681948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["91959205"],"award-info":[{"award-number":["91959205"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Pyrotinib (an irreversible pan\u2010ErbB small\u2010molecular tyrosine kinase inhibitor) was approved in human epidermal growth factor receptor 2 (HER2)\u2010positive breast cancer and showed great antitumor activity in preclinical studies of gastric cancer (GC). This study was first designed to prospectively assess pyrotinib in pretreated HER2\u2010positive GC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This multicenter, phase I study followed a standard \u201c3\u2009+\u20093\u201d design and included two parts. In the pyrotinib part, pyrotinib was administered orally, once per day at dose levels of 240, 320, 400, and 480\u2009mg. In the pyrotinib plus docetaxel part, patients received pyrotinib (qd, d1\u201021, q3W) combined with docetaxel (60\u2009mg\/m<jats:sup>2<\/jats:sup>, d1, q3W) at dose levels of 240, 320, and 400\u2009mg. Primary endpoints were to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of pyrotinib as monotherapy or coadministered with docetaxel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 25 patients were enrolled and received pyrotinib (<jats:italic>n<\/jats:italic>\u00a0=\u00a015) or pyrotinib plus docetaxel (<jats:italic>n<\/jats:italic>\u00a0=\u00a010). One DLT was observed in pyrotinib monotherapy part (Grade 3 uncontrolled diarrhea after supportive care) and pyrotinib plus docetaxel part (Grade 4 neutropenia and leukopenia). In the pyrotinib monotherapy part, MTD was not reached. Diarrhea, anemia, neutropenia, and leukopenia were the most common treatment\u2010related adverse events (TRAEs). The RP2D for pyrotinib monotherapy was recommended as 400\u2009mg. After combining with docetaxel, the risk of leukopenia and neutropenia was increased. Grade\u2009\u22653 TRAEs were reported for four patients in the monotherapy part and for eight patients in the combination part. Mean <jats:italic>t<\/jats:italic><jats:sub>1\/2<\/jats:sub> was approximately 20\u2009h. Pyrotinib exposure was dose\u2010dependent with a nonlinear relationship versus dose. There were five patients who had confirmed partial response (monotherapy: one each at 240, 400, and 480\u2009mg dose cohort; combination therapy: two at 240\u2009mg dose cohort), resulting in an objective response rate of 21% and 20%, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Pyrotinib alone and combined with docetaxel showed acceptable toxicities in patients with pretreated HER2\u2010positive GC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>This study was registered with <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>, NCT02378389.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.5830","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T04:34:13Z","timestamp":1682051653000},"page":"10704-10714","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Pyrotinib alone or in combination with docetaxel in refractory <scp>HER2<\/scp>\u2010positive gastric cancer: A dose\u2010escalation phase I study"],"prefix":"10.1002","volume":"12","author":[{"given":"Dan","family":"Liu","sequence":"first","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Early Drug Development Center Peking University Cancer Hospital &amp; Institute  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8969-6344","authenticated-orcid":false,"given":"Furong","family":"Kou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Day Oncology Unit Peking University Cancer Hospital &amp; Institute  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jifang","family":"Gong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology\/Early Drug Development Center Peking University Cancer Hospital &amp; Institute  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine Sun Yat\u2010sen University Cancer Center  Guangzhou P. 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