{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T12:48:36Z","timestamp":1767703716272,"version":"3.40.5"},"reference-count":20,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,6,14]],"date-time":"2019-06-14T00:00:00Z","timestamp":1560470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004326","name":"Bayer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:p>Regorafenib 160\u2009mg orally once daily (QD) 3 weeks on\/1 week off is approved in colorectal cancer, gastrointestinal stromal tumors and hepatocellular carcinoma. We established the safety and pharmacokinetics (PK) of regorafenib combined with cetuximab in advanced refractory solid tumors. This was a phase 1, open\u2010label, dose\u2010escalation study (NCT01973868) in patients with advanced\/metastatic solid tumors who progressed after standard therapy. Regorafenib was administered at various dose levels QD continuously or intermittently (3\u2009weeks on\/1\u2009week off) combined with intravenous cetuximab 250\u2009mg\/m<jats:sup>2<\/jats:sup> weekly. The primary objectives were safety, PK and maximum tolerated dose (MTD). The secondary objective was tumor response. Dose\u2010limiting toxicities (DLTs) were evaluated in Cycle 1. Of 42 treated patients, 31 received regorafenib intermittently (120\u2009mg, <jats:italic>n<\/jats:italic>\u2009=\u20098; 160\u2009mg, <jats:italic>n<\/jats:italic>\u2009=\u200923) and 11 continuously (60\u2009mg, <jats:italic>n<\/jats:italic>\u2009=\u20095; 100\u2009mg, <jats:italic>n<\/jats:italic>\u2009=\u20096) plus cetuximab. The continuous arm was terminated due to low tolerable dose. In the intermittent arm, one DLT (grade 3 hand\u2013foot skin reaction) was observed at 120\u2009mg but none at 160\u2009mg, therefore 160\u2009mg\/day was declared as the MTD in combination with cetuximab. The most common all\u2010grade treatment\u2010emergent adverse events were fatigue (52%), hypophosphatemia (48%) and diarrhea (40%). One grade 3 cetuximab\u2010related dermatitis acneiform was observed. No clinically relevant drug\u2013drug interactions were observed. Five patients (21%) had a partial response. Regorafenib 160\u2009mg QD (3 weeks on\/1 week off) plus standard dose of cetuximab was well tolerated with no unexpected toxicities and promising signs of efficacy.<\/jats:p>","DOI":"10.1002\/ijc.32317","type":"journal-article","created":{"date-parts":[[2019,4,8]],"date-time":"2019-04-08T16:40:28Z","timestamp":1554741628000},"page":"2450-2458","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A phase 1b study evaluating the safety and pharmacokinetics of regorafenib in combination with cetuximab in patients with advanced solid tumors"],"prefix":"10.1002","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6287-4334","authenticated-orcid":false,"given":"Colin","family":"Weekes","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology Massachusetts General Hospital  Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. 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