{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T21:39:30Z","timestamp":1782509970198,"version":"3.54.5"},"reference-count":29,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,8,15]],"date-time":"2020-08-15T00:00:00Z","timestamp":1597449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Preclinical observations suggested a synergistic effect of sorafenib (SFN) and irinotecan (CPT\u201011) in hepatoblastoma (HB). Thus, we conducted a feasibility study of fractionated CPT\u201011 combined with SFN to develop a new therapy against relapsed\/refractory pediatric hepatic cancer (HC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>The study was originally designed as a phase I, standard 3+3 dose\u2010finding study to evaluate dose\u2010limiting toxicities (DLTs) for the regimen and the optimal CPT\u201011 dose in combination with SFN against relapsed\/refractory pediatric HC, including HB and hepatocellular carcinoma (HCC). The enrolled patients received SFN at 200\u00a0mg\/m<jats:sup>2<\/jats:sup> every 12\u00a0hours or 400\u00a0mg\/m<jats:sup>2<\/jats:sup> every 24\u00a0hours daily combined with CPT\u201011 at 20\u00a0mg\/m<jats:sup>2<\/jats:sup>\/day on days 1 to 5 as an initial level 1 dose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Six patients with HB (<jats:italic>n<\/jats:italic>\u00a0=\u00a04) or HCC (<jats:italic>n<\/jats:italic>\u00a0=\u00a02) were enrolled and treated with CPT\u201011 dose level 1. The median age at enrollment was 8.7 (6.2\u201016.3) years. All patients received platinum\u2010containing chemotherapy, and five or two patients received CPT\u201011 or SFN before enrollment, respectively. Regimen toxicities were evaluable in all patients. One of six patients experienced a grade 4 transaminase levels increase, which was defined as a DLT per protocol. Grade 3\/4 neutropenia and a grade 3 transaminase level increase occurred in three patients and one patient, respectively. All patients reported grade 1\/2 toxicities such as anemia, skin toxicity, gastrointestinal symptoms, and hypoalbuminemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Although the study was terminated before determining the maximum\u2010tolerated CPT\u201011 dose, SFN and CPT\u201011 at the level 1 dose were concluded to be tolerable in pediatric patients with HC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.28655","type":"journal-article","created":{"date-parts":[[2020,8,15]],"date-time":"2020-08-15T08:30:40Z","timestamp":1597480240000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Pilot study of the combination of sorafenib and fractionated irinotecan in pediatric relapse\/refractory hepatic cancer (FINEX pilot 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