{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:38:07Z","timestamp":1788482287232,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2018,11,5]],"date-time":"2018-11-05T00:00:00Z","timestamp":1541376000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000871","name":"Mayo Clinic","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008308","name":"Comprehensive Cancer Center, City of Hope","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008308","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Axitinib is an oral small molecule that inhibits receptor tyrosine kinases vascular endothelial growth factor receptors 1 to 3. A phase 1 and pharmacokinetic (PK) trial evaluating axitinib was conducted in children with refractory solid tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Axitinib was administered orally twice daily in continuous 28\u2010day cycles. Dose levels (2.4 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      \/dose and 3.2 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      \/dose) were evaluated using a rolling 6 design. Serial PKs (cycle 1, days 1 and 8) and exploratory biomarkers were analyzed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 19 patients were enrolled; 1 patient was ineligible due to inadequate time having elapsed from prior therapy. The median age of the patients was 13.5 years (range, 5\u201017 years). Two of 5 patients who were treated at dose level 2 experienced dose\u2010limiting toxicities (palmar\u2010plantar erythryodysesthesia syndrome in 1 patient and intratumoral hemorrhage in 1 patient). Frequent (&gt;20%) grade 1 to 2 toxicities during cycle 1 included anemia, anorexia, fatigue, diarrhea, nausea, and hypertension. Nonhematological toxicities of grade \u22653 in subsequent cycles included hypertension and elevated serum lipase. PK analysis demonstrated variability in axitinib exposure, the median time to peak plasma concentration was 2 hours, and the half\u2010life ranged from 0.7 to 5.2 hours. Exposure and dose were not found to be significantly associated with hypertension. Five patients achieved stable disease for \u22656 cycles as their best response, including patients with malignant peripheral nerve sheath tumor (1 patient), Ewing sarcoma (1 patient), hepatocellular carcinoma (1 patient), and osteosarcoma (2 patients). One patient with alveolar soft part sarcoma achieved a partial response. Kidney injury biomarkers were found to be elevated at baseline; no trends were identified.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In children with refractory solid tumors, the maximum tolerated and recommended dose of axitinib appears to be 2.4 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      \/dose, which provides PK exposures similar to those of adults.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.31725","type":"journal-article","created":{"date-parts":[[2018,11,5]],"date-time":"2018-11-05T06:39:09Z","timestamp":1541399949000},"page":"4548-4555","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["A study of axitinib, a VEGF receptor tyrosine kinase inhibitor, in children and adolescents with recurrent or refractory solid tumors: A Children\u2019s Oncology Group phase 1 and pilot consortium trial (ADVL1315)"],"prefix":"10.1002","volume":"124","author":[{"given":"James I.","family":"Geller","sequence":"first","affiliation":[{"name":"Cancer and Blood Diseases Institute, Cincinnati Children\u2019s Hospital Medical Center University of Cincinnati Cincinnati Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Fox","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Children\u2019s Hospital of Philadelphia Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian K.","family":"Turpin","sequence":"additional","affiliation":[{"name":"Cancer and Blood Diseases Institute, Cincinnati Children\u2019s Hospital Medical Center University of Cincinnati Cincinnati Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart 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