{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:13:37Z","timestamp":1791087217475,"version":"4.1.0"},"reference-count":33,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2009,4,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Based on the pivotal role of Ras-Raf-MAP-ERK signaling and vascular endothelial growth factor (VEGF) in papillary thyroid cancer (PTC), we conducted a phase II clinical trial of sorafenib targeting RAF and VEGF receptor kinases in PTC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>The primary end point was the objective response rate. Secondary end points included response correlation with serum thyroglobulin (Tg); functional imaging; tumor genotype; and signaling inhibition in tumor biopsies. Using a Simon minimax two-stage design, 16 or 25 chemotherapy-na\u00efve metastatic PTC patients were to be enrolled in arm A (accessible tumor for biopsy). Arm B patients had other subtypes of thyroid carcinoma or prior chemotherapy, and did not require tumor biopsies. Patients received 400 mg orally twice per day of sorafenib. Response was assessed every 2 months using RECIST (Response Evaluation Criteria in Solid Tumors).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 41 PTC patients, six patients had a partial response (PR; 15%; 95% CI, 6 to 29) and 23 patients (56%; 95% CI, 40 to 72) had stable disease longer than 6 months. Median duration of PR was 7.5 months (range, 6 to 14). Median progression-free survival was 15 months (95% CI, 10 to 27.5). In 14 (78%) of 18 Tg-assessable PTC patients, Tg declined more than 25%. Common grade 3 adverse events included hand-foot skin reaction, musculoskeletal pain, and fatigue. BRAF mutation was detected in 17 (77%) of 22 PTCs analyzed. Four of 10 paired tumor biopsies from PTC patients showed a reduction in levels of vascular endothelial growth factor receptor phosphorylation, ERK phosphorylation, and in VEGF expression during sorafenib therapy. No PRs were noted among non-PTC patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Sorafenib is reasonably well-tolerated therapy with clinical and biologic antitumor activity in metastatic PTC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.2008.18.2717","type":"journal-article","created":{"date-parts":[[2009,3,2]],"date-time":"2009-03-02T21:11:18Z","timestamp":1236028278000},"page":"1675-1684","source":"Crossref","is-referenced-by-count":438,"title":["Phase II Trial of Sorafenib in Metastatic Thyroid Cancer"],"prefix":"10.1200","volume":"27","author":[{"given":"Richard T.","family":"Kloos","sequence":"first","affiliation":[{"name":"From the Ohio State University, Departments of Internal Medicine, Molecular Virology, Immunology, and Genetics, Pathology, Radiology, Center for Biostatistics, Ohio State University, Columbus, OH; Center for Therapy and Evaluation Program, National Cancer Institute; and Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"Ringel","sequence":"additional","affiliation":[{"name":"From the Ohio State University, Departments of Internal Medicine, Molecular Virology, Immunology, and Genetics, Pathology, Radiology, Center for Biostatistics, Ohio State University, Columbus, OH; Center for Therapy and Evaluation Program, National Cancer Institute; and Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael V.","family":"Knopp","sequence":"additional","affiliation":[{"name":"From the Ohio State University, Departments of Internal Medicine, Molecular Virology, Immunology, and Genetics, Pathology, Radiology, Center for Biostatistics, Ohio State University, Columbus, OH; Center for Therapy and Evaluation Program, National Cancer Institute; and Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan C.","family":"Hall","sequence":"additional","affiliation":[{"name":"From the Ohio State University, Departments of Internal Medicine, Molecular Virology, Immunology, and Genetics, Pathology, Radiology, Center for Biostatistics, Ohio State University, Columbus, OH; Center for Therapy and Evaluation Program, National Cancer Institute; and Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"King","sequence":"additional","affiliation":[{"name":"From the Ohio State University, Departments of Internal Medicine, Molecular Virology, Immunology, and Genetics, Pathology, Radiology, Center for Biostatistics, Ohio State University, Columbus, OH; Center for Therapy and Evaluation Program, National Cancer Institute; and Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Stevens","sequence":"additional","affiliation":[{"name":"From the Ohio State University, Departments of Internal Medicine, Molecular Virology, Immunology, and Genetics, Pathology, Radiology, Center for Biostatistics, Ohio State University, Columbus, OH; Center for Therapy and Evaluation Program, National Cancer Institute; and Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiachao","family":"Liang","sequence":"additional","affiliation":[{"name":"From the Ohio State University, Departments of Internal Medicine, Molecular Virology, Immunology, and Genetics, Pathology, Radiology, Center for Biostatistics, Ohio State University, Columbus, OH; Center for Therapy and Evaluation Program, National Cancer Institute; and Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Paul E.","family":"Wakely","sequence":"additional","affiliation":[{"name":"From the Ohio State University, Departments of Internal Medicine, Molecular Virology, Immunology, and Genetics, Pathology, Radiology, Center for Biostatistics, Ohio State University, Columbus, OH; Center for Therapy and Evaluation Program, National Cancer Institute; and Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasyl V.","family":"Vasko","sequence":"additional","affiliation":[{"name":"From the Ohio State University, Departments of Internal Medicine, Molecular Virology, Immunology, and Genetics, Pathology, Radiology, Center for Biostatistics, Ohio State University, Columbus, OH; Center for Therapy and Evaluation Program, National Cancer Institute; and Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoyasu","family":"Saji","sequence":"additional","affiliation":[{"name":"From the Ohio State University, Departments of Internal Medicine, Molecular Virology, Immunology, and Genetics, Pathology, Radiology, Center for Biostatistics, Ohio State University, Columbus, OH; Center for Therapy and Evaluation Program, National Cancer Institute; and Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Rittenberry","sequence":"additional","affiliation":[{"name":"From the Ohio State University, Departments of Internal Medicine, Molecular Virology, Immunology, and Genetics, Pathology, Radiology, Center for Biostatistics, Ohio State University, Columbus, OH; Center for Therapy and Evaluation Program, National Cancer Institute; and Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lai","family":"Wei","sequence":"additional","affiliation":[{"name":"From the Ohio State University, Departments of Internal Medicine, Molecular Virology, Immunology, and Genetics, Pathology, Radiology, Center for Biostatistics, Ohio State University, Columbus, OH; Center for Therapy and Evaluation Program, National Cancer Institute; and Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Arbogast","sequence":"additional","affiliation":[{"name":"From the Ohio State University, Departments of Internal Medicine, Molecular Virology, Immunology, and Genetics, Pathology, Radiology, Center for Biostatistics, Ohio State University, Columbus, OH; Center for Therapy and Evaluation Program, National Cancer Institute; and Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minden","family":"Collamore","sequence":"additional","affiliation":[{"name":"From the Ohio State University, Departments of Internal Medicine, Molecular Virology, Immunology, and Genetics, Pathology, Radiology, Center for Biostatistics, Ohio State University, Columbus, OH; Center for Therapy and Evaluation Program, National Cancer Institute; and Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Wright","sequence":"additional","affiliation":[{"name":"From the Ohio State University, Departments of Internal Medicine, Molecular Virology, Immunology, and Genetics, Pathology, Radiology, Center for Biostatistics, Ohio State University, Columbus, OH; Center for Therapy and Evaluation Program, National Cancer Institute; 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