{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:50:11Z","timestamp":1791474611985,"version":"4.3.4"},"reference-count":24,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"26","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2006,9,10]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> This phase II study of sorafenib, an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases, assessed efficacy, toxicity, pharmacokinetics, and biomarkers in advanced hepatocellular carcinoma (HCC) patients. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p> Patients with inoperable HCC, no prior systemic treatment, and Child\u2013Pugh (CP) A or B, received continuous, oral sorafenib 400 mg bid in 4-week cycles. Tumor response was assessed every two cycles using modified WHO criteria. Sorafenib pharmacokinetics were measured in plasma samples. Biomarker analysis included phosphorylated extracellular signal regulated kinase (pERK) in pretreatment biopsies (immunohistochemistry) and blood-cell RNA expression patterns in selected patients. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Of 137 patients treated (male, 71%; median age, 69 years), 72% had CP A, and 28% had CP B. On the basis of independent assessment, three (2.2%) patients achieved a partial response, eight (5.8%) had a minor response, and 46 (33.6%) had stable disease for at least 16 weeks. Investigator-assessed median time to progression (TTP) was 4.2 months, and median overall survival was 9.2 months. Grade 3\/4 drug-related toxicities included fatigue (9.5%), diarrhea (8.0%), and hand\u2013foot skin reaction (5.1%). There were no significant pharmacokinetic differences between CP A and B patients. Pretreatment tumor pERK levels correlated with TTP. A panel of 18 expressed genes was identified that distinguished \u201cnonprogressors\u201d from \u201cprogressors\u201d with an estimated 100% accuracy. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Although single-agent sorafenib has modest efficacy in HCC, the manageable toxicity and mechanisms of action support a role for combination regimens with other anticancer agents. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2005.01.3441","type":"journal-article","created":{"date-parts":[[2006,8,15]],"date-time":"2006-08-15T00:40:10Z","timestamp":1155602410000},"page":"4293-4300","source":"Crossref","is-referenced-by-count":959,"title":["Phase II Study of Sorafenib in Patients With Advanced Hepatocellular Carcinoma"],"prefix":"10.1200","volume":"24","author":[{"given":"Ghassan K.","family":"Abou-Alfa","sequence":"first","affiliation":[{"name":"From the Memorial Sloan-Kettering Cancer Center, New York, NY; Bayer Pharmaceuticals Corporation, West Haven, CT; Ospedale S. Chiara, Pisa; Ospedale Morgagni Pierantoni, Forli; Istituto Clinico Humanitas, Rozzano (MI); Bayer S.p.A. PH\/Medical Department, Milan, Italy; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; AZ-VUB, Brussels, Belgium; and the Centre Ren\u00e9 Gauducheau, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Schwartz","sequence":"additional","affiliation":[{"name":"From the Memorial Sloan-Kettering Cancer Center, New York, NY; Bayer Pharmaceuticals Corporation, West Haven, CT; Ospedale S. Chiara, Pisa; Ospedale Morgagni Pierantoni, Forli; Istituto Clinico Humanitas, Rozzano (MI); Bayer S.p.A. PH\/Medical Department, Milan, Italy; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; AZ-VUB, Brussels, Belgium; and the Centre Ren\u00e9 Gauducheau, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Ricci","sequence":"additional","affiliation":[{"name":"From the Memorial Sloan-Kettering Cancer Center, New York, NY; Bayer Pharmaceuticals Corporation, West Haven, CT; Ospedale S. Chiara, Pisa; Ospedale Morgagni Pierantoni, Forli; Istituto Clinico Humanitas, Rozzano (MI); Bayer S.p.A. PH\/Medical Department, Milan, Italy; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; AZ-VUB, Brussels, Belgium; and the Centre Ren\u00e9 Gauducheau, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dino","family":"Amadori","sequence":"additional","affiliation":[{"name":"From the Memorial Sloan-Kettering Cancer Center, New York, NY; Bayer Pharmaceuticals Corporation, West Haven, CT; Ospedale S. Chiara, Pisa; Ospedale Morgagni Pierantoni, Forli; Istituto Clinico Humanitas, Rozzano (MI); Bayer S.p.A. PH\/Medical Department, Milan, Italy; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; AZ-VUB, Brussels, Belgium; and the Centre Ren\u00e9 Gauducheau, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando","family":"Santoro","sequence":"additional","affiliation":[{"name":"From the Memorial Sloan-Kettering Cancer Center, New York, NY; Bayer Pharmaceuticals Corporation, West Haven, CT; Ospedale S. Chiara, Pisa; Ospedale Morgagni Pierantoni, Forli; Istituto Clinico Humanitas, Rozzano (MI); Bayer S.p.A. PH\/Medical Department, Milan, Italy; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; AZ-VUB, Brussels, Belgium; and the Centre Ren\u00e9 Gauducheau, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arie","family":"Figer","sequence":"additional","affiliation":[{"name":"From the Memorial Sloan-Kettering Cancer Center, New York, NY; Bayer Pharmaceuticals Corporation, West Haven, CT; Ospedale S. Chiara, Pisa; Ospedale Morgagni Pierantoni, Forli; Istituto Clinico Humanitas, Rozzano (MI); Bayer S.p.A. PH\/Medical Department, Milan, Italy; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; AZ-VUB, Brussels, Belgium; and the Centre Ren\u00e9 Gauducheau, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"De Greve","sequence":"additional","affiliation":[{"name":"From the Memorial Sloan-Kettering Cancer Center, New York, NY; Bayer Pharmaceuticals Corporation, West Haven, CT; Ospedale S. Chiara, Pisa; Ospedale Morgagni Pierantoni, Forli; Istituto Clinico Humanitas, Rozzano (MI); Bayer S.p.A. PH\/Medical Department, Milan, Italy; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; AZ-VUB, Brussels, Belgium; and the Centre Ren\u00e9 Gauducheau, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Yves","family":"Douillard","sequence":"additional","affiliation":[{"name":"From the Memorial Sloan-Kettering Cancer Center, New York, NY; Bayer Pharmaceuticals Corporation, West Haven, CT; Ospedale S. Chiara, Pisa; Ospedale Morgagni Pierantoni, Forli; Istituto Clinico Humanitas, Rozzano (MI); Bayer S.p.A. PH\/Medical Department, Milan, Italy; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; AZ-VUB, Brussels, Belgium; and the Centre Ren\u00e9 Gauducheau, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chetan","family":"Lathia","sequence":"additional","affiliation":[{"name":"From the Memorial Sloan-Kettering Cancer Center, New York, NY; Bayer Pharmaceuticals Corporation, West Haven, CT; Ospedale S. Chiara, Pisa; Ospedale Morgagni Pierantoni, Forli; Istituto Clinico Humanitas, Rozzano (MI); Bayer S.p.A. PH\/Medical Department, Milan, Italy; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; AZ-VUB, Brussels, Belgium; and the Centre Ren\u00e9 Gauducheau, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Schwartz","sequence":"additional","affiliation":[{"name":"From the Memorial Sloan-Kettering Cancer Center, New York, NY; Bayer Pharmaceuticals Corporation, West Haven, CT; Ospedale S. Chiara, Pisa; Ospedale Morgagni Pierantoni, Forli; Istituto Clinico Humanitas, Rozzano (MI); Bayer S.p.A. PH\/Medical Department, Milan, Italy; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; AZ-VUB, Brussels, Belgium; and the Centre Ren\u00e9 Gauducheau, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Taylor","sequence":"additional","affiliation":[{"name":"From the Memorial Sloan-Kettering Cancer Center, New York, NY; Bayer Pharmaceuticals Corporation, West Haven, CT; Ospedale S. Chiara, Pisa; Ospedale Morgagni Pierantoni, Forli; Istituto Clinico Humanitas, Rozzano (MI); Bayer S.p.A. PH\/Medical Department, Milan, Italy; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; AZ-VUB, Brussels, Belgium; and the Centre Ren\u00e9 Gauducheau, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Moscovici","sequence":"additional","affiliation":[{"name":"From the Memorial Sloan-Kettering Cancer Center, New York, NY; Bayer Pharmaceuticals Corporation, West Haven, CT; Ospedale S. Chiara, Pisa; Ospedale Morgagni Pierantoni, Forli; Istituto Clinico Humanitas, Rozzano (MI); Bayer S.p.A. PH\/Medical Department, Milan, Italy; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; AZ-VUB, Brussels, Belgium; and the Centre Ren\u00e9 Gauducheau, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard B.","family":"Saltz","sequence":"additional","affiliation":[{"name":"From the Memorial Sloan-Kettering Cancer Center, New York, NY; Bayer Pharmaceuticals Corporation, West Haven, CT; Ospedale S. Chiara, Pisa; Ospedale Morgagni Pierantoni, Forli; Istituto Clinico Humanitas, Rozzano (MI); Bayer S.p.A. PH\/Medical Department, Milan, Italy; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; AZ-VUB, Brussels, Belgium; and the Centre Ren\u00e9 Gauducheau, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19990315)80:6<827::AID-IJC6>3.0.CO;2-P"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.1456"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199903113401001"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1053\/he.2000.6959"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1186\/1471-230X-3-19"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204372"},{"key":"R8","doi-asserted-by":"crossref","unstructured":"Shimotohno K, Watashi K, Tsuchihara K, et al: Hepatitis C virus and its roles in cell proliferation. J Gastroenterol 37:50,2002-54,  (suppl)","DOI":"10.1007\/BF02990100"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20218"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-1443"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.06.124"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.2307\/2344317"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)07678-X"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-0243"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(05)80243-0"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.49.6.470"},{"key":"R17","unstructured":"DeVita VT Jr, Abou-Alfa GK: Therapeutic implications of the new biology. Cancer J 6: Suppl 2:S113,2000\u2013S120,"},{"key":"R18","unstructured":"Jiang W, Lu Z, He Y, et al: Dihydropyrimidine dehydrogenase activity in hepatocellular carcinoma: Implication in 5-fluorouracil-based chemotherapy. Clin Cancer Res 3:395,1997-399,"},{"key":"R20","unstructured":"Leung TW, Patt YZ, Lau WY, et al: Complete pathological remission is possible with systemic combination chemotherapy for inoperable hepatocellular carcinoma. Clin Cancer Res 5:1676,1999-1681,"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-004-0837-7"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dji315"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.5414\/CPP42650"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-3-3"},{"key":"R25","doi-asserted-by":"crossref","unstructured":"Qin LX, Tang ZY: Recent progress in predictive biomarkers for metastatic recurrence of human hepatocellular carcinoma: A review of the literature. J Cancer Res Clin Oncol 130:497,2004-513,","DOI":"10.1007\/s00432-004-0572-9"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81189-7"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2005.01.3441","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T21:22:10Z","timestamp":1653513730000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2005.01.3441"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,9,10]]},"references-count":24,"journal-issue":{"issue":"26","published-print":{"date-parts":[[2006,9,10]]}},"alternative-id":["10.1200\/JCO.2005.01.3441"],"URL":"https:\/\/doi.org\/10.1200\/jco.2005.01.3441","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,9,10]]}}}