{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T18:16:36Z","timestamp":1778609796811,"version":"3.51.4"},"reference-count":17,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2010,11,29]],"date-time":"2010-11-29T00:00:00Z","timestamp":1290988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND:<\/jats:title><jats:p>Bevacizumab and sunitinib are standard initial therapy in metastatic renal cell carcinoma (mRCC). Despite common use, the safety and activity of sorafenib in bevacizumab\u2010 or sunitinib\u2010refractory mRCC have not been prospectively investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>Metastatic RCC patients with Response Evaluation Criteria in Solid Tumors (RECIST)\u2010defined disease progression (PD) after treatment with either bevacizumab or sunitinib received twice daily 400 mg of sorafenib in a multicenter, prospective phase 2 study. Dose escalation was permitted in the absence of significant toxicity. The primary endpoint was tumor burden reduction rate, defined as the proportion of patients with \u22655% reduction in the sum of RECIST\u2010defined target lesions without other PD. Secondary endpoints included progression\u2010free survival (PFS), duration of response, overall survival, and safety. A 2\u2010stage accrual design was used to test the alternative hypothesis that the tumor burden reduction rate was &gt;20% versus &lt;5%.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>Forty\u2010eight patients were enrolled. The tumor burden reduction rate was 30% (95% confidence interval [CI], 17%\u201045%). One unconfirmed objective partial response was observed. The median PFS was 4.4 months (95% CI, 3.6\u20105.9). There was no association of PFS and tumor shrinkage with response to prior therapy. Most treatment\u2010related adverse events were of mild\u2010to\u2010moderate intensity, and included fatigue, hypertension, diarrhea, and palmoplantar erythrodysesthesia (PPE). Patients previously treated with bevacizumab tended to develop more PPE (<jats:italic>P<\/jats:italic> = .03) and mucositis (<jats:italic>P<\/jats:italic> = .06), whereas sunitinib\u2010treated patients tended to develop more skin rash (<jats:italic>P<\/jats:italic> = .06).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS:<\/jats:title><jats:p>Administration of sorafenib is safe and feasible in patients with mRCC refractory to either bevacizumab or sunitinib. Modest clinical activity was observed supporting current practice patterns of sequential vascular endothelial growth factor\u2010targeted therapy in mRCC. Cancer 2010. \u00a9 2010 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.25327","type":"journal-article","created":{"date-parts":[[2010,8,31]],"date-time":"2010-08-31T11:55:38Z","timestamp":1283255738000},"page":"5383-5390","source":"Crossref","is-referenced-by-count":54,"title":["Sorafenib in patients with metastatic renal cell carcinoma refractory to either sunitinib or bevacizumab"],"prefix":"10.1002","volume":"116","author":[{"given":"Jorge A.","family":"Garcia","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas E.","family":"Hutson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Elson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. Lance","family":"Cowey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Gilligan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheryl","family":"Nemec","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Dreicer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald M.","family":"Bukowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian I.","family":"Rini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,11,29]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa065044"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61904-7"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.9847"},{"issue":"15","key":"e_1_2_6_5_2","article-title":"A randomized, double\u2010blind phase III study of pazopanib in treatment\u2010naive and cytokine\u2010pretreated patients with advanced renal cell carcinoma (RCC) [abstract]","volume":"27","author":"Stenberg CN","year":"2009","journal-title":"J Clin Oncol."},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61039-9"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2007.08.127"},{"issue":"18","key":"e_1_2_6_8_2","article-title":"Sequential use of sorafenib and sunitinib in renal cancer: retrospective analysis in 90 patients [abstract]","volume":"25","author":"Sablin MP","year":"2007","journal-title":"J Clin Oncol."},{"issue":"18","key":"e_1_2_6_9_2","article-title":"Evaluation of VEGF targeted therapy efficacy in mRCC after sorafenib failure or intolerance [abstract]","volume":"25","author":"Hajdenberg J","year":"2007","journal-title":"J Clin Oncol."},{"key":"e_1_2_6_10_2","first-page":"A78","article-title":"BAY 43\u20109006 exhibits broad spectrum anti\u2010tumor activity and targets raf\/MEK\/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis [abstract]","volume":"44","author":"Wilhelm S","year":"2003","journal-title":"Proc Am Assoc Cancer Res."},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.03.6723"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa060655"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.19.3342"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.3.205"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22827"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.22.6480"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.5416"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.21.7034"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.25327","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.25327","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T09:33:58Z","timestamp":1760261638000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.25327"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,11,29]]},"references-count":17,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2010,12]]}},"alternative-id":["10.1002\/cncr.25327"],"URL":"https:\/\/doi.org\/10.1002\/cncr.25327","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,11,29]]}}}