{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T07:19:26Z","timestamp":1792739966603,"version":"4.5.0"},"reference-count":19,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"22","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2008,8,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To assess the safety and efficacy of sunitinib in patients with bevacizumab-refractory metastatic renal cell carcinoma (mRCC) and explore biomarkers for sunitinib response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>Patients with mRCC and disease progression after bevacizumab-based therapy received oral sunitinib 50 mg once daily in 6-week cycles on a 4\/2 schedule (4 weeks with treatment followed by 2 weeks without treatment) in a phase II multicenter study. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), duration of response (DR), overall survival (OS), and safety. Plasma soluble proteins (vascular endothelial growth factor [VEGF]-A, VEGF-C, soluble VEGF receptor [sVEGFR]-3, and placental growth factor [PlGF]) levels were measured.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Sixty-one patients were enrolled. The ORR was 23.0% (95% CI, 13.2% to 35.5%), median PFS was 30.4 weeks (95% CI, 18.3 to 36.7 weeks), median DR was 44.1 weeks (95% CI, 25.0 to 102.7 weeks), and median OS was 47.1 weeks (95% CI, 36.9 to 79.4 weeks). Mean plasma VEGF-A and PlGF levels significantly increased whereas VEGF-C and sVEGFR-3 levels decreased with sunitinib treatment. Lower baseline levels of sVEGFR-3 and VEGF-C were associated with longer PFS and ORR. Most treatment-related adverse events were of mild-to-moderate intensity and included fatigue, hypertension, and hand-foot syndrome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Sunitinib has substantial antitumor activity in patients with bevacizumab-refractory mRCC and modulates circulating VEGF pathway biomarkers. These data support the hypothesis that sunitinib inhibits signaling pathways involved in bevacizumab resistance. Baseline levels of sVEGFR-3 and VEGF-C may have potential utility as biomarkers of clinical efficacy in this setting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.2007.15.5416","type":"journal-article","created":{"date-parts":[[2008,7,30]],"date-time":"2008-07-30T21:07:13Z","timestamp":1217452033000},"page":"3743-3748","source":"Crossref","is-referenced-by-count":334,"title":["Antitumor Activity and Biomarker Analysis of Sunitinib in Patients With Bevacizumab-Refractory Metastatic Renal Cell Carcinoma"],"prefix":"10.1200","volume":"26","author":[{"given":"Brian I.","family":"Rini","sequence":"first","affiliation":[{"name":"From the Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Massachusetts General Hospital, Boston, MA; University of California, San Francisco; City of Hope, Los Angeles; Pfizer Global Research and Development, La Jolla, CA; Vanderbilt University, Nashville, TN; University of Chicago, Chicago, IL; Baylor-Sammons\/Texas Oncology, Dallas, TX; and Duke University Medical Center, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Dror","family":"Michaelson","sequence":"additional","affiliation":[{"name":"From the Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Massachusetts General Hospital, Boston, MA; University of California, San Francisco; City of Hope, Los Angeles; Pfizer Global Research and Development, La Jolla, CA; Vanderbilt University, Nashville, TN; University of Chicago, Chicago, IL; Baylor-Sammons\/Texas Oncology, Dallas, TX; and Duke University Medical Center, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan E.","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"From the Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Massachusetts General Hospital, Boston, MA; University of California, San Francisco; City of Hope, Los Angeles; Pfizer Global Research and Development, La Jolla, CA; Vanderbilt University, Nashville, TN; University of Chicago, Chicago, IL; Baylor-Sammons\/Texas Oncology, Dallas, TX; and Duke University Medical Center, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald M.","family":"Bukowski","sequence":"additional","affiliation":[{"name":"From the Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Massachusetts General Hospital, Boston, MA; University of California, San Francisco; City of Hope, Los Angeles; Pfizer Global Research and Development, La Jolla, CA; Vanderbilt University, Nashville, TN; University of Chicago, Chicago, IL; Baylor-Sammons\/Texas Oncology, Dallas, TX; and Duke University Medical Center, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Sosman","sequence":"additional","affiliation":[{"name":"From the Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Massachusetts General Hospital, Boston, MA; University of California, San Francisco; City of Hope, Los Angeles; Pfizer Global Research and Development, La Jolla, CA; Vanderbilt University, Nashville, TN; University of Chicago, Chicago, IL; Baylor-Sammons\/Texas Oncology, Dallas, TX; and Duke University Medical Center, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter M.","family":"Stadler","sequence":"additional","affiliation":[{"name":"From the Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Massachusetts General Hospital, Boston, MA; University of California, San Francisco; City of Hope, Los Angeles; Pfizer Global Research and Development, La Jolla, CA; Vanderbilt University, Nashville, TN; University of Chicago, Chicago, IL; Baylor-Sammons\/Texas Oncology, Dallas, TX; and Duke University Medical Center, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Hutson","sequence":"additional","affiliation":[{"name":"From the Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Massachusetts General Hospital, Boston, MA; University of California, San Francisco; City of Hope, Los Angeles; Pfizer Global Research and Development, La Jolla, CA; Vanderbilt University, Nashville, TN; University of Chicago, Chicago, IL; Baylor-Sammons\/Texas Oncology, Dallas, TX; and Duke University Medical Center, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Margolin","sequence":"additional","affiliation":[{"name":"From the Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Massachusetts General Hospital, Boston, MA; University of California, San Francisco; City of Hope, Los Angeles; Pfizer Global Research and Development, La Jolla, CA; Vanderbilt University, Nashville, TN; University of Chicago, Chicago, IL; Baylor-Sammons\/Texas Oncology, Dallas, TX; and Duke University Medical Center, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles S.","family":"Harmon","sequence":"additional","affiliation":[{"name":"From the Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Massachusetts General Hospital, Boston, MA; University of California, San Francisco; City of Hope, Los Angeles; Pfizer Global Research and Development, La Jolla, CA; Vanderbilt University, Nashville, TN; University of Chicago, Chicago, IL; Baylor-Sammons\/Texas Oncology, Dallas, TX; and Duke University Medical Center, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel E.","family":"DePrimo","sequence":"additional","affiliation":[{"name":"From the Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Massachusetts General Hospital, Boston, MA; University of California, San Francisco; City of Hope, Los Angeles; Pfizer Global Research and Development, La Jolla, CA; Vanderbilt University, Nashville, TN; University of Chicago, Chicago, IL; Baylor-Sammons\/Texas Oncology, Dallas, TX; and Duke University Medical Center, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sindy T.","family":"Kim","sequence":"additional","affiliation":[{"name":"From the Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Massachusetts General Hospital, Boston, MA; University of California, San Francisco; City of Hope, Los Angeles; Pfizer Global Research and Development, La Jolla, CA; Vanderbilt University, Nashville, TN; University of Chicago, Chicago, IL; Baylor-Sammons\/Texas Oncology, Dallas, TX; and Duke University Medical Center, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isan","family":"Chen","sequence":"additional","affiliation":[{"name":"From the Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Massachusetts General Hospital, Boston, MA; University of California, San Francisco; City of Hope, Los Angeles; Pfizer Global Research and Development, La Jolla, CA; Vanderbilt University, Nashville, TN; University of Chicago, Chicago, IL; Baylor-Sammons\/Texas Oncology, Dallas, TX; and Duke University Medical Center, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"George","sequence":"additional","affiliation":[{"name":"From the Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Massachusetts General Hospital, Boston, MA; University of California, San Francisco; City of Hope, Los Angeles; Pfizer Global Research and Development, La Jolla, CA; Vanderbilt University, Nashville, TN; University of Chicago, Chicago, IL; Baylor-Sammons\/Texas Oncology, Dallas, TX; and Duke University Medical Center, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.01.186"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.06.3602"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa065044"},{"key":"R4","doi-asserted-by":"crossref","unstructured":"Escudier B, Koralewski P, Pluzanska A, et al: A randomized, controlled, double-blind phase III study (AVOREN) of bevacizumab\/interferon-\u03b12a vs placebo\/interferon-\u03b12a as first-line therapy in metastatic renal cell carcinoma. J Clin Oncol 25:2s,2007,  (suppl; abstr 3)","DOI":"10.1200\/jco.2007.25.18_suppl.3"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.3.205"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-003-0776-3"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2005.11.012"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6603120"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.08.5415"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-5-32"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.06.132"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1001\/jama.295.21.2516"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.06.1143"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.08.8245"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.02.5635"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020778001267"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-0847"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-03-0627"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.12.8637"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2007.15.5416","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T16:17:28Z","timestamp":1653495448000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2007.15.5416"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,8,1]]},"references-count":19,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2008,8,1]]}},"alternative-id":["10.1200\/JCO.2007.15.5416"],"URL":"https:\/\/doi.org\/10.1200\/jco.2007.15.5416","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1122822.579910","asserted-by":"object"}]},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,8,1]]}}}