{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:11:42Z","timestamp":1787238702156,"version":"build-2736575974"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2019,5,31]],"date-time":"2019-05-31T00:00:00Z","timestamp":1559260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Lessons Learned<\/jats:title>\n                    <jats:p>The negative results are consistent with the negative results of large phase III trials in which docetaxel plus antiangiogenic agents were used in patients with metastatic castrate-resistant prostate cancer (mCRPC). The negative data underscore that, despite a sound biological rationale and supportive early-phase clinical results, adding antiangiogenic agents to docetaxel for mCRPC is a great challenge.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Inhibition of vascular endothelial growth factor (VEGF) signaling abrogates tumor-induced angiogenesis to constrain tumor growth, and can be exploited therapeutically by using cediranib, an oral tyrosine kinase inhibitor of VEGF receptor signaling. Our preliminary phase I trial data showed that adding cediranib to docetaxel plus prednisone (DP) was safe and feasible, with early evidence for efficacy in patients with metastatic castrate-resistant prostate cancer (mCRPC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicenter phase II trial assessed whether adding cediranib to DP improves efficacy of DP in patients with mCRPC. Chemotherapy-naive patients with mCRPC were randomly assigned to receive either docetaxel (75 mg\/m2 intravenously every 3 weeks) with prednisone (5 mg twice daily) plus cediranib (30 mg once daily; the DP+C arm) or DP only (the DP arm). The primary endpoint was to compare 6-month progression-free survival (PFS) rate between the two arms. Secondary endpoints included 6-month overall survival (OS), objective tumor and prostate-specific antigen (PSA) response rates, biomarkers, and adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The 6-month PFS rate in a total of 58 patients was only numerically higher in the DP+C arm (61%) compared with the DP arm (57%). Similarly, the 6-month OS rate, objective tumor and PSA response rates, and biomarkers were not significantly different between the two arms. Increased baseline levels of interleukin 6 (IL-6), however, were significantly associated with increased risk of progression. Neutropenia was the only grade 4 toxicity (38% in the DP+C arm vs. 18% in the DP arm).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Combining cediranib with docetaxel + prednisone failed to demonstrate superior efficacy, compared with docetaxel + prednisone, and added toxicity. Our data do not support pursuing the combination further in patients with mCRPC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1634\/theoncologist.2019-0331","type":"journal-article","created":{"date-parts":[[2019,5,31]],"date-time":"2019-05-31T15:15:50Z","timestamp":1559315750000},"page":"1149-e807","source":"Crossref","is-referenced-by-count":10,"title":["Phase II, Multicenter, Randomized Trial of Docetaxel plus Prednisone with or Without Cediranib in Men with Chemotherapy-Naive Metastatic Castrate-Resistant Prostate Cancer"],"prefix":"10.1093","volume":"24","author":[{"given":"Elisabeth","family":"Heath","sequence":"first","affiliation":[{"name":"Department of Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lance","family":"Heilbrun","sequence":"additional","affiliation":[{"name":"Department of Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Mannuel","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, University of Maryland School of Medicine and Greenebaum Cancer Center, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, University of Wisconsin School of Medicine and Public Health and Carbone Cancer Center, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Primo","family":"Lara","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, University of California Davis School of Medicine and Cancer Center, Sacramento, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Paul","family":"Monk","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Ohio State University School of Medicine and Cancer Center - James, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Flaig","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amado","family":"Zurita","sequence":"additional","affiliation":[{"name":"Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Mack","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, University of California Davis School of Medicine and Cancer Center, Sacramento, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulka","family":"Vaishampayan","sequence":"additional","affiliation":[{"name":"Department of Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Stella","sequence":"additional","affiliation":[{"name":"IHA Hematology\/Oncology, Ypsilanti, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daryn","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Bolton","sequence":"additional","affiliation":[{"name":"Department of Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arif","family":"Hussain","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, University of Maryland School of Medicine and Greenebaum Cancer Center, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anas","family":"Al-Janadi","sequence":"additional","affiliation":[{"name":"Michigan State University Breslin Cancer Center, Lansing, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Silbiger","sequence":"additional","affiliation":[{"name":"Case Western Reserve University School of Medicine University Hospitals, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Usman","sequence":"additional","affiliation":[{"name":"Department of Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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