{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:29:46Z","timestamp":1787030986371,"version":"build-2736575974"},"reference-count":27,"publisher":"Innovative Healthcare Institute","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Metastatic urothelial carcinoma (mUC) has a poor prognosis with a 5-year survival probability of 4.8%. The mainstay of first-line treatment is platinum-based chemotherapy. Second-line therapy involves immune checkpoint inhibitors or a fibroblast growth factor receptor (FGFR) inhibitor, erdafitinib, for patients harboring selected FGFR alterations. Several additional agents are under development for the treatment of mUC. Recent studies demonstrate that ramucirumab and docetaxel have clinical activity in mUC. We report two patients with metastatic upper tract urothelial cancer (mUTUC) with FGFR alterations who were heavily pretreated with FGFR inhibitors that later showed response to ramucirumab and docetaxel. Preclinical studies indicate that FGF and VEGF pathways work synergistically, which could explain the observations in our patients. Our findings may represent another treatment option for patients with mUC and FGFR alterations who have progressed on multiple lines of therapy.<\/jats:p>","DOI":"10.4103\/jipo.jipo_22_19","type":"journal-article","created":{"date-parts":[[2020,1,7]],"date-time":"2020-01-07T02:56:20Z","timestamp":1578365780000},"page":"23-26","source":"Crossref","is-referenced-by-count":2,"title":["Ramucirumab and Docetaxel in Patients with Metastatic Urothelial Carcinoma Harboring Fibroblast Growth Factor Receptor Alterations: A Case Series and Literature Review"],"prefix":"10.36401","volume":"3","author":[{"given":"Katherine Emilie Rhoades","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie Elise","family":"Hitron","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greta A","family":"Russler","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A","family":"Baumgarten","sequence":"additional","affiliation":[{"name":"Department of Radiology, Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet Asim","family":"Bilen","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"22027","published-online":{"date-parts":[[2020,1,7]]},"reference":[{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b1","doi-asserted-by":"crossref","first-page":"E359","DOI":"10.1002\/ijc.29210","article-title":"Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012","volume":"136","author":"Ferlay","year":"2015","journal-title":"Int J Cancer"},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b2","article-title":"Key Statistics for Bladder Cancer","year":"2018"},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b3","article-title":"SEER Cancer Statistics Factsheets: Bladder Cancer"},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b4","unstructured":"National Comprehensive Cancer Network.\n          \n          The NCCN Clinical Practical Guidelines in Oncology Bladder Cancer (Version 5.2017).\n\t\t\t\t\tAvailable from: http:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/bladder.pdf; 2017. [Accessed Oct 27, 2018]."},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b5","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/tre.603","article-title":"Current management of advanced bladder cancer","volume":"8","author":"Waldron","year":"2017","journal-title":"Trends Urol Mens Health"},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b6","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1002\/phar.2033","article-title":"A review of immune checkpoint inhibitors for the management of locally advanced or metastatic urothelial carcinoma","volume":"37","author":"Hanna","year":"2017","journal-title":"Pharmacotherapy"},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b7","first-page":"4503","article-title":"First results from the primary analysis population of the phase 2 study of erdafitinib (ERDA; JNJ-42756493) in patients (pts) with metastatic or unresectable urothelial carcinoma (mUC) and FGFR alterations (FGFRalt)","volume":"36","author":"Siefker-Radtke","year":"2018","journal-title":"Clin Oncol"},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b8","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1056\/NEJMoa1817323","article-title":"Erdafitinib in locally advanced or metastatic urothelial carcinoma","volume":"381","author":"Loriot","year":"2019","journal-title":"N Engl J Med"},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b9","unstructured":"FDA Grants Accelerated Approval to Erdafitinib for Metastatic Urothelial Carcinoma.\n\t\t\t\t\tThe ASCO Post. Available from: https:\/\/www.ascopost.com\/News\/59934. [Accessed Jul 13, 2019]."},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b10","first-page":"4540","article-title":"Safety and efficacy of docetaxel+b-701, a selective inhibitor of FGFR3, in subjects with advanced or metastatic urothelial carcinoma","volume":"35","author":"Bellmunt","year":"2017","journal-title":"Clin Oncol"},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b11","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1111\/cas.13124","article-title":"ASP5878, a selective FGFR inhibitor, to treat FGFR3-dependent urothelial cancer with or without chemoresistance","volume":"108","author":"Kikuchi","year":"2017","journal-title":"Cancer Sci"},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b12","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1200\/JCO.2016.67.2048","article-title":"Evaluation of BGJ398, a fibroblast growth factor receptor 1\u20133 kinase inhibitor, in patients with advanced solid tumors harboring genetic alterations in fibroblast growth factor receptors: Results of a global phase I, dose-escalation and dose-expansion study","volume":"35","author":"Nogova","year":"2017","journal-title":"J Clin Oncol"},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b13","first-page":"4517","article-title":"Efficacy of BGJ398, a fibroblast growth factor receptor (FGFR) 1\u20133 inhibitor, in patients (pts) with previously treated advanced\/metastatic urothelial carcinoma (mUC) with FGFR3 alterations","volume":"34","author":"Pal","year":"2016","journal-title":"Clin Oncol"},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b14","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1158\/2159-8290.CD-18-0229","article-title":"Efficacy of BGJ398, a fibroblast growth factor receptor 1\u20133 inhibitor, in patients with previously treated advanced urothelial carcinoma with FGFR3 alterations","volume":"8","author":"Pal","year":"2018","journal-title":"Cancer Discov"},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b15","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1158\/2159-8290.CD-12-0362","article-title":"Fibroblast growth factor receptor inhibitors as a cancer treatment: From a biologic rationale to medical perspectives","volume":"3","author":"Dieci","year":"2013","journal-title":"Cancer Discov"},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b16","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1200\/JCO.2015.65.0218","article-title":"Docetaxel as monotherapy or combined with ramucirumab or icrucumab in second-line treatment for locally advanced or metastatic urothelial carcinoma: An open-label, three-arm, randomized controlled phase II trial","volume":"34","author":"Petrylak","year":"2016","journal-title":"J Clin Oncol"},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b17","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1016\/S0140-6736(17)32365-6","article-title":"Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): A randomised, double-blind, phase 3 trial","volume":"390","author":"Petrylak","year":"2017","journal-title":"Lancet"},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b18","unstructured":"Results from Phase III RANGE Study of Ramucirumab in Advanced or Metastatic Urothelial Cancer.\n\t\t\t\t\tThe ASCO Post. Available from: http:\/\/www.ascopost.com\/News\/58788; 2018. [Accessed Oct, 2018]."},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b19","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/wdev.176","article-title":"The fibroblast growth factor signaling pathway","volume":"4","author":"Ornitz","year":"2015","journal-title":"Wiley Interdiscip Rev Dev Biol"},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b20","doi-asserted-by":"crossref","first-page":"2684","DOI":"10.1158\/1078-0432.CCR-14-2329","article-title":"Targeting FGFR signaling in cancer","volume":"21","author":"Touat","year":"2015","journal-title":"Clin Cancer Res"},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b21","doi-asserted-by":"crossref","first-page":"16052","DOI":"10.18632\/oncotarget.14109","article-title":"Inhibition of the fibroblast growth factor receptor (FGFR) pathway: The current landscape and barriers to clinical application","volume":"8","author":"Chae","year":"2017","journal-title":"Oncotarget"},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b22","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1083\/jcb.141.7.1659","article-title":"Fibroblast growth factor-2 (FGF-2) induces vascular endothelial growth factor (VEGF) expression in the endothelial cells of forming capillaries: An autocrine mechanism contributing to angiogenesis","volume":"141","author":"Seghezzi","year":"1998","journal-title":"J Cell Biol"},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b23","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1016\/j.eururo.2017.01.021","article-title":"A functional genetic screen identifies the phosphoinositide 3-kinase pathway as a determinant of resistance to fibroblast growth factor receptor inhibitors in FGFR mutant urothelial cell carcinoma","volume":"71","author":"Wang","year":"2017","journal-title":"Eur Urol"},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b24","doi-asserted-by":"crossref","first-page":"15894","DOI":"10.1073\/pnas.1208324109","article-title":"Collaborative interplay between FGF-2 and VEGF-C promotes lymphangiogenesis and metastasis","volume":"109","author":"Cao","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b25","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1016\/S0002-9440(10)64325-8","article-title":"Distinct role of fibroblast growth factor-2 and vascular endothelial growth factor on tumor growth and angiogenesis","volume":"162","author":"Giavazzi","year":"2003","journal-title":"Am J Pathol"},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b26","doi-asserted-by":"crossref","first-page":"4007","DOI":"10.1074\/jbc.M307569200","article-title":"Fibroblast growth factor-2-mediated capillary morphogenesis of endothelial cells requires signals via Flt-1\/vascular endothelial growth factor receptor-1: Possible involvement of c-Akt","volume":"279","author":"Kanda","year":"2004","journal-title":"J Biol Chem"},{"key":"2021072618014647500_i2590-017X-3-1-case_report1-b27","doi-asserted-by":"crossref","first-page":"2668","DOI":"10.1172\/JCI44762","article-title":"FGF-dependent regulation of VEGF receptor 2 expression in mice","volume":"121","author":"Murakami","year":"2011","journal-title":"J Clin Invest"}],"container-title":["Journal of Immunotherapy and Precision Oncology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/meridian.allenpress.com\/innovationsjournals-JIPO\/article-pdf\/3\/1\/23\/2873290\/i2590-017x-3-1-case_report1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/meridian.allenpress.com\/innovationsjournals-JIPO\/article-pdf\/3\/1\/23\/2873290\/i2590-017x-3-1-case_report1.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T14:02:25Z","timestamp":1627308145000},"score":1,"resource":{"primary":{"URL":"https:\/\/meridian.allenpress.com\/innovationsjournals-JIPO\/article\/3\/1\/23\/434952\/Ramucirumab-and-Docetaxel-in-Patients-with"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,7]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1,7]]},"published-print":{"date-parts":[[2020,2,1]]}},"URL":"https:\/\/doi.org\/10.4103\/jipo.jipo_22_19","relation":{},"ISSN":["2666-2345","2590-017X"],"issn-type":[{"value":"2666-2345","type":"print"},{"value":"2590-017X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,7]]}}}