{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T03:43:56Z","timestamp":1793072636273,"version":"4.5.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2021,12,25]],"date-time":"2021-12-25T00:00:00Z","timestamp":1640390400000},"content-version":"vor","delay-in-days":1104,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Antiangiogenesis tyrosine kinase inhibitors (TKIs) have been shown to prolong progression-free survival (PFS) in advanced osteosarcoma. Methylsulfonic apatinib is a TKI that specifically inhibits vascular endothelial growth factor receptor-2. We aim to assess apatinib in patients with advanced high-grade osteosarcoma progressing upon chemotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>This phase II trial was conducted at Peking University People's Hospital. We enrolled participants (\u226516 years of age) with progressive relapsed or unresectable osteosarcoma. Participants received 750 mg or 500 mg of apatinib according to body surface area once daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate and PFS at 4 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 37 participants were finally included into the analysis. Until final follow-up, the objective response rate (complete response + partial response) was 43.24% (16\/37). The 4-month PFS rate was 56.76% (95% confidence interval [CI], 39.43%\u201370.84%). Median PFS and overall survival were 4.50 (95% CI, 3.47\u20136.27) and 9.87 (95% CI 7.97\u201318.93) months, respectively. Toxic effects led to dose reductions or interruptions in a total of 25 of 37 (67.57%) patients. The most common grade 3\u20134 adverse events were pneumothorax in six (16.22%) patients, wound dehiscence in four (10.81%), proteinuria in three (8.11%), diarrhea in three (8.11%), and palmar-plantar erythrodysesthesia syndrome in three (8.11%). No other serious adverse events were reported during the trial. There were no treatment-related deaths.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Apatinib is a sensitive drug for advanced osteosarcoma with a high response rate after failure of chemotherapy, with similar duration of response compared to other TKIs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1634\/theoncologist.2018-0542","type":"journal-article","created":{"date-parts":[[2018,12,17]],"date-time":"2018-12-17T17:09:35Z","timestamp":1545066575000},"page":"e542-e550","source":"Crossref","is-referenced-by-count":111,"title":["Apatinib for Advanced Osteosarcoma after Failure of Standard Multimodal Therapy: An Open Label Phase II Clinical Trial"],"prefix":"10.1093","volume":"24","author":[{"given":"Lu","family":"Xie","sequence":"first","affiliation":[{"name":"Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xu","sequence":"additional","affiliation":[{"name":"Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Sun","sequence":"additional","affiliation":[{"name":"Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Tang","sequence":"additional","affiliation":[{"name":"Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiqiang","family":"Yan","sequence":"additional","affiliation":[{"name":"Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongli","family":"Yang","sequence":"additional","affiliation":[{"name":"Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Guo","sequence":"additional","affiliation":[{"name":"Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,12,17]]},"reference":[{"key":"2021122507240811800_R1","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.spinee.2016.11.002","article-title":"Prognostic determinants and treatment outcomes analysis of osteosarcoma and Ewing sarcoma of the spine","volume":"17","author":"Arshi","year":"2017","journal-title":"Spine J"},{"key":"2021122507240811800_R2","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.ctrv.2013.11.006","article-title":"Osteosarcoma treatment - Where do we stand? A state of the art review","volume":"40","author":"Luetke","year":"2014","journal-title":"Cancer Treat Rev"},{"key":"2021122507240811800_R3","article-title":"Results of randomized, placebo (PL)-controlled phase II study evaluating efficacy and safety of regorafenib (REG) in patients (pts) with metastatic osteosarcoma (metOS), on behalf of the French Sarcoma Group (FSG) and Unicancer","author":"Duffaud","year":"2018","journal-title":"Abstract presented at ASCO 2018 Annual Meeting"},{"key":"2021122507240811800_R4","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1200\/JCO.2007.11.9230","article-title":"Phase I trial and pharmacokinetic study of bevacizumab in pediatric patients with refractory solid tumors: A Children's Oncology Group Study","volume":"26","author":"Glade Bender","year":"2008","journal-title":"J Clin Oncol"},{"key":"2021122507240811800_R5","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1080\/07357900600632058","article-title":"Evaluation of gefitinib for treatment of refractory solid tumors and central nervous system malignancies in pediatric patients","volume":"24","author":"Freeman","year":"2006","journal-title":"Cancer Invest"},{"key":"2021122507240811800_R6","doi-asserted-by":"crossref","first-page":"5174","DOI":"10.1200\/JCO.2010.30.9674","article-title":"A phase 1 trial and pharmacokinetic study of cediranib, an orally bioavailable pan-vascular endothelial growth factor receptor inhibitor, in children and adolescents with refractory solid tumors","volume":"28","author":"Fox","year":"2010","journal-title":"J Clin Oncol"},{"key":"2021122507240811800_R7","doi-asserted-by":"crossref","first-page":"5113","DOI":"10.1158\/1078-0432.CCR-11-0237","article-title":"Phase I and pharmacokinetic study of sunitinib in pediatric patients with refractory solid tumors: A children's oncology group study","volume":"17","author":"Dubois","year":"2011","journal-title":"Clin Cancer Res"},{"key":"2021122507240811800_R8","doi-asserted-by":"crossref","first-page":"625","DOI":"10.3892\/or.2017.5735","article-title":"Anti-angiogenesis target therapy for advanced osteosarcoma (Review)","volume":"38","author":"Xie","year":"2017","journal-title":"Oncol Rep"},{"key":"2021122507240811800_R9","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1093\/annonc\/mdr151","article-title":"A phase II trial of sorafenib in relapsed and unresectable high-grade osteosarcoma after failure of standard multimodal therapy: An Italian Sarcoma Group study","volume":"23","author":"Grignani","year":"2012","journal-title":"Ann Oncol"},{"key":"2021122507240811800_R10","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/S1470-2045(14)71136-2","article-title":"Sorafenib and everolimus for patients with unresectable high-grade osteosarcoma progressing after standard treatment: A non-randomised phase 2 clinical trial","volume":"16","author":"Grignani","year":"2015","journal-title":"Lancet Oncol"},{"key":"2021122507240811800_R11","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s10456-017-9552-y","article-title":"Anti-angiogenesis for cancer revisited: Is there a role for combinations with immunotherapy?","volume":"20","author":"Ramjiawan","year":"2017","journal-title":"Angiogenesis"},{"key":"2021122507240811800_R12","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.ccell.2014.10.006","article-title":"Antiangiogenesis strategies revisited: From starving tumors to alleviating hypoxia","volume":"26","author":"Jain","year":"2014","journal-title":"Cancer Cell"},{"key":"2021122507240811800_R13","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13569-016-0064-0","article-title":"Response to anti-PD1 therapy with nivolumab in metastatic sarcomas","volume":"6","author":"Paoluzzi","year":"2016","journal-title":"Clin Sarcoma Res"},{"key":"2021122507240811800_R14","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1245\/s10434-006-9227-1","article-title":"Small molecule tyrosine kinase inhibitors in the treatment of solid tumors: An update of recent developments","volume":"14","author":"Steeghs","year":"2007","journal-title":"Ann Surg Oncol"},{"key":"2021122507240811800_R15","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s004320050036","article-title":"Patterns of expression and secretion of vascular endothelial growth factor in malignant soft-tissue tumours","volume":"126","author":"Kuhnen","year":"2000","journal-title":"J Cancer Res Clin Oncol"},{"key":"2021122507240811800_R16","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1007\/s00432-003-0504-0","article-title":"Determination of vascular endothelial growth factor (VEGF) overexpression in soft tissue sarcomas and the role of overexpression in leiomyosarcoma","volume":"130","author":"Potti","year":"2004","journal-title":"J Cancer Res Clin Oncol"},{"key":"2021122507240811800_R17","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1124\/dmd.112.050310","article-title":"Metabolism and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor apatinib in humans","volume":"41","author":"Ding","year":"2013","journal-title":"Drug Metab Dispos"},{"key":"2021122507240811800_R18","doi-asserted-by":"crossref","DOI":"10.1038\/cddis.2017.422","article-title":"Apatinib promotes autophagy and apoptosis through VEGFR2\/STAT3\/BCL-2 signaling in osteosarcoma","volume":"8","author":"Liu","year":"2017","journal-title":"Cell Death Dis"},{"key":"2021122507240811800_R19","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1200\/JCO.2013.48.8585","article-title":"Apatinib for chemotherapy-refractory advanced metastatic gastric cancer: Results from a randomized, placebo-controlled, parallel-arm, phase II trial","volume":"31","author":"Li","year":"2013","journal-title":"J Clin Oncol"},{"key":"2021122507240811800_R20","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1200\/JCO.2015.63.5995","article-title":"Randomized, double-blind, placebo-controlled phase III trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction","volume":"34","author":"Li","year":"2016","journal-title":"J Clin Oncol"},{"key":"2021122507240811800_R21","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1080\/15384047.2017.1416275","article-title":"Efficacy and safety of apatinib monotherapy in advanced bone and soft tissue sarcoma: An observational study","volume":"19","author":"Zhu","year":"2017","journal-title":"Cancer Biol Ther"},{"key":"2021122507240811800_R22","doi-asserted-by":"crossref","first-page":"64471","DOI":"10.18632\/oncotarget.16293","article-title":"Efficacy and safety of Apatinib in stage IV sarcomas: Experience of a major sarcoma center in China","volume":"8","author":"Li","year":"2017","journal-title":"Oncotarget"},{"key":"2021122507240811800_R23","doi-asserted-by":"crossref","first-page":"50314","DOI":"10.18632\/oncotarget.18599","article-title":"Advanced alveolar soft part sarcoma responds to apatinib","volume":"8","author":"Zhou","year":"2017","journal-title":"Oncotarget"},{"key":"2021122507240811800_R24","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur J Cancer"},{"key":"2021122507240811800_R25","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1016\/0959-8049(92)90510-9","article-title":"Can Karnofsky performance status be transformed to the Eastern Cooperative Oncology Group scoring scale and vice versa?","volume":"28A","author":"Verger","year":"1992","journal-title":"Eur J Cancer"},{"key":"2021122507240811800_R26","volume-title":"Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03","author":"U.S. Department of Health and Human Services","year":"2010"},{"key":"2021122507240811800_R27","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0157359","article-title":"Reliability and validity of amharic version of EORTC QLQ-C 30 questionnaire among gynecological cancer patients in Ethiopia","volume":"11","author":"Ayana","year":"2016","journal-title":"PLoS One"},{"key":"2021122507240811800_R28","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/1477-7525-8-68","article-title":"Reliability of 95% confidence interval revealed by expected quality-of-life scores: An example of nasopharyngeal carcinoma patients after radiotherapy using EORTC QLQ-C 30","volume":"8","author":"Chien","year":"2010","journal-title":"Health Qual Life Outcomes"},{"key":"2021122507240811800_R29","first-page":"287","article-title":"The quality of life in head and neck cancer patients: Description of randomized examination formula based on standardized questionnaires EORTC QLQ C-30, EORTC QTQ-H-N35 and Kiel Questionnaire [in Polish]","volume":"55","author":"Wierzbicka","year":"2001","journal-title":"Otolaryngol Pol"},{"key":"2021122507240811800_R30","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1016\/j.ejca.2012.03.022","article-title":"Results of a phase II study of sirolimus and cyclophosphamide in patients with advanced sarcoma","volume":"48","author":"Schuetze","year":"2012","journal-title":"Eur J Cancer"},{"key":"2021122507240811800_R31","doi-asserted-by":"crossref","DOI":"10.5812\/aapm.38886","article-title":"Validation of a new \u201cobjective pain score\u201d vs. \u201cnumeric rating scale\u201d for the evaluation of acute pain: A comparative study","volume":"6","author":"Ruan","year":"2016","journal-title":"Anesth Pain Med"},{"key":"2021122507240811800_R32","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1186\/s12885-018-4303-z","article-title":"Apatinib for advanced sarcoma: Results from multiple institutions\u2019 off-label use in China","volume":"18","author":"Xie","year":"2018","journal-title":"BMC Cancer"}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1634\/theoncologist.2018-0542","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1634\/theoncologist.2018-0542","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/24\/7\/e542\/41917125\/oncolo_24_7_e542.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/24\/7\/e542\/41917125\/oncolo_24_7_e542.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,25]],"date-time":"2021-12-25T02:25:31Z","timestamp":1640399131000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/24\/7\/e542\/6439372"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,17]]},"references-count":32,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2018,12,17]]},"published-print":{"date-parts":[[2019,7,1]]}},"URL":"https:\/\/doi.org\/10.1634\/theoncologist.2018-0542","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.734656615.793579338","asserted-by":"object"}]},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"value":"1083-7159","type":"print"},{"value":"1549-490X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,7,1]]},"published":{"date-parts":[[2018,12,17]]}}}