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Article: A phase II study of sorafenib in malignant mesothelioma: Results of Cancer and Leukemia Group B 30307

TitleA phase II study of sorafenib in malignant mesothelioma: Results of Cancer and Leukemia Group B 30307
Authors
KeywordsClinical trial
Mesothelioma
Sorafenib
Tyrosine kinase inhibitor
Vascular endothelial growth factor
Issue Date2010
Citation
Journal of Thoracic Oncology, 2010, v. 5 n. 10, p. 1655-1661 How to Cite?
AbstractHypothesis: Malignant mesotheliomas (MMs) express vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and cKIT. Sorafenib is a potent inhibitor of the ras/raf/MEK pathway and also targets VEGFR and cKIT. We evaluated the activity of sorafenib in patients with unresectable mesothelioma. Methods: MM patients who had received 0 to 1 prior chemotherapy regimens were treated with sorafenib 400 mg orally twice daily continuously. The primary end point was objective response. ERK1/2 phosphorylation in archival tissues was correlated with response and survival. Results: A total of 51 patients were enrolled, 50 were evaluable and included in the analysis. Three patients had a partial response (6% [95% confidence interval = 1.3-16.6%]), and 27 (54% [95% confidence interval = 39.3-68.2%]) had stable disease. Median progression-free survival and median overall survival (OS) were 3.6 and 9.7 months, respectively. Median survival was superior in epithelioid histology versus other types (10.7 versus 3.7 months, p = 0.0179). The difference in median OS between pretreated and chemonaive patients was not statistically significant (13.2 versus 5 months, p = 0.3117). Low/negative baseline tumor phospho-ERK1/2 levels were associated with improved OS (13.9 versus 5.2 months, p = 0.0066). Conclusion: Sorafenib has limited activity in advanced MM patients, similar to that seen with other VEGFR tyrosine kinase inhibitors. Additional studies of sorafenib in MM are not warranted. Copyright © 2010 by the International Association for the Study of Lung Cancer.
Persistent Identifierhttp://hdl.handle.net/10722/194290
ISSN
2023 Impact Factor: 21.0
2023 SCImago Journal Rankings: 7.879
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorDubey, S-
dc.contributor.authorJänne, PA-
dc.contributor.authorKrug, L-
dc.contributor.authorPang, H-
dc.contributor.authorWang, X-
dc.contributor.authorHeinze, R-
dc.contributor.authorWatt, C-
dc.contributor.authorCrawford, J-
dc.contributor.authorKratzke, R-
dc.contributor.authorVokes, E-
dc.contributor.authorKindler, HL-
dc.date.accessioned2014-01-30T03:32:24Z-
dc.date.available2014-01-30T03:32:24Z-
dc.date.issued2010-
dc.identifier.citationJournal of Thoracic Oncology, 2010, v. 5 n. 10, p. 1655-1661-
dc.identifier.issn1556-0864-
dc.identifier.urihttp://hdl.handle.net/10722/194290-
dc.description.abstractHypothesis: Malignant mesotheliomas (MMs) express vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and cKIT. Sorafenib is a potent inhibitor of the ras/raf/MEK pathway and also targets VEGFR and cKIT. We evaluated the activity of sorafenib in patients with unresectable mesothelioma. Methods: MM patients who had received 0 to 1 prior chemotherapy regimens were treated with sorafenib 400 mg orally twice daily continuously. The primary end point was objective response. ERK1/2 phosphorylation in archival tissues was correlated with response and survival. Results: A total of 51 patients were enrolled, 50 were evaluable and included in the analysis. Three patients had a partial response (6% [95% confidence interval = 1.3-16.6%]), and 27 (54% [95% confidence interval = 39.3-68.2%]) had stable disease. Median progression-free survival and median overall survival (OS) were 3.6 and 9.7 months, respectively. Median survival was superior in epithelioid histology versus other types (10.7 versus 3.7 months, p = 0.0179). The difference in median OS between pretreated and chemonaive patients was not statistically significant (13.2 versus 5 months, p = 0.3117). Low/negative baseline tumor phospho-ERK1/2 levels were associated with improved OS (13.9 versus 5.2 months, p = 0.0066). Conclusion: Sorafenib has limited activity in advanced MM patients, similar to that seen with other VEGFR tyrosine kinase inhibitors. Additional studies of sorafenib in MM are not warranted. Copyright © 2010 by the International Association for the Study of Lung Cancer.-
dc.languageeng-
dc.relation.ispartofJournal of Thoracic Oncology-
dc.subjectClinical trial-
dc.subjectMesothelioma-
dc.subjectSorafenib-
dc.subjectTyrosine kinase inhibitor-
dc.subjectVascular endothelial growth factor-
dc.titleA phase II study of sorafenib in malignant mesothelioma: Results of Cancer and Leukemia Group B 30307-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1097/JTO.0b013e3181ec18db-
dc.identifier.pmid20736856-
dc.identifier.scopuseid_2-s2.0-77958167230-
dc.identifier.volume5-
dc.identifier.issue10-
dc.identifier.spage1655-
dc.identifier.epage1661-
dc.identifier.isiWOS:000282122000025-
dc.identifier.issnl1556-0864-

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