A phase II study of sorafenib in malignant mesothelioma: Results of Cancer and Leukemia Group B 30307 Journal Article
| Authors: | Dubey, S.; Jänne, P. A.; Krug, L.; Pang, H.; Wang, X.; Heinze, R.; Watt, C.; Crawford, J.; Kratzke, R.; Vokes, E.; Kindler, H. L. |
| Article Title: | A phase II study of sorafenib in malignant mesothelioma: Results of Cancer and Leukemia Group B 30307 |
| Abstract: | Hypothesis: 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. |
| Keywords: | immunohistochemistry; adult; cancer chemotherapy; cancer survival; human tissue; treatment outcome; treatment response; aged; middle aged; survival rate; major clinical study; overall survival; clinical trial; drug activity; fatigue; histopathology; sorafenib; cancer growth; hypertension; antineoplastic agents; benzenesulfonates; pyridines; cancer patient; neoplasm staging; anorexia; drug inhibition; progression free survival; multiple cycle treatment; pain; phase 2 clinical trial; sensory neuropathy; peritoneal neoplasms; hemolysis; continuous infusion; phosphorylation; histology; dyspnea; lymphocytopenia; rash; hypotension; enzyme phosphorylation; vascular endothelial growth factor; pleura mesothelioma; mesothelioma; mitogen activated protein kinase 1; mitogen activated protein kinase 3; extracellular signal-regulated map kinases; tyrosine kinase inhibitor; pleural neoplasms; hemoglobinopathy |
| Journal Title: | Journal of Thoracic Oncology |
| Volume: | 5 |
| Issue: | 10 |
| ISSN: | 1556-0864 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2010-10-01 |
| Start Page: | 1655 |
| End Page: | 1661 |
| Language: | English |
| DOI: | 10.1097/JTO.0b013e3181ec18db |
| PUBMED: | 20736856 |
| PROVIDER: | scopus |
| PMCID: | PMC3823555 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 20 April 2011" - "Source: Scopus" |
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