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03 - Systemic treatment approaches for unresectable...

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Official reprint from UpToDate ® www.uptodate.com ©2010 UpToDate ® Authors Nicholas Vogelzang, MD Lin-Chi Chen, MD, PhD Section Editor Arthur T Skarin, MD Deputy Editor Michael E Ross, MD Systemic treatment approaches for unresectable malignant mesothelioma Last literature review version 18.1: Ocak 2010 | This topic last updated: Ocak 4, 2010 INTRODUCTION — Malignant mesothelioma is a rare neoplasm that arises most commonly from the mesothelial surfaces of the pleural cavity, occasionally from the peritoneal surface, and rarely from the tunica vaginalis or pericardium. It has an extremely poor prognosis; the median survival is 4 to 13 months for untreated patients [ 1 ] and 6 to 18 months for treated patients, regardless of the therapeutic approach [ 2,3 ]. The systemic treatment approaches for advanced unresectable pleural and peritoneal malignant mesothelioma will be reviewed here. Approaches to localized disease, and the epidemiology, pathology, clinical presentation, and staging of this disorder are discussed separately. (See "Treatment approaches for localized malignant pleural mesothelioma and solitary fibrous tumor of the pleura" and "Clinical presentation, diagnosis, and staging of malignant pleural mesothelioma" and "Epidemiology of malignant mesothelioma" .) PLEURAL MESOTHELIOMA — The development of systemic treatment for pleural mesothelioma has been difficult because of the limited numbers of patients, difficulties in determining whether an individual patient is benefiting from treatment, and the poor prognosis associated with advanced disease [ 1,4,5 ]. Response assessment — The definitive approach to assess the value of a new agent or combination regimen in patients with mesothelioma is the demonstration of a survival benefit in a randomized trial [ 6 ]. Both the objective response rate (as measured on CT scan by a decrease of >30 percent in the thickness of the pleural rind perpendicular to the rib cage) and progression-free survival have been used as surrogates for efficacy in all the phase III studies to date [ 7 ]. The use of positron emission tomography combined with CT scanning (PET/CT) to detect a decrease in metabolic activity in the tumor may be a better predictor of time to progression rather than objective response as determined by computed tomography alone [ 8 ]. However the PET/CT endpoint has never been validated in phase III trials. The heterogeneity of study populations in different studies has limited the interpretation of results. Analyses from the Cancer and Leukemia Group B (CALGB) and the European Organization for Research and Treatment of Cancer (EORTC) have allowed identification of the key prognostic factors and improved the ability to compare and generalize results among clinical trials ( table 1 and table 2 ) [ 9-11 ].
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