J Thorac Oncol. 2012 Apr;7(4):755-9.
Phase II Study of Dasatinib in Patients with Previously Treated MalignantMesothelioma (Cancer and Leukemia Group B 30601): A Brief Report.
Dudek AZ, Pang H, Kratzke RA, Otterson GA, Hodgson L, Vokes EE, Kindler HL; Cancer and Leukemia Group B.
Source
*Department of Medicine, University of Minnesota Masonic Cancer Center, Minneapolis, Minnesota †Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina ‡College of Medicine, Ohio State University, Columbus, Ohio §Department of Medicine, The University of Chicago, Chicago, Illinois.
Abstract
INTRODUCTION:
: We conducted a phase II trial of dasatinib in malignant mesothelioma (MM) patients to evaluate its toxicity and efficacy as a second-line treatment.
METHODS:
: Patients with unresectable MM and no symptomatic effusions were given dasatinib 70 mg twice daily as part of a 28-day cycle. We also measured plasma vascular endothelial growth factor and platelet-derived growth factor b and colony stimulating factor 1 (CSF-1) and mesothelin-related protein at baseline and during therapy.
RESULTS:
: Forty-six patients were enrolled in this study. Fifty percent of the first 12 patients enrolled experienced ≥grade 3 treatment-related adverse events, and therefore, the starting dose was reduced to 50 mg twice daily. Grade 3 and 4 toxicities included fatigue (11%) and pleural effusion (9%). The overall disease control rate was 32.6%, and progression-free survival at 24 weeks was 23% (95% confidence interval: 13.5-40.0%). Survival was markedly longer in patients with lower pretreatment CSF-1 levels and in patients whose CSF-1 levels decreased from baseline during therapy.
DISCUSSION:
: Single-agent dasatinib has no activity in MM and is associated with pulmonary toxicities that prohibit its use in an unselected MM population.
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