Phase II Study of Dasatinib in Patients with Previously Treated Malignant Mesothelioma (Cancer and Leukemia Group B 30601) A Brief Report

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 beta 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.