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A phase 2 trial of imatinib mesylate in patients with recurrent nonresectable chondrosarcomas expressing platelet-derived growth factor receptor-α or -β
An Italian Sarcoma Group study
Article first published online: 5 OCT 2010
Copyright © 2010 American Cancer Society
Volume 117, Issue 4, pages 826–831, 15 February 2011
How to Cite
Grignani, G., Palmerini, E., Stacchiotti, S., Boglione, A., Ferraresi, V., Frustaci, S., Comandone, A., Casali, P. G., Ferrari, S. and Aglietta, M. (2011), A phase 2 trial of imatinib mesylate in patients with recurrent nonresectable chondrosarcomas expressing platelet-derived growth factor receptor-α or -β. Cancer, 117: 826–831. doi: 10.1002/cncr.25632
- Issue published online: 3 FEB 2011
- Article first published online: 5 OCT 2010
- Manuscript Accepted: 3 AUG 2010
- Manuscript Revised: 19 JUL 2010
- Manuscript Received: 28 MAY 2010
- imatinib mesylate;
- targeted therapy;
- platelet-derived growth factor receptor (PDGFR)-α;
Chondrosarcoma (CS) is a rare and heterogeneous sarcoma in which, after failure of surgery and radiotherapy, chemotherapy plays only a marginal role. Different molecular pathways have been shown to be activated in CS; in particular, both isoforms of platelet-derived growth factor receptor (PDGFR) are expressed and phosphorylated. These observations prompted investigation of the activity of imatinib mesylate (IM) in patients with advanced CS in a phase 2 trial.
Between January 2007 and June 2009, patients with metastatic, nonresectable CS were treated with 400 mg of IM administered twice daily until disease progression or unacceptable toxicity. Two criteria determined patient trial eligibility: ≥1 prior line of chemotherapy and immunohistochemical expression of either PDGFR-α or PDGFR-β. The primary objective of the trial was objective response. As secondary objectives, the authors selected progression-free survival (PFS) at 4 months, overall survival, and clinical benefit (EUDRACT number 2006-006446-33).
Twenty-six patients were enrolled and all demonstrated PDGFR positivity and phosphorylation. No objective response was demonstrated. The 4-month PFS rate was 31% (95% confidence interval [95% CI], 16%-53%). The median overall survival was 11 months (95% CI, 6 months-15 months). Neither long-lasting freedom from disease progression nor clinical benefit was observed. The IM dose was temporarily reduced in 60%15 of the patients because of toxicity.
IM was found to be relatively well-tolerated, but failed to demonstrate meaningful clinical activity in terms of both objective response and freedom from disease progression. Advanced CS remains an incurable disease, and effective targeted therapies are still awaited. Cancer 2011. © 2010 American Cancer Society.