SEARCH

SEARCH BY CITATION

Keywords:

  • imatinib mesylate;
  • chondrosarcoma;
  • targeted therapy;
  • platelet-derived growth factor receptor (PDGFR)-α;
  • PDGFR-β

Abstract

BACKGROUND.

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.

METHODS.

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).

RESULTS.

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.

CONCLUSIONS.

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.