Rapamune™ May Improve Responses to Gleevec® in Patients with Chordoma

Researchers from Italy have reported that the addition of Rapamune® (sirolimus, rapamycin) to Gleevec® (imatinib) may improve disease control in patients with chordoma resistant to Gleevec. The details of this study appeared in the November 2009 issue of the Annals of Oncology.[1] 

Chordomas are rare slow-growing malignant tumors derived from the primitive notochord. These tumors are located along the neuroaxis.  Treatment usually involves surgical resection followed by radiotherapy; 10-year disease-free survival is 46%. Gleevec appears to have a modest effect for the treatment of patients with chordomas who fail surgery and radiotherapy. Researchers from Italy treated six patients with advanced chordoma with Gleevec.[2] These patients were treated for a year or more with evidence of activity with tumor liquifaction but no complete responses.

Rapamune is an immunosuppressive agent used in kidney transplants. Rapamune is an mTOR inhibitor; mTOR signaling is hyperactive in some chordomas. This has led to the current study of combining Gleevec with Rapamune in patients with chordoma who have failed treatment with Gleevec. The current study included 10 patients with progressive advanced chordoma who had failed treatment with Gleevec. All had laboratory evidence of upstream and/or downstream mTOR effector activation. Patients were treated for an average of nine months. One of nine evaluable patients had a clinical partial response, seven had stable disease, and one had progressive disease. By MRI there were seven partial responses, one stable disease, and one progressive disease. The overall clinical benefit was 89%. These authors concluded: “In addition to PDGFRB, mTOR pathway can be activated in chordomas and the combination of IM plus rapalogs may be effective in IM-resistant chordomas.”

Comments: These are important observations for the few patients who have chordomas that are not cured with surgery and radiotherapy.

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