2002 CTOS Annual Meeting Oral Presentations — Medical Oncology

Molecular Targeting Of Pdgfb By Imatinib Mesylate In Dermatofibrosarcoma Protuberans
[Abstract ID: 25]

Category: Medical Oncology

Presentation: Young Investigator

Authors: Scott M Schuetze¹, Brian P Rubin¹, Janet F Eary¹, Thomas H Norwood¹, Sohail Mirza¹, Ernest U Conrad III¹, James D Bruckner¹

Author Institutions: ¹University of Washington, Seattle, Washington, United States

Presenter: Scott M Schuetze
sschuetz@fhcrc.org

Correspondent: Scott M Schuetze
sschuetz@fhcrc.org
Seattle Washington United States 98109
Ph: 206 288-2052
Fax: 206 288-2042

Objectives: Dermatofibrosarcoma protuberans (DFSP) are highly invasive dermal mesenchymal neoplasms that occasionally metastasize. Standard chemotherapy has not been effective. Activation of the platelet derived growth factor B (PDGFB) receptor, a transmembrane kinase, by aberrant expression of platelet derived growth factor B is central to the pathogenesis of DFSP. We treated a patient with unresectable, metastatic DFSP with imatinib mesylate to investigate the response of this malignancy to inhibition of the PDGFB pathway.

Methods: A patient with metastatic DFSP received imatinib mesylate twice daily. Tumor response to therapy was assessed using fluorodeoxyglucose-positron emission tomography, magnetic resonance imaging, immunohistochemistry and standard pathology.

Results: The patient tolerated twice daily ingestion of imatinib mesylate. After two weeks of treatment, fluorodeoxyglucose uptake in the DFSP fell to background levels. Tumor volume progressively shrank over four months by more than 75% allowing for complete resection of the residual mass. Histologic evaluation revealed a complete pathologic response to treatment. Adjuvant therapy with imatinib mesylate was not used. The patient remains free of tumor more than nine months after surgery.

Conclusions: Imatinib mesylate appears to be highly active in DFSP when administered twice daily. The optimal duration of therapy to obtain a complete response is not known, but in this patient, four months of treatment resulted in a complete histologic response and allowed for complete resection of the residual mass. This result demonstrates that therapies targeting specific oncogene pathways central to the pathogenesis of a neoplasm can result in dramatic therapeutic effects.