Differential sensitivity to imatinib of 2 patients with metastatic sarcoma arising from dermatofibrosarcoma protuberans

• Published in: International journal of cancer Vol. 100; no. 6; pp. 623 - 626
• Main Authors: Maki, Robert G., Awan, Rashid A., Dixon, Richard H., Jhanwar, Suresh, Antonescu, Cristina R.
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 20.08.2002; Wiley-Liss
• Subjects: Adult; Antineoplastic agents; Antineoplastic Agents - pharmacology; Benzamides; Biological and medical sciences; Chemotherapy; Dermatofibrosarcoma - drug therapy; Dermatofibrosarcoma - pathology; dermatofibrosarcoma protuberans; Humans; imatinib; Imatinib Mesylate; Immunohistochemistry; Male; Medical sciences; PDGF receptor; Pharmacology. Drug treatments; Piperazines - pharmacology; Platelet-Derived Growth Factor - metabolism; Pyrimidines - pharmacology; Recurrence; Sarcoma - drug therapy; Sarcoma - secondary; Skin Neoplasms - drug therapy; soft tissue sarcoma; STI‐571; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; tyrosine kinase; Antineoplastic agent; Human; Skin disease; Sarcoma; Enzyme; Transferases; Cytokine; Imatinib mesylate; Enzyme inhibitor; Malignant tumor; Chemotherapy; Growth factor receptor; Treatment; Advanced stage; Soft tissue; Dermatofibrosarcoma protuberans; Protein-tyrosine kinase; Platelet derived growth factor; Growth factor; Biological receptor
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.10535

Dermatofibrosarcoma protuberans (DFSP) is a rare superficial sarcoma usually affecting the trunk, with significant risk of local recurrence. It is characterized by the presence of ring chromosomes or chromosomal translocations fusing the promoter of the collagen gene COL1A1 to the platelet‐derived growth factor β‐chain gene PDGFB, increasing the production of PDGF locally and promoting autocrine or paracrine tumor growth. Fewer than 5% of patients with DFSP develop metastatic sarcoma, with a poor subsequent prognosis. Imatinib (STI‐571) was developed as an inhibitor of the PDGF receptor tyrosine kinase and has proven clinical activity against chronic myelogenous leukemia (expressing bcr‐abl) and gastrointestinal stromal tumors (expressing c‐kit). We describe 2 patients with metastatic and unresectable metastases from DFSP treated with imatinib. After confirmation of negative CD117 status of 2 sarcomas arising from DFSP, patients were given imatinib 400 mg po qd and assessed at regular intervals for their tolerance and response to therapy. One patient had a transient response, then progressed rapidly and died of disease. Another patient showed a partial response to therapy after 2 months, with resolution of superior vena cava syndrome and shrinking of metastatic lung lesions. His response is ongoing after 6 months of therapy. These clinical data confirm findings from models of DFSP and support the use of imatinib in the rare setting of metastatic DFSP. Imatinib may be useful for patients with locally advanced DFSP, when other options for local therapy are limited. © 2002 Wiley‐Liss, Inc.