Sustained complete remission of metastatic dermatofibrosarcoma protuberans with imatinib mesylate

Brigham and Women's Hospital, Boston, Massachusetts, United States
Anti-Cancer Drugs (Impact Factor: 1.78). 05/2005; 16(4):461-6. DOI: 10.1097/00001813-200504000-00014
Source: PubMed

ABSTRACT Dermatofibrosarcoma protuberans (DFSP) is a soft tissue tumor which may recur locally and rarely causes metastases to vital organs. DFSPs have specific chromosomal abnormalities involving the platelet-derived growth factor beta-chain locus (PDGFB) which may render these tumors responsive to targeted therapy with the tyrosine kinase inhibitor imatinib mesylate. A patient with locally recurrent and metastatic DFSP resistant to first-line chemotherapy was treated with imatinib mesylate 400 mg/day. The tumor was examined by a novel fluorescence in situ hybridization (FISH) method for specific rearrangements of the PDGFB locus. The patient was followed for response and toxicity by physical examination and imaging studies. FISH revealed PDGFB rearrangement indicative of multiplication of the PDGFB fusion locus within a ring chromosome. Physical examination showed response within the first month of treatment, and subsequent computed tomography and fluorodeoxyglycose positron emission tomography documented complete response to imatinib therapy. Our patient is now in sustained complete remission for 20 months with minimal toxicity. We conclude that sustained complete remission of metastatic DFSP with specific FISH abnormalities involving the PDGFB locus can be obtained with imatinib mesylate with minimal toxicity for the patient.

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    • "We identified 23 case reports [19,20,23-25,27,29-32,35,38,39,41,42,50-52], [55-59], 15 case series [16,26,33,34,36,37,45,47,53,60-65], 6 phase II studies [18,40,46,48,49] and 4 pediatric studies [28,43,44,54] where Imatinib was used for the treatment of patients with DFSP. These studies include a total of 199 patients. "
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    ABSTRACT: Dermatofibrosarcoma Protuberans (DFSP) is a rare skin tumor, characterized by frequent local recurrence but is seldom metastatic. It is histologically characterized by storiform arrangement of spindle cells. Cytogenetically, most tumors are characterized by translocation 17:22 leading to overexpression of tyrosine kinase PDGFB which can be targeted with tyrosine kinase inhibitor, Imatinib. We describe the first case of unresectable pancreatic metastases from DFSP treated with neoadjuvant Imatinib and subsequently R0 metastectomy. Additionally, a comprehensive systematic review of DFSP pancreatic metastases and the current published data on the use of Imatinib in DFSP is summarized.
    08/2014; 4(1):8. DOI:10.1186/2045-3329-4-8
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    • "The formation of COL1A1-PDGFB fusion gene results in the constitutional upregulation of PDGFB expression, leading to continuous autocrine activation of PDGF receptor B (PDGFRB) which is a key pathogenetic factor [46]. Based on the inhibitory effects of Imatinib on DFSP cell growth in various in vitro and in vivo studies [47], initial case reports showed the benefit of Imatinib in metastatic and locally advanced DFSP [48, 49]. In the largest retrospective series, 10 patients with locally advanced or metastatic DFSP received Imatinib 800 mg daily. "
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    ABSTRACT: Deregulated protein tyrosine kinase activity is central to the pathogenesis of human cancers. Targeted therapy in the form of selective tyrosine kinase inhibitors (TKIs) has transformed the approach to management of various cancers and represents a therapeutic breakthrough. Imatinib was one of the first cancer therapies to show the potential for such targeted action. Imatinib, an oral targeted therapy, inhibits tyrosine kinases specifically BCR-ABL, c-KIT, and PDGFRA. Apart from its remarkable success in CML and GIST, Imatinib benefits various other tumors caused by Imatinib-specific abnormalities of PDGFR and c-KIT. Imatinib has also been proven to be effective in steroid-refractory chronic graft-versus-host disease because of its anti-PDGFR action. This paper is a comprehensive review of the role of Imatinib in oncology.
    05/2014; 2014(2):357027. DOI:10.1155/2014/357027
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    • "In our case report (Labropoulos 2005), a patient with locally recurrent and metastatic to the lungs fibrosarcomatous DFSP was treated with imatinib at 400 mg/d. This patient was resistant to previous anthracycline chemotherapy and had both soft tissue and lung metastases. "
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    ABSTRACT: Dermatofibrosarcoma protuberans (DFSP) is a soft tissue tumor with tendency to recur locally and only rarely metastasizes to vital organs. Surgery with wide margins remains the standard treatment. DFSP is characterized by specific chromosomal abnormalities involving the platelet derived growth factor B locus (PDGFB). In the majority of cases a supernumerary ring chromosome containing amplified t(17; 22) translocation or a linear unbalanced t(17; 22) containing the COL1A1 -PDGFB fusion gene is present. This molecular event causes aberrant expression of a functional PDGFB leading to activation of PDGFR. Imatinib mesylate is a tyrosine kinase inhibitor with activity against activated PDGFR, and has significant activity against DFSP. Clinical evidence suggests that it has a role in locally advanced and metastatic disease and clinical trials are ongoing examining its role in this rare but potentially fatal sarcoma.
    Targets & therapy 01/2008; 1(4):347-53.
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