Sustained complete remission of metastatic dermatofibrosarcoma protuberans with imatinib mesylate
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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ABSTRACT: Dermatofibrosarcoma is a rare low-grade sarcoma characterized in more than 90% of cases by (17q22; 22q13) translocation leading to a fusion transcript COL1A1-PDGFB. Surgical therapy is the standard of care; however, tyrosine-kinase inhibitors targeting PDGFR are of interest in unresectable or rare metastatic tumors. Imatinib mesylate has been approved in this indication and research is going on with other inhibitors.Oncologie 02/2013; 15(2). DOI:10.1007/s10269-013-2251-4
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ABSTRACT: Renal cell carcinoma (RCC) is characterized by increased expression of vascular endothelial growth factor and platelet-derived growth factor (PDGF)-beta, both of which contribute to its angiogenic phenotype. Interferon-alpha (IFN-alpha) improves survival in patients with metastatic RCC, perhaps partly because of its antiangiogenic properties. Imatinib mesylate inhibits PDGF-mediated signal transduction and might thus have antiangiogenic activity as well. Patients with metastatic RCC were treated with IFN-alpha (9 million IU subcutaneously 3 times weekly) and oral imatinib mesylate (600 mg daily starting on day 8). Therapy was continuous, and response was evaluated at 8-week intervals using the Response Evaluation Criteria in Solid Tumors. Baseline plasma PDGF-AA, PDGF-AB, and PDGF-BB levels were obtained. Between January 2003 and January 2005, 17 patients were treated. One patient (6%) had a partial response, 4 (24%) had stable disease, 7 (41%) had progressive disease, and 5 (29%) were unevaluable because of early withdrawal secondary to toxicity. Median time to progression (TTP) using the Kaplan-Meier method was 8 weeks, and median overall survival was 17.8 months. Six patients (35%) withdrew from therapy because of toxicity, and 9 patients (53%) experienced > or = 1 grade 3/4 toxicity. Platelet-derived growth factor AA, AB, and BB plasma levels did not correlate with TTP or overall survival. Based on a response rate of only 6%, a median TTP of 2 months, and significant toxicities, further study of IFN-alpha in combination with imatinib mesylate is not recommended in patients with metastatic RCC.Clinical Genitourinary Cancer 03/2006; 4(4):275-80. DOI:10.3816/CGC.2006.n.007
Article: Primary cutaneous sarcomas[Show abstract] [Hide abstract]
ABSTRACT: Os sarcomas com apresentação cutânea primária são tumores raros e de grande heterogeneidade histológica. Com a evolução da oncologia cutânea e da cirurgia dermatológica, os dermatologistas têm sido cada vez mais requisitados para o diagnóstico e orientação terapêutica de tumores menos freqüentes. Este artigo de revisão analisa os sarcomas cutâneos primários observando suas características clínicas, etiopatogênicas e histológicas, bem como aspectos do tratamento e evolução. Enfatiza os sarcomas de maior relevância para o dermatologista, como angiossarcoma, dermatofibrossarcoma protuberans, fibroxantoma atípico, leiomiossarcoma, lipossarcoma, tumor maligno de bainha de nervo periférico e sarcoma epitelióide. O sarcoma de Kaposi não é abordado devido a suas características individuais específicas.Anais Brasileiros de Dermatologia 06/2006; 81(3):207-221.