Efficacy of imatinib mesylate for the treatment of locally advanced and/or metastatic tenosynovial giant cell tumor/pigmented villonodular synovitis

• Published in: Cancer Vol. 118; no. 6; pp. 1649 - 1655
• Main Authors: Cassier, Philippe A., Gelderblom, Hans, Stacchiotti, Silvia, Thomas, David, Maki, Robert G., Kroep, Judith R., van der Graaf, Winette T., Italiano, Antoine, Seddon, Beatrice, Dômont, Julien, Bompas, Emanuelle, Wagner, Andrew J., Blay, Jean‐Yves
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.03.2012; Wiley-Blackwell; Wiley
• Subjects: Adult; Aged; Antineoplastic Agents; Antineoplastic Agents - therapeutic use; Benzamides; Biological and medical sciences; Cancer; colony‐stimulating factor 1; colony‐stimulating factor 1 receptor; Diseases of the osteoarticular system; drug therapy; Female; Fluorodeoxyglucose F18; Giant Cell Tumors; Giant Cell Tumors - drug therapy; Giant Cell Tumors - pathology; Humans; imatinib; Imatinib Mesylate; Inflammatory joint diseases; Life Sciences; Male; Medical sciences; Middle Aged; Neoplasm Metastasis; pigmented villonodular synovitis; Piperazines; Piperazines - adverse effects; Piperazines - pharmacology; Piperazines - therapeutic use; Pyrimidines; Pyrimidines - adverse effects; Pyrimidines - pharmacology; Pyrimidines - therapeutic use; Receptor, Macrophage Colony-Stimulating Factor; Receptor, Macrophage Colony-Stimulating Factor - antagonists & inhibitors; Retrospective Studies; Synovitis, Pigmented Villonodular; Synovitis, Pigmented Villonodular - drug therapy; tenosynovial giant cell tumor; Tumors; Antineoplastic agent; Diseases of the osteoarticular system; Pharmacotherapy; Inflammatory joint disease; Metastasis; Cancerology; Giant cell tumor; colony-stimulating factor 1; Advanced stage; Protein-tyrosine kinase; Biological receptor; Imatinib; drug therapy; Enzyme; Tyrosine kinase inhibitor; Transferases; Treatment efficiency; Enzyme inhibitor; Malignant tumor; Pigmented villonodular synovitis; tenosynovial giant cell tumor; Chronic; Treatment; colony-stimulating factor 1 receptor; Locally advanced stage; Macrophage colony stimulating factor; Cancer
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.26409

BACKGROUND: Pigmented villonodular synovitis (PVNS) (also known as diffuse‐type giant cell tumor) and tenosynovial giant cell tumors (TGCT) are rare, usually benign neoplasms that affect the synovium and tendon sheaths in young adults. These tumors are driven by the overexpression of colony stimulating factor‐1 (CSF1). CSF1 is expressed by a minority of tumor cells, which, in turn attract non‐neoplastic inflammatory cells that express CSF1 receptor (CSF1R) through a paracrine effect. METHODS: Imatinib mesylate (IM) blocks CSF1R, and previous case reports indicated that it also exerts antitumor activity in PVNS. The authors conducted a multi‐institutional retrospective study to assess the activity of IM in patients with locally advanced/metastatic PVNS/TGCT. RESULTS: Twenty‐nine patients from 12 institutions in Europe, Australia, and the United States were included. There were 13 men, the median age was 41 years, and the most common site of disease was the knee (n = 17; 59%). Two patients had metastatic disease to the lung and/or bone. Five of 27 evaluable patients had Response Evaluation in Solid Tumor (RECIST) responses (overall response rate, 19%; 1 complete response and 4 partial responses), and 20 of 27 patients (74%) had stable disease. Symptomatic improvement was noted in 16 of 22 patients (73%) who were assessable for symptoms. Despite a high rate of symptomatic improvement and a favorable safety profile, 6 patients discontinued because of toxicity, and 4 patients decided to discontinue IM for no clear medical reason. CONCLUSIONS: IM displayed interesting activity in patients with PVNS/TGCT, providing proof of concept for targeting CSF1R in this disease. The authors concluded that the benefits of alleviating morbidity in patients with localized PVNS/TGCT must be balanced against the potential toxicity of chronic drug therapy. Cancer 2011;. © 2011 American Cancer Society. Tenosynovial giant cell tumors are rare, usually benign neoplasms in which a few tumor cells that harbor a collagen type I α1‐colony stimulating factor‐1 translocation recruit inflammatory cells through a landscape effect. This study demonstrates that imatinib mesylate, an inhibitor of the colony stimulating factor‐1 receptor, has clinical activity in this disease.