Department of Medicine, Léon Bérard Center, Lyon, France.
Cancer. 2012 Mar 15;118(6):1649-55. doi: 10.1002/cncr.26409. Epub 2011 Aug 5.
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.
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.
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.
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.
色素绒毛结节性滑膜炎（PVNS）（也称为弥漫型巨细胞瘤）和腱鞘巨细胞瘤（TGCT）是罕见的，通常良性的肿瘤，影响滑膜和肌腱鞘在年轻成年人。这些肿瘤是由集落刺激因子-1（CSF1）的过度表达驱动的。CSF1 由少数肿瘤细胞表达，这些细胞反过来通过旁分泌作用吸引表达 CSF1 受体（CSF1R）的非肿瘤炎性细胞。
甲磺酸伊马替尼（IM）阻断 CSF1R，先前的病例报告表明，它也对 PVNS 具有抗肿瘤活性。作者进行了一项多机构回顾性研究，以评估 IM 在局部晚期/转移性 PVNS/TGCT 患者中的活性。
来自欧洲、澳大利亚和美国的 12 个机构的 29 名患者被纳入研究。其中 13 名男性，中位年龄为 41 岁，最常见的疾病部位是膝盖（n = 17；59%）。两名患者有肺和/或骨转移。27 名可评估患者中有 5 名（总体反应率为 19%；1 名完全缓解和 4 名部分缓解）有实体瘤反应评估（RECIST）反应，27 名患者中有 20 名（74%）疾病稳定。22 名可评估症状的患者中有 16 名（73%）出现症状改善。尽管有很高的症状改善率和良好的安全性，6 名患者因毒性而停药，4 名患者因不明医疗原因决定停止使用 IM。
IM 在 PVNS/TGCT 患者中显示出有趣的活性，为该疾病靶向 CSF1R 提供了概念验证。作者得出结论，必须平衡减轻局部 PVNS/TGCT 患者发病率的益处与慢性药物治疗的潜在毒性。
