Lindor N M, Dozois R, Nelson H, Wolff B, King J, Boardman L, Wilson M, Greene M H, Karnes W, Mesa R, Welch T, Edmonson J, Limburg P
Department of Medical Genetics, Mayo Clinic, Scottsdale, Arizona, USA.
Am J Gastroenterol. 2003 Aug;98(8):1868-74. doi: 10.1111/j.1572-0241.2003.07479.x.
Pirfenidone (Deskar, Marnac Inc., Dallas, TX), 5-methyl-1-phenyl-2-(1H)-pyridone, is a broad-spectrum, noncytotoxic, oral antifibrotic agent that is reported to inhibit or block the action of cytokine growth factors: transforming growth factor beta1, platelet-derived growth factor, epidermal growth factor, and fibroblast growth factor, and to prevent formation of new fibrotic lesions.
We enrolled 10 women and four men with extensive familial adenomatous polyposis (FAP)-associated desmoid disease in a 2-yr open-label treatment trial with oral pirfenidone. Imaging of desmoids was conducted at baseline and 6, 12, and 24 months.
No drug toxicity or drug intolerance was encountered. Seven patients dropped out (three because of progressive disease), and seven continued for at least 18 months. Of those that continued, two had partial but significant reduction in the size of all desmoids beginning in the first 6 months of treatment, and two others experienced relief of symptoms without change in desmoid size. Three patients experienced no change in tumor size or symptoms.
Pirfenidone is well tolerated by patients with FAP-associated desmoid tumors. Some patients with FAP/desmoid tumors treated with pirfenidone had regression of tumors, some had progression, and some had no response. Patients with rapidly growing tumors did not respond to pirfenidone. A placebo-controlled trial is needed to determine whether there is a subset of patients for whom pirfenidone may result in partial shrinkage of desmoid tumors, because the natural history of desmoid tumors is not predictable or understood.
吡非尼酮（商品名Deskar，Marnac公司，得克萨斯州达拉斯），即5-甲基-1-苯基-2-(1H)-吡啶酮，是一种广谱、无细胞毒性的口服抗纤维化药物，据报道它能抑制或阻断细胞因子生长因子的作用，包括转化生长因子β1、血小板衍生生长因子、表皮生长因子和成纤维细胞生长因子，并能防止新的纤维化病变形成。
我们招募了10名女性和4名男性患有广泛家族性腺瘤性息肉病（FAP）相关硬纤维瘤病的患者，进行了一项为期2年的口服吡非尼酮开放标签治疗试验。在基线以及第6、12和24个月对硬纤维瘤进行成像。
未出现药物毒性或药物不耐受情况。7名患者退出（3名因疾病进展），7名患者持续治疗至少18个月。在持续治疗的患者中，2名患者在治疗的前6个月开始所有硬纤维瘤的大小出现部分但显著缩小，另外2名患者症状缓解但硬纤维瘤大小未变。3名患者肿瘤大小和症状均无变化。
FAP相关硬纤维瘤肿瘤患者对吡非尼酮耐受性良好。一些接受吡非尼酮治疗的FAP/硬纤维瘤肿瘤患者肿瘤出现消退，一些患者病情进展，还有一些患者无反应。肿瘤快速生长的患者对吡非尼酮无反应。需要进行一项安慰剂对照试验，以确定是否有一部分患者使用吡非尼酮可能导致硬纤维瘤肿瘤部分缩小，因为硬纤维瘤肿瘤的自然病程不可预测或难以理解。
