AP-HP Department of Dermatology, Hôpital Saint-Louis, Universite Paris 7 Denis Diderot, Paris, France.
Clin Cancer Res. 2010 Jun 15;16(12):3288-95. doi: 10.1158/1078-0432.CCR-09-3401. Epub 2010 May 3.
The treatment of dermatofibrosarcoma protuberans (DFSP) involves wide local excision with frequent need for reconstructive surgery. A t(17;22) translocation resulting in COL1A1-PDGFB fusion is present in >95% of cases. Certain patient observations and a report on nine patients suggest that imatinib mesylate, targeting platelet-derived growth factor receptor beta, has clinical potential in DFSP. The primary aim of this phase II multicenter study was to define the percentage of clinical responders (Response Evaluation Criteria in Solid Tumors) to a 2-month preoperative daily administration of 600 mg of imatinib mesylate before wide local excision. The secondary aims were to determine tolerance, objective response from imaging results (ultrasound and magnetic resonance imaging), and pathologic responses observed in sequential tissue specimens.
A two-stage flexible design was used with interim analysis after the recruitment of six patients. Twenty-five adults suffering from primary or recurrent DFSP were included from July 2004 to May 2006.
The COL1A1-PDGFB fusion gene was detected in 21 out of 25 patients following fluorescence in situ hybridization analysis (two cases were noninformative). A clinical response was achieved in nine (36%) patients (95% confidence interval, 18.9-57.5). The median relative tumoral decrease was 20.0% (range, -12.5 to 100). Apart from expected grade 1 or 2 side effects, we observed one grade 3 neutropenia, one grade 3 maculopapular rash, and one grade 4 transient transaminitis.
Our results support the use of imatinib in a neoadjuvant setting in nonresectable DFSP, or when surgery is difficult or mutilating. These results will be useful for setting hypotheses in the evaluation of new drugs to treat primary or secondary resistance to imatinib.
隆突性皮肤纤维肉瘤（DFSP）的治疗需要广泛局部切除，经常需要重建手术。超过 95%的病例存在 COL1A1-PDGFB 融合的 t(17;22)易位。某些患者观察结果和对 9 例患者的报告表明，针对血小板衍生生长因子受体β的甲磺酸伊马替尼具有 DFSP 的临床潜力。这项 II 期多中心研究的主要目的是定义广泛局部切除前 2 个月每天服用 600mg 甲磺酸伊马替尼术前治疗的临床反应者（实体瘤反应评估标准）的百分比。次要目的是确定耐受性、影像学结果（超声和磁共振成像）的客观反应以及连续组织标本中观察到的病理反应。
采用两阶段灵活设计，在招募 6 例患者后进行中期分析。2004 年 7 月至 2006 年 5 月期间，共纳入 25 例原发性或复发性 DFSP 成人患者。
荧光原位杂交分析显示 25 例患者中有 21 例检测到 COL1A1-PDGFB 融合基因（两例结果不可用）。9 例（36%）患者达到临床反应（95%置信区间，18.9-57.5）。中位相对肿瘤缩小率为 20.0%（范围，-12.5 至 100）。除了预期的 1 或 2 级副作用外，我们还观察到 1 例 3 级中性粒细胞减少症、1 例 3 级斑丘疹、1 例 4 级短暂性转氨酶升高。
我们的结果支持在不可切除的 DFSP 或手术困难或致残时使用伊马替尼进行新辅助治疗。这些结果将有助于在评估治疗原发性或继发性伊马替尼耐药的新药时提出假设。
