Varker Kimberly A, Biber Jennifer E, Kefauver Cheryl, Jensen Rhonda, Lehman Amy, Young Donn, Wu Haifeng, Lesinski Gregory B, Kendra Kari, Chen Helen X, Walker Michael J, Carson William E
Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, N924 Doan Hall, 410 W 10th Avenue, Columbus, Ohio 43210, USA.
Ann Surg Oncol. 2007 Aug;14(8):2367-76. doi: 10.1245/s10434-007-9389-5. Epub 2007 May 30.
Vascular endothelial growth factor (VEGF) is a proangiogenic molecule produced by melanoma cells. We hypothesized that administration of bevacizumab (Bev), a monoclonal antibody that neutralizes VEGF, with low-dose interferon alfa-2b (IFN-alpha2b), an inhibitor of basic fibroblast growth factor (FGF), would lead to the regression of metastatic melanoma.
Patients with metastatic melanoma were randomized to receive Bev (15 mg/kg intravenously every 2 weeks) with or without low-dose IFN-alpha2b (1 MU/m2 subcutaneously daily). Patients exhibiting a clinical response or stable disease after 12 weeks were treated until disease progression.
Thirty-two patients (16 per arm) were accrued (18 male, 14 female; mean age 57.5 years). Both regimens were well tolerated. Six patients developed easily managed exacerbations of preexisting hypertension. Two patients developed grade 3 proteinuria that resolved after a treatment break. IFN-alpha2b therapy was associated with grade 1 to 2 constitutional symptoms. Arterial thromboembolic complications were observed in three patients (two mild myocardial infarctions, one transient ischemic attack), all of whom had risk factors. One patient (Bev plus IFN-alpha2b arm) had locally recurrent scalp disease that partially responded to therapy. Eight patients (five Bev, three Bev plus IFN-alpha2b) had prolonged disease stabilization (24 to 146 weeks). Plasma levels of VEGF and FGF did not correlate with any clinical parameter. The patient with the longest period of stable disease had the highest baseline VEGF and FGF.
Bev was well tolerated at this dose and prolonged disease stabilization was achieved in one-quarter of metastatic melanoma patients. Low-dose IFN-alpha2b did not augment the activity of Bev.
血管内皮生长因子（VEGF）是黑色素瘤细胞产生的一种促血管生成分子。我们假设，给予贝伐单抗（Bev）（一种中和VEGF的单克隆抗体）联合低剂量干扰素α-2b（IFN-α2b）（一种碱性成纤维细胞生长因子（FGF）抑制剂）会导致转移性黑色素瘤消退。
转移性黑色素瘤患者被随机分为接受Bev（每2周静脉注射15 mg/kg）联合或不联合低剂量IFN-α2b（每日皮下注射1 MU/m²）治疗。在12周后出现临床反应或疾病稳定的患者持续治疗直至疾病进展。
共纳入32例患者（每组16例）（男18例，女14例；平均年龄57.5岁）。两种治疗方案耐受性均良好。6例患者出现易于控制的原有高血压加重。2例患者出现3级蛋白尿，在治疗中断后缓解。IFN-α2b治疗与1至2级全身症状相关。3例患者观察到动脉血栓栓塞并发症（2例轻度心肌梗死，1例短暂性脑缺血发作），所有患者均有危险因素。1例患者（Bev加IFN-α2b组）头皮局部复发病灶对治疗有部分反应。8例患者（5例Bev组，3例Bev加IFN-α2b组）疾病稳定期延长（24至146周）。VEGF和FGF的血浆水平与任何临床参数均无相关性。疾病稳定期最长的患者基线VEGF和FGF水平最高。
该剂量的Bev耐受性良好，四分之一的转移性黑色素瘤患者实现了疾病稳定期延长。低剂量IFN-α2b并未增强Bev的活性。
