MacDonald G C, Rasamoelisolo M, Entwistle J, Cuthbert W, Kowalski M, Spearman Maureen A, Glover N
Viventia Biotech Inc., 147 Hamelin St., Winnipeg, MB, Canada R3T 3Z1.
Med Oncol. 2009;26(3):257-64. doi: 10.1007/s12032-008-9111-x. Epub 2008 Oct 28.
VB4-845 is a novel recombinant fusion protein that targets the epithelial cellular adhesion molecule (EpCAM). This initial clinical trial was conducted to determine the maximum tolerated dose of intratumoral injections in patients with advanced squamous cell carcinoma of the head and neck and to assess pharmacokinetics and immunogenicity. Twenty-four patients with advanced, recurrent squamous cell carcinoma of the head and neck received two cycles of five daily intratumoral VB4-845 injections of 20, 40, 80, 130, 200, or 280 microg. The maximum tolerated dose was established to be 280 microg administered daily for 5 days. Common adverse events were pain due to intratumoral injection and reversibly elevated liver enzymes. Of the 24 patients, 15 had detectable blood levels with a mean drug half-life of 4.0 +/- 0.3 h. VB4-845 reduced or stabilized tumors in 71.4% of epithelial cell adhesion molecule-positive patients. VB4-845 intratumoral injection therapy was well tolerated and feasible.
VB4-845是一种靶向上皮细胞粘附分子（EpCAM）的新型重组融合蛋白。开展这项初始临床试验的目的是确定晚期头颈部鳞状细胞癌患者瘤内注射的最大耐受剂量，并评估其药代动力学和免疫原性。24例晚期复发性头颈部鳞状细胞癌患者接受了两个疗程的治疗，每天进行5次瘤内注射VB4-845，剂量分别为20、40、80、130、200或280微克。确定的最大耐受剂量为每天280微克，连续给药5天。常见的不良事件是瘤内注射引起的疼痛和肝酶可逆性升高。24例患者中，15例可检测到血液中的药物水平，平均药物半衰期为4.0±0.3小时。在71.4%的上皮细胞粘附分子阳性患者中，VB4-845使肿瘤缩小或稳定。VB4-845瘤内注射治疗耐受性良好且可行。
