医学
2型神经纤维瘤病
耐受性
内科学
不利影响
血管内皮生长因子
临床终点
贝伐单抗
不良事件通用术语标准
外科
肿瘤科
胃肠病学
神经鞘瘤
化疗
血管内皮生长因子受体
临床试验
作者
Ryota Tamura,Yoshiharu Yamanobe,Masato Fujioka,Yukina Morimoto,Mariko Fukumura,Masato Nakaya,Yuji Oishi,Mizuto Sato,Ryo Ueda,Hiromi Fujiwara,Tetsuro Hikichi,Shinobu Noji,Naoki Oishi,Hiroyuki Ozawa,Kaoru Ogawa,Yutaka Kawakami,Takayuki Ohira,Kazunari Yoshida,Ryota Tamura
摘要
PURPOSE The humanized antivascular endothelial growth factor (VEGF) antibody bevacizumab (Bev) is efficacious for the treatment of NF2-related schwannomatosis (NF2), previously known as neurofibromatosis type 2. This study evaluated the safety and efficacy of a VEGF receptor (VEGFR) vaccine containing VEGFR1 and VEGFR2 peptides in patients with NF2 with progressive schwannomas (jRCTs031180184). MATERIALS AND METHODS VEGFR1 and VEGFR2 peptides were injected subcutaneously into infra-axillary and inguinal regions, once a week for 4 weeks and then once a month for 4 months. The primary end point was safety. Secondary end points included tolerability, hearing response, imaging response, and immunologic response. RESULTS Sixteen patients with NF2 with progressive schwannomas completed treatment and were assessed. No severe vaccine-related adverse events occurred. Among the 13 patients with assessable hearing, word recognition score improved in five patients at 6 months and two at 12 months. Progression of average hearing level of pure tone was 0.168 dB/mo during the year of treatment period, whereas long-term progression was 0.364 dB/mo. Among all 16 patients, a partial response was observed in more than one schwannoma in four (including one in which Bev had not been effective), minor response in 5, and stable disease in 4. Both VEGFR1-specific and VEGFR2-specific cytotoxic T lymphocytes (CTLs) were induced in 11 patients. Two years after vaccination, a radiologic response was achieved in nine of 20 assessable schwannomas. CONCLUSION This study demonstrated the safety and preliminary efficacy of VEGFR peptide vaccination in patients with NF2. Memory-induced CTLs after VEGFR vaccination may persistently suppress tumor progression.
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