Hashimoto Naoya, Tsuboi Akihiro, Kagawa Naoki, Chiba Yasuyoshi, Izumoto Shuichi, Kinoshita Manabu, Kijima Noriyuki, Oka Yoshihiro, Morimoto Soyoko, Nakajima Hiroko, Morita Satoshi, Sakamoto Junichi, Nishida Sumiyuki, Hosen Naoki, Oji Yusuke, Arita Norio, Yoshimine Toshiki, Sugiyama Haruo
Department of Neurosurgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan,
Cancer Immunol Immunother. 2015 Jun;64(6):707-16. doi: 10.1007/s00262-015-1674-8. Epub 2015 Mar 14.
To investigate the safety of combined Wilms tumor 1 peptide vaccination and temozolomide treatment of glioblastoma, a phase I clinical trial was designed. Seven patients with histological diagnosis of glioblastoma underwent concurrent radiotherapy and temozolomide therapy. Patients first received Wilms tumor 1 peptide vaccination 1 week after the end of combined concurrent radio/temozolomide therapy, and administration was continued once per week for 7 weeks. Temozolomide maintenance was started and performed for up to 24 cycles, and the observation period for safety encompassed 6 weeks from the first administration of maintenance temozolomide. All patients showed good tolerability during the observation period. Skin disorders, such as grade 1/2 injection-site reactions, were observed in all seven patients. Although grade 3 lymphocytopenia potentially due to concurrent radio/temozolomide therapy was observed in five patients (71.4 %), no other grade 3/4 hematological or neurological toxicities were observed. No autoimmune reactions were observed. All patients are still alive, and six are on Wilms tumor 1 peptide vaccination without progression, yielding a progression-free survival from histological diagnosis of 5.2-49.1 months. Wilms tumor 1 peptide vaccination was stopped in one patient after 12 injections by the patient's request. The safety profile of the combined Wilms tumor 1 peptide vaccination and temozolomide therapy approach for treating glioblastoma was confirmed.
为研究肾母细胞瘤1肽疫苗联合替莫唑胺治疗胶质母细胞瘤的安全性，设计了一项I期临床试验。7例经组织学诊断为胶质母细胞瘤的患者接受了同步放疗和替莫唑胺治疗。患者在同步放化疗结束后1周首次接受肾母细胞瘤1肽疫苗接种，每周给药1次，共7周。开始替莫唑胺维持治疗，最多进行24个周期，安全性观察期为首次给予维持替莫唑胺后的6周。所有患者在观察期内均表现出良好的耐受性。所有7例患者均观察到皮肤疾病，如1/2级注射部位反应。虽然5例患者（71.4%）观察到可能因同步放化疗导致的3级淋巴细胞减少，但未观察到其他3/4级血液学或神经毒性。未观察到自身免疫反应。所有患者均存活，6例患者仍在接受肾母细胞瘤1肽疫苗接种且无进展，从组织学诊断开始的无进展生存期为5.2 - 49.1个月。1例患者在接种12次后应患者要求停止了肾母细胞瘤1肽疫苗接种。证实了肾母细胞瘤1肽疫苗联合替莫唑胺治疗胶质母细胞瘤方法的安全性。
