紹介記事・論文

Phase I / IIa Trial of Autologous Formalin-fixed Tumor Vaccine Concomitant with Fractionated Radiotherapy for Initially-Diagnosed Glioblastoma

Authors: Yoshihiro Muragaki, Takashi Maruyama, Hiroshi Iseki, Masahiko Tanaka, Chie Shinohara, Kintomo Takakura, Koji Tsuboi, Tetsuya Yamamoto, Akira Matsumura, Masao Matsutani, Katsuyuki Karasawa, Katsunori Shimada, Naohito Yamaguchi, Yoichi Nakazato, Keiki Sato, Yoji Uemae, Tadao Ohno, and Tomokatsu Hori

Journal: J. NeuroSurgery, 2011, 115(2):248-55, (e-pub ahead, DOI: 10.3171/2011.4.JNS10377)

Abstract: The objective of the present study was analysis of results of the prospective clinical trial directed on the evaluation of therapeutic efficacy of the autologous formalin-fixed tumor vaccine (AFTV) concomitant with fractionated radiotherapy (FRT) in cases of initially-diagnosed glioblastoma multiforme (GBM). Twenty-four patients were enrolled into clinical trial, while 2 cases were excluded from the final analysis of results. The treatment protocol included aggressive surgical resection of the tumor, FRT up to the total dose of 60 Gy, and 3 concomitant courses of AFTV performed with an interval of one week at the late stage of irradiation. Two delayed type hypersensitivity tests were done, 48 hr before the initial course of vaccination (DTH-1) and two weeks after the third one (DTH-2). Defined primary endpoint was overall survival (OS), whereas secondary endpoints were progression-free survival (PFS) and safety of concomitant treatment. Median OS comprised 21.4 months (95% confidence interval: 13.8 - 31.3 months). The actuarial 2-years survival rate constituted 40%. Median PFS was 7.6 months (95% confidence interval: 4.3 - 13.6 months). PFS was significantly longer in cases with greater p53 staining index (P < 0.05) and larger size of DTH-2 response (P < 0.001). AFTV injection concomitant with FRT was well tolerated by all patients and in no one case treatment-related adverse effects exceeded grade 1 toxicity. In conclusion, the results of the present study demonstrate, that AFTV treatment concomitant with FRT may be beneficial for patients with initially-diagnosed GBM, therefore its efficacy should be tested in further clinical trials.