Literature DB >> 21568657

Phase I/IIa trial of autologous formalin-fixed tumor vaccine concomitant with fractionated radiotherapy for newly diagnosed glioblastoma. Clinical article.

Yoshihiro Muragaki1, 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, Youji Uemae, Tadao Ohno, Yoshikazu Okada, Tomokatsu Hori.   

Abstract

OBJECT: The objective of the present study was analysis of results of the prospective clinical trial directed toward the evaluation of therapeutic efficacy of the administration of autologous formalin-fixed tumor vaccine (AFTV) concomitant with fractionated radiotherapy in cases of newly diagnosed glioblastoma multiforme.
METHODS: Twenty-four patients were enrolled into the clinical trial, while 2 cases were excluded from the final analysis of results. The treatment protocol included aggressive tumor resection, fractionated radiotherapy up to a total dose of 60 Gy, and 3 concomitant courses of AFTV administered with an interval of one week at the late stage of irradiation. Two delayed-type hypersensitivity (DTH) tests were done--one 48 hours before the initial course of vaccination (DTH-1) and one 2 weeks after the third (DTH-2). All but one of the patients received salvage therapy at the time of tumor progression. The defined primary end point was overall survival; secondary end points were progression-free survival and safety of concomitant treatment.
RESULTS: The median duration of overall survival was 19.8 [corrected] months (95% CI 13.8-31.3 months). The actuarial 2-year survival rate was 40%. The median duration of progression-free survival was 7.6 months (95% CI 4.3-13.6 months). Overall survival showed a statistically significant association with recursive partitioning analysis class (p < 0.05); progression-free survival showed a statistically significant association with p53 staining index (p < 0.05) and size of DTH-2 response (p < 0.001). AFTV injection concomitant with fractionated radiotherapy was well tolerated by all patients and in no case did treatment-related adverse effects exceed Grade 1 toxicity; adverse effects were limited to local erythema, induration, and swelling at the site of injection.
CONCLUSIONS: The results of this study demonstrate that AFTV treatment concomitant with fractionated radiotherapy may be effective in patients with newly diagnosed glioblastoma. Further clinical testing is warranted.

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Year:  2011        PMID: 21568657     DOI: 10.3171/2011.4.JNS10377

Source DB:  PubMed          Journal:  J Neurosurg        ISSN: 0022-3085            Impact factor:   5.115


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