PMID- 24995786
OWN - NLM
STAT- MEDLINE
DCOM- 20141118
LR  - 20230413
IS  - 1933-0693 (Electronic)
IS  - 0022-3085 (Linking)
VI  - 121
IP  - 3
DP  - 2014 Sep
TI  - Phase I/IIa trial of fractionated radiotherapy, temozolomide, and autologous 
      formalin-fixed tumor vaccine for newly diagnosed glioblastoma.
PG  - 543-53
LID - 10.3171/2014.5.JNS132392 [doi]
AB  - OBJECT: Temozolomide (TMZ) may enhance antitumor immunity in patients with 
      glioblastoma multiforme (GBM). In this paper the authors report on a prospective 
      Phase I/IIa clinical trial of fractionated radiotherapy (FRT) concomitant with 
      TMZ therapy, followed by treatment with autologous formalin-fixed tumor vaccine 
      (AFTV) and TMZ maintenance in patients with newly diagnosed GBM. METHODS: 
      Twenty-four patients (age 16-75 years, Karnofsky Performance Scale score >/= 60% 
      before initiation of FRT) with newly diagnosed GBM received a total dose of 60 Gy 
      of FRT with daily concurrent TMZ. After a 4-week interval, the patients received 
      3 AFTV injections and the first course of TMZ maintenance chemotherapy for 5 
      days, followed by multiple courses of TMZ for 5 days in each 28-day cycle. 
      RESULTS: This treatment regimen was well tolerated by all patients. The 
      percentage of patients with progression-free survival (PFS) >/= 24 months was 33%. 
      The median PFS, median overall survival (OS), and the actuarial 2- and 3-year 
      survival rates of the 24 patients were 8.2 months, 22.2 months, 47%, and 38%, 
      respectively. The median PFS in patients with a delayed-type hypersensitivity 
      (DTH) response after the third AFTV injection (DTH-2) of 10 mm or larger 
      surpassed the median length of follow-up for progression-free patients (29.5 
      months), which was significantly greater than the median PFS in patients with a 
      smaller DTH-2 response. CONCLUSIONS: The treatment regimen was well tolerated and 
      resulted in favorable PFS and OS for newly diagnosed GBM patients. Clinical trial 
      registration no.: UMIN000001426 (UMIN clinical trials registry, Japan).
FAU - Ishikawa, Eiichi
AU  - Ishikawa E
AD  - Department of Neurosurgery, Faculty of Medicine.
FAU - Muragaki, Yoshihiro
AU  - Muragaki Y
FAU - Yamamoto, Tetsuya
AU  - Yamamoto T
FAU - Maruyama, Takashi
AU  - Maruyama T
FAU - Tsuboi, Koji
AU  - Tsuboi K
FAU - Ikuta, Soko
AU  - Ikuta S
FAU - Hashimoto, Koichi
AU  - Hashimoto K
FAU - Uemae, Youji
AU  - Uemae Y
FAU - Ishihara, Takeshi
AU  - Ishihara T
FAU - Matsuda, Masahide
AU  - Matsuda M
FAU - Matsutani, Masao
AU  - Matsutani M
FAU - Karasawa, Katsuyuki
AU  - Karasawa K
FAU - Nakazato, Yoichi
AU  - Nakazato Y
FAU - Abe, Tatsuya
AU  - Abe T
FAU - Ohno, Tadao
AU  - Ohno T
FAU - Matsumura, Akira
AU  - Matsumura A
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140704
PL  - United States
TA  - J Neurosurg
JT  - Journal of neurosurgery
JID - 0253357
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 0 (Cancer Vaccines)
RN  - 7GR28W0FJI (Dacarbazine)
RN  - YF1K15M17Y (Temozolomide)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents, Alkylating/*therapeutic use
MH  - Brain Neoplasms/mortality/*therapy
MH  - Cancer Vaccines/*therapeutic use
MH  - Combined Modality Therapy
MH  - Dacarbazine/*analogs & derivatives/therapeutic use
MH  - Disease-Free Survival
MH  - Dose Fractionation, Radiation
MH  - Follow-Up Studies
MH  - Glioblastoma/mortality/*therapy
MH  - Humans
MH  - Japan
MH  - Male
MH  - Middle Aged
MH  - Prospective Studies
MH  - Radiotherapy/*methods
MH  - Survival Rate
MH  - Temozolomide
MH  - Treatment Outcome
MH  - Young Adult
OTO - NOTNLM
OT  - AFTV = autologous formalin-fixed tumor vaccine
OT  - CREIL Center = Critical Path Research and Education Integrated Leading
OT  - CTCAE = Common Terminology Criteria for Adverse Events
OT  - DTH = delayed-type hypersensitivity
OT  - FRT = fractionated radiotherapy
OT  - GBM = glioblastoma multiforme
OT  - IDH1 = isocitrate dehydrogenase-1
OT  - JBTRC = Japan Brain Tumor Reference Center
OT  - KPS = Karnofsky Performance Scale
OT  - MGMT = O6-methylguanine-DNA methyltransferase
OT  - MHC = major histocompatibility complex
OT  - MRC = Medical Research Council
OT  - OS = overall survival
OT  - PFS = progression-free survival
OT  - RPA = recursive partitioning analysis
OT  - TMZ = temozolomide
OT  - autologous formalin-fixed tumor vaccine
OT  - brain tumor immunotherapy
OT  - clinical trial
OT  - glioblastoma
OT  - oncology
OT  - temozolomide
EDAT- 2014/07/06 06:00
MHDA- 2014/11/19 06:00
CRDT- 2014/07/05 06:00
PHST- 2014/07/05 06:00 [entrez]
PHST- 2014/07/06 06:00 [pubmed]
PHST- 2014/11/19 06:00 [medline]
AID - 10.3171/2014.5.JNS132392 [doi]
PST - ppublish
SO  - J Neurosurg. 2014 Sep;121(3):543-53. doi: 10.3171/2014.5.JNS132392. Epub 2014 Jul 
      4.