PMID- 21968943
OWN - NLM
STAT- MEDLINE
DCOM- 20120521
LR  - 20211020
IS  - 1573-7373 (Electronic)
IS  - 0167-594X (Print)
IS  - 0167-594X (Linking)
VI  - 106
IP  - 3
DP  - 2012 Feb
TI  - A phase II study of O6-benzylguanine and temozolomide in pediatric patients with 
      recurrent or progressive high-grade gliomas and brainstem gliomas: a Pediatric 
      Brain Tumor Consortium study.
PG  - 643-9
LID - 10.1007/s11060-011-0709-z [doi]
AB  - To estimate the sustained (>/=8 weeks) objective response rate in pediatric 
      patients with recurrent or progressive high-grade gliomas (HGG, Stratum A) or 
      brainstem gliomas (BSG, Stratum B) treated with the combination of 
      O6-benzylguanine (O6BG) and temozolomide((R)) (TMZ). Patients received O6BG 120 
      mg/m(2)/d IV followed by TMZ 75 mg/m(2)/d orally daily for 5 consecutive days of 
      each 28-day course. The target objective response rate to consider the 
      combination active was 17%. A two-stage design was employed. Forty-three patients 
      were enrolled; 41 were evaluable for response, including 25 patients with HGG and 
      16 patients with BSG. The combination of O6BG and TMZ was tolerable, and the 
      primary toxicities were myelosuppression and gastrointestinal symptoms. One 
      sustained (>/=8 weeks) partial response was observed in the HGG cohort; no 
      sustained objective responses were observed in the BSG cohort. Long-term (>/=6 
      courses) stable disease (SD) was observed in 4 patients in Stratum A and 1 
      patient in Stratum B. Of the 5 patients with objective response or long-term SD, 
      3 underwent central review with 2 reclassified as low-grade gliomas. The 
      combination of O6BG and TMZ did not achieve the target response rate for activity 
      in pediatric patients with recurrent or progressive HGG and BSG.
FAU - Warren, Katherine E
AU  - Warren KE
AD  - Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA. 
      warrenk@mail.nih.gov
FAU - Gururangan, Sri
AU  - Gururangan S
FAU - Geyer, J Russell
AU  - Geyer JR
FAU - McLendon, Roger E
AU  - McLendon RE
FAU - Poussaint, Tina Young
AU  - Poussaint TY
FAU - Wallace, Dana
AU  - Wallace D
FAU - Balis, Frank M
AU  - Balis FM
FAU - Berg, Stacey L
AU  - Berg SL
FAU - Packer, Roger J
AU  - Packer RJ
FAU - Goldman, Stewart
AU  - Goldman S
FAU - Minturn, Jane E
AU  - Minturn JE
FAU - Pollack, Ian F
AU  - Pollack IF
FAU - Boyett, James M
AU  - Boyett JM
FAU - Kun, Larry E
AU  - Kun LE
LA  - eng
GR  - M01 RR000188/RR/NCRR NIH HHS/United States
GR  - U01 CA081457/CA/NCI NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
GR  - U01 CA81457/CA/NCI NIH HHS/United States
GR  - 5M01RR000188/RR/NCRR NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
DEP - 20111004
PL  - United States
TA  - J Neurooncol
JT  - Journal of neuro-oncology
JID - 8309335
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 01KC87F8FE (O(6)-benzylguanine)
RN  - 5Z93L87A1R (Guanine)
RN  - 7GR28W0FJI (Dacarbazine)
RN  - EC 2.1.1.- (DNA Modification Methylases)
RN  - EC 2.1.1.63 (MGMT protein, human)
RN  - EC 6.5.1.- (DNA Repair Enzymes)
RN  - YF1K15M17Y (Temozolomide)
SB  - IM
MH  - Adolescent
MH  - Antineoplastic Agents/*therapeutic use
MH  - Brain Stem Neoplasms/*drug therapy/mortality
MH  - Child
MH  - Child, Preschool
MH  - DNA Modification Methylases/metabolism
MH  - DNA Repair Enzymes/metabolism
MH  - Dacarbazine/*analogs & derivatives/therapeutic use
MH  - Drug Therapy, Combination/methods
MH  - Female
MH  - Glioma/*drug therapy/mortality
MH  - Guanine/*analogs & derivatives/therapeutic use
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Ki-67 Antigen/metabolism
MH  - Male
MH  - Proportional Hazards Models
MH  - Retrospective Studies
MH  - Temozolomide
MH  - Tumor Suppressor Proteins/metabolism
MH  - Young Adult
PMC - PMC3518022
MID - NIHMS422479
EDAT- 2011/10/05 06:00
MHDA- 2012/05/23 06:00
PMCR- 2012/12/10
CRDT- 2011/10/05 06:00
PHST- 2011/05/23 00:00 [received]
PHST- 2011/09/12 00:00 [accepted]
PHST- 2011/10/05 06:00 [entrez]
PHST- 2011/10/05 06:00 [pubmed]
PHST- 2012/05/23 06:00 [medline]
PHST- 2012/12/10 00:00 [pmc-release]
AID - 10.1007/s11060-011-0709-z [doi]
PST - ppublish
SO  - J Neurooncol. 2012 Feb;106(3):643-9. doi: 10.1007/s11060-011-0709-z. Epub 2011 
      Oct 4.