PMID- 20173548
OWN - NLM
STAT- MEDLINE
DCOM- 20100512
LR  - 20181201
IS  - 1524-4040 (Electronic)
IS  - 0148-396X (Linking)
VI  - 66
IP  - 3
DP  - 2010 Mar
TI  - Combination of intracranial temozolomide with intracranial carmustine improves 
      survival when compared with either treatment alone in a rodent glioma model.
PG  - 530-7; discussion 537
LID - 10.1227/01.NEU.0000365263.14725.39 [doi]
AB  - BACKGROUND: Local delivery of temozolomide (TMZ) through polymers is superior to 
      oral administration in a rodent glioma model. OBJECTIVE: We hypothesized that the 
      observed clinical synergy of orally administered TMZ and carmustine (BCNU) wafers 
      would translate into even greater effectiveness with the local delivery of BCNU 
      and TMZ and the addition of radiotherapy in animal models of malignant glioma. 
      METHODS: TMZ and BCNU were incorporated into biodegradable polymers that were 
      implanted in F344 rats bearing established intracranial tumors. We used 2 
      different rodent glioma models: the 9L gliosarcoma and the F98 glioma. RESULTS: 
      In the 9L rodent glioma model, groups treated with the combination of local TMZ, 
      local BCNU, and radiation therapy (XRT) had 75% long-term survivors (defined as 
      animals alive 120 days after tumor implantation), which was superior to the 
      combination of local TMZ and local BCNU (median survival, 95 days; long-term 
      survival, 25%) and the combination of oral TMZ, local BCNU, and XRT (median 
      survival, 62 days; long-term survival, 12.5%). To simulate the effect of this 
      treatment in chemoresistant gliomas, a second rodent model was used with the F98 
      glioma, a cell line relatively resistant to alkylating agents. F98 glioma cells 
      express high levels of alkyltransferase, an enzyme that deactivates alkylating 
      agents and is the major mechanism of resistance of gliomas. The triple therapy 
      showed a significant improvement in survival when compared with controls (P = 
      .0004), BCNU (P = .0043), oral TMZ (P = .0026), local TMZ (P = .0105), and the 
      combinations of either BCNU and XRT (P = .0378) or oral TMZ and BCNU (P = .0154). 
      CONCLUSION: The survival of tumor-bearing animals in the 9L and F98 glioma models 
      was improved with the local delivery of BCNU and TMZ combined with XRT when 
      compared with either treatment alone or oral TMZ, local BCNU, and XRT.
FAU - Recinos, Violette Renard
AU  - Recinos VR
AD  - Department of Neurosurgery, Johns Hopkins University School of Medicine, 
      Baltimore, Maryland, USA.
FAU - Tyler, Betty M
AU  - Tyler BM
FAU - Bekelis, Kimon
AU  - Bekelis K
FAU - Sunshine, Sarah Brem
AU  - Sunshine SB
FAU - Vellimana, Ananth
AU  - Vellimana A
FAU - Li, Khan Wayne
AU  - Li KW
FAU - Brem, Henry
AU  - Brem H
LA  - eng
GR  - CA62474/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neurosurgery
JT  - Neurosurgery
JID - 7802914
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 7GR28W0FJI (Dacarbazine)
RN  - U68WG3173Y (Carmustine)
RN  - YF1K15M17Y (Temozolomide)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Alkylating/*therapeutic use
MH  - Brain Neoplasms/*drug therapy/*mortality
MH  - Carmustine/*therapeutic use
MH  - Dacarbazine/*analogs & derivatives/therapeutic use
MH  - Disease Models, Animal
MH  - Drug Administration Routes
MH  - Drug Therapy, Combination/methods
MH  - Female
MH  - Glioma/*drug therapy/*mortality
MH  - Rats
MH  - Rats, Inbred F344
MH  - Survival Analysis
MH  - Temozolomide
MH  - Xenograft Model Antitumor Assays
EDAT- 2010/02/23 06:00
MHDA- 2010/05/13 06:00
CRDT- 2010/02/23 06:00
PHST- 2010/02/23 06:00 [entrez]
PHST- 2010/02/23 06:00 [pubmed]
PHST- 2010/05/13 06:00 [medline]
AID - 00006123-201003000-00014 [pii]
AID - 10.1227/01.NEU.0000365263.14725.39 [doi]
PST - ppublish
SO  - Neurosurgery. 2010 Mar;66(3):530-7; discussion 537. doi: 
      10.1227/01.NEU.0000365263.14725.39.