PMID- 10933931
OWN - NLM
STAT- MEDLINE
DCOM- 20000906
LR  - 20231120
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 1
IP  - 2
DP  - 2000 Feb
TI  - Phase I study of adenoviral delivery of the HSV-tk gene and ganciclovir 
      administration in patients with current malignant brain tumors.
PG  - 195-203
AB  - Between December 1996 and September 1998, 13 patients with advanced recurrent 
      malignant brain tumors (9 with glioblastoma multiforme, 1 with gliosarcoma, and 3 
      with anaplastic astrocytoma) were treated with a single intratumoral injection of 
      2 x 10(9), 2 x 10(10), 2 x 10(11), or 2 x 10(12) vector particles (VP) of a 
      replication-defective adenoviral vector bearing the herpes simplex virus 
      thymidine kinase gene driven by the Rous sarcoma virus promoter (Adv.RSVtk), 
      followed by ganciclovir (GCV) treatment. The VP to infectious unit ratio was 
      20:1. Our primary objective was to determine the safety of this treatment. 
      Injection of Adv.RSVtk in doses <==2 x 10(11) VP, followed by GCV, was safely 
      tolerated. Patients treated with the highest dose, 2 x 10(12) VP, exhibited 
      central nervous system toxicity with confusion, hyponatremia, and seizures. One 
      patient is living and stable 29.2 months after treatment. Two patients survived 
      >25 months before succumbing to tumor progression. Ten patients died within 10 
      months of treatment, 9 from tumor progression and 1 with sepsis and endocarditis. 
      Neuropathologic examination of postmortem tissue demonstrated cavitation at the 
      injection site, intratumoral foci of coagulative necrosis, and variable 
      infiltration of the residual tumor with macrophages and lymphocytes.
FAU - Trask, T W
AU  - Trask TW
AD  - Department of Neurosurgery, Baylor College of Medicine, Houston, Texas 77030, 
      USA. ttrask@bcm.tmc.edu
FAU - Trask, R P
AU  - Trask RP
FAU - Aguilar-Cordova, E
AU  - Aguilar-Cordova E
FAU - Shine, H D
AU  - Shine HD
FAU - Wyde, P R
AU  - Wyde PR
FAU - Goodman, J C
AU  - Goodman JC
FAU - Hamilton, W J
AU  - Hamilton WJ
FAU - Rojas-Martinez, A
AU  - Rojas-Martinez A
FAU - Chen, S H
AU  - Chen SH
FAU - Woo, S L
AU  - Woo SL
FAU - Grossman, R G
AU  - Grossman RG
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Antiviral Agents)
RN  - EC 2.7.1.21 (Thymidine Kinase)
RN  - P9G3CKZ4P5 (Ganciclovir)
SB  - IM
MH  - Adenoviridae/*genetics/immunology
MH  - Adult
MH  - Aged
MH  - Antiviral Agents/administration & dosage/*pharmacology
MH  - Astrocytoma/genetics/mortality/therapy
MH  - Avian Sarcoma Viruses/genetics
MH  - Brain Neoplasms/diagnostic imaging/*genetics/mortality/*therapy
MH  - Combined Modality Therapy
MH  - Disease-Free Survival
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Ganciclovir/administration & dosage/*pharmacology
MH  - *Genetic Therapy
MH  - Genetic Vectors/administration & dosage
MH  - Glioblastoma/diagnostic imaging/genetics/mortality/therapy
MH  - Gliosarcoma/genetics/mortality/therapy
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Promoter Regions, Genetic
MH  - Radiography
MH  - Simplexvirus/*enzymology
MH  - Thymidine Kinase/*genetics
MH  - Time Factors
MH  - Treatment Outcome
EDAT- 2000/08/10 11:00
MHDA- 2000/09/09 11:01
CRDT- 2000/08/10 11:00
PHST- 2000/08/10 11:00 [pubmed]
PHST- 2000/09/09 11:01 [medline]
PHST- 2000/08/10 11:00 [entrez]
AID - S1525-0016(00)90030-3 [pii]
AID - 10.1006/mthe.2000.0030 [doi]
PST - ppublish
SO  - Mol Ther. 2000 Feb;1(2):195-203. doi: 10.1006/mthe.2000.0030.