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Treatment
of Progressive or Recurrent Glioblastoma Multiforme in Adults with Herpes
Simplex Virus Thymidine Kinase Gene Vector-Producer Cells Followed by
Intravenous Ganciclovir Administration: A Phase I/II Multi-Institutional Trial
Michael
D. Prados1,
Michael
McDermott1,
Susan M.
Chang1,
Charles B.
Wilson1,
James Fick1’2,
Kenneth W.
Culver3’4,
John Van Gilder5, 6’1,
Alex Spence6,
Mitchel Berger6’1
1University
of California, San Francisco, CA, USA; 2Department of
Neurosurgery, The Medical College of Georgia, Augusta, Georgia, USA; 3Iowa Methodist Medical Center, Seattle, USA; 4Novartis Pharmaceuticals Corp., East Hanover, NJ, USA;
5University of Iowa Medical Center, Seattle, USA;
6University of Washington, Seattle, USA
To
determine the safety and evaluate the efficacy of repeated administration of
virus-producing cells (GLI 328) containing the herpes simplex virus
thymidine-kinase gene followed by ganciclovir treatment in adults with recurrent
glioblastoma multiforme, we conducted a phase I/II multi-institutional
trial.
Eligible patients underwent surgical resection of tumor, followed by injections
of vector producing cells (VPC) into the brain adjacent to the cavity.
An Ommaya reservoir placed after surgery was used to inject a further dose of
VPC seven days after surgery, followed seven days later by ganciclovir.
Further gene therapy was given at 28-day intervals for up to a total of five
cycles.
Toxicity and anti-tumor effect were assessed.
Of 30 patients who enrolled in the study, 16 experienced serious adverse events
possibly related to the experimental therapy.
Laboratory testing, including polymerase chain reaction analysis to detect
replication-competent retrovirus in peripheral blood lymphocytes and tissues, as
well as co-cultivation bioassays, were negative.
Before receiving ganciclovir, 37% of the patients showed evidence of transduced
peripheral blood leukocytes, but only 12% showed a persistence of transduced
cells at the end of the first cycle of ganciclovir.
Median survival was 8.4 months.
Twenty percent of the patients (n = 6) survived more than 12 months
from the date of study entry.
This treatment modality is feasible and appears to have some evidence of
efficacy.
Toxicity may be related in part to the method of gene delivery.
Keywords:
ganciclovir, gene therapy, glioblastoma multiforme, herpes virus, thymidine
kinase gene
Copyright
© 2003 Kluwer
Academic Publishers. All
rights reserved
Source: http://ipsapp009.kluweronline.com/content/getfile/5042/105/3/abstract.htm
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