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AdV-tk Plus Valacyclovir Safe in New Malignant Gliomas

Last Updated: August 17, 2011.

The administration of an adenoviral vector containing the herpes simplex virus thymidine kinase gene, plus valacyclovir, is safe and can be delivered with surgery and accelerated radiation in patients with newly diagnosed malignant gliomas, according to a study published online Aug. 15 in the Journal of Clinical Oncology.

WEDNESDAY, Aug. 17 (HealthDay News) -- The administration of an adenoviral vector containing the herpes simplex virus thymidine kinase gene (AdV-tk), plus valacyclovir, is safe and can be delivered with surgery and accelerated radiation in patients with newly diagnosed malignant gliomas, according to a study published online Aug. 15 in the Journal of Clinical Oncology.

E. Antonio Chiocca, M.D., Ph.D., from the Ohio State University Medical Center in Columbus, and colleagues examined the safety of AdV-tk plus valacyclovir in up-front disease in combination with surgery and radiation, in patients with newly diagnosed malignant glioma. Between 2005 and 2007, 12 patients completed therapy with AdV-tk at 3×1010 (three patients), 1×1011 (three patients), and 3×1011 (six patients) vector particles via tumor bed injection at the time of surgery, and then 14 days of valacyclovir. To overlap with AdV-tk activity, radiation was initiated within nine days after injection. After valacyclovir treatment was completed, temozolamide was administered.

The investigators found no dose-limiting or significant added toxicities. Survival at two and three years was 33 and 25 percent, respectively. As assessed with the Functional Assessment of Cancer Therapy-Brain Stable, patients reported stable or improved quality of life after treatment. The tumors analyzed after treatment showed a significant CD3+ T-cell infiltrate. Three patients with O6-methylguanine-DNA methyltransferase unmethylated glioblastoma multiforme survived 6.5, 8.7, and 46.4 months.

"AdV-tk plus valacyclovir can be safely delivered with surgery and accelerated radiation in newly diagnosed malignant gliomas," the authors write.

Several authors disclosed financial ties to Advantagene, which is developing AdV-tk.

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