As the most malignant of primary brain cancers, glioblastomas are frustratingly difficult to treat. Surgery is often risky and cannot remove all of the tumor, and chemotherapy eventually becomes ineffective for most patients. Median survival is around 15 months for patients with this tumor, and the quality of life in the last five months is often quite poor.
Houston Methodist Neurological Institute neurosurgeon David Baskin, M.D., is presenting preliminary data from a phase II clinical trial that suggests gene therapy, (AdV-Tk therapy), which uses a mediated herpes simplex virus, combined with a traditional treatment -- surgical resection -- could benefit glioblastoma patients with the worst prognoses.
From 2006 to 2010, 48 patients completed the experimental therapy. Their outcomes were compared to 134 patients who received surgical resection but no AdV-Tk therapy. While median survival increased 3.6 months (13.5 to 17.1 months), there was a 27 percent increase in overall survival at the end of five years. Baskin says that the data showed a dramatic improvement in survival for patients who underwent aggressive surgical excision, improving from 57 to 67 percent survival at 1 year, 22 to 35 percent at 2 years, and 8 to 19 percent at 3 years, with an overall improved survival of about eight months. Baskin says that "these results are far better that what we can now achieve with our present standard of care for treatment of patients with glioblastoma."
Patients participating in the multicenter, open-label phase II study had no prior radiation treatment and were deemed surgery candidates. During resection, neurosurgeons removed as much cancerous tissue as possible, then injected the AdV-Tk mixture 10 times at the site of resection. Patients were orally administered the antiviral drug valacylovir for two weeks following the procedure, and received radiation therapy and subsequent chemotherapy as tolerated.
Because of AdV-Tk's action, it is also called gene-mediated cytotoxic immunotherapy, or GMCI. The drug is designed to attack the cancer in several ways. First, it kills a number of cancer cells directly. It then releases specific proteins that cause a kind of superstimulation of the body's own immune system. This then activates a number of immune pathways much like a vaccine does, so that the immune system can then go on to kill many more cancer cells, for months to years later.
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