Early results positive for treating high-grade gliomas with virus-based therapy




An investigational virus-based therapy was safely given to patients with high-grade or recurrent gliomas in a phase I study, improving survival for some, investigators report.

Dr. Timothy Cloughesy

Dr. Timothy Cloughesy

In the phase I trial of Toca 511 (vocimagene amiretrorepvec) in combination with surgical resection, median overall survival was 13.6 months (95% confidence interval, 10.8-20.0) among all evaluable patients with high-grade glioblastoma (n = 43) and 14.4 months (95% CI, 11.3-32.3) for patients with first or second recurrence (n = 32), Dr. Timothy Cloughesy of the University of California, Los Angeles, and his associates reported (Sci Transl Med. 2016;8:1-11).

Investigators compared their data to those of external controls with glioblastoma at first and second recurrence treated with lomustine and saw an almost twofold improvement in overall survival (13.6 months vs. 7.1 months (hazard ratio, 0.45; P = .003).

Toca 511 dispatches a virus to rapidly dividing cancer cells, then delivers a gene encoding an enzyme that converts a nontoxic prodrug, Toca FC (extended-release 5-fluorocytosine), into its active form, 5-fluorouracil.

A virus infects the tumor and delivers an enzyme, which activates a chemotherapeutic prodrug. C. Bickel / Science Translational Medicine (2016)

A virus infects the tumor and delivers an enzyme, which activates a chemotherapeutic prodrug.

There were no treatment-related deaths, and there were fewer grade 3 adverse events, compared with the external lomustine control group.

“Recurrent HGG [high-grade glioblastoma] is associated with dismal clinical outcomes, and patients are in need of safe and more efficacious therapy. The nonlytic RRV [retroviral replicating vector] Toca 511 and an extended-release 5-FC [5-fluorocytosine] have the potential to fill this medical need,” the researchers said.

A randomized phase II/III trial in patients with recurrent glioblastoma and anaplastic astrocytoma is underway, they said.

This study was supported by the Accelerate Brain Cancer Cure Foundation, the National Brain Tumor Society, the American Brain Tumor Association, the Musela Foundation, Voices Against Brain Cancer, and the National Institute of Neurological Disorders and Stroke. Thirteen investigators reported serving in advisory roles, having ownership or stock interest in, or receiving financial compensation from multiple companies.

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