ASCO 2015: Glioblastoma Poliovirus Therapy Works Best at a Low Dosage

ASCO 2015: Glioblastoma Poliovirus Therapy Works Best at a Low Dosage

By The ASCO Post
Posted: 6/12/2015 11:30:26 AM
Last Updated: 6/12/2015 4:29:13 PM

  • This phase I trial worked to identify the optimal dose to minimize toxicity.
  • At the higher doses, inflammation at the tumor site increased the severity of side effects, including weakness and seizures; required prolonged steroid use; and dampened the immune response to the modified poliovirus.
  • The lower dosage minimizes side effects.

A modified poliovirus therapy that is showing activity in patients with glioblastoma works best at a low dosage, according to the research team at Duke’s Preston Robert Tisch Brain Tumor Center. The dosage findings for the first 20 patients in the phase 1 trial were presented June 1 at the 2015 ASCO Annual Meeting in Chicago (Abstract 2068).

“The purpose of a phase 1 trial is to identify the optimal dose to minimize toxicity,” said Annick Desjardins, MD, Director of Clinical Research at the Brain Tumor Center at the Duke Cancer Institute, and lead study author. “Our trial design included escalating to higher doses, which is what is done with chemotherapy.”

“For chemotherapy, we are trained to give the largest dose possible with acceptable toxicity, because that is how the drugs work to attack tumors,” Dr. Desjardins said. “But that does not appear to be necessary with our therapy, and in fact, a lower dose attacks the tumor as well—and results in fewer side effects.”

Dosage Modification

At the higher doses, Dr. Desjardins and colleagues reported inflammation at the tumor site increased the severity of side effects, including weakness and seizures. Patients required prolonged steroid use to reduce the inflammation, and the steroids dampened the immune response that the modified poliovirus is designed to initiate.

The research team has settled on a dose that is actually lower than the amount first tested, which the first study patient received in May 2012. That patient is still alive, and has no regrowth of her tumor. Five patients have been enrolled in the trial at the lower dosage level, designated as minus one.

“We are now keeping to minus one,” Dr. Desjardins said. “Inflammation is much better at this level, and that’s what we want.”

Study authors report that the therapy appears to be safe, with side effects related to localized brain inflammation: muscle weakness and paralysis, seizures, headaches, limb swelling and tingling, speech impairments, and headaches. Twelve of the first 20 patients treated remain alive, with the first and second patients more than 31 months post-treatment.

The median survival for patients with glioblastoma is 14.6 months, according to the American Brain Tumor Association.

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