“For chemotherapy, we are trained to give the largest dose possible
with acceptable toxicity, because that is how the drugs work to attack
tumors,” 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.”
At the higher doses, Desjardins and colleagues report, inflammation
at the tumor site increased the severity of side effects, including
weakness and seizures. Patients required prolonged steroid use to reduce
the inflammation, but this also 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,” 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, including 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 glioblastoma patients is 14.6 months, according to the American Brain Tumor Association.