29 Apr Using Polio to Cure Brain Cancer: Clinical Trials
Most people remember polio as the scourge that paralyzed millions of children until a vaccine was developed in the 1950s. But in recent years, it has been resurrected as a potential treatment for deadly brain cancers.
Researchers at Duke University ran a Phase I* trial by injecting a modified poliovirus directly into deadly brain tumors. In the early stages, Duke doctors warned that it was impossible to predict how effective the polio treatment would be in a wider population, but they did see some success.
According to The Preston Robert Tisch Brain Tumor Center at Duke Cancer Institute, overall survival among patients reached 21% at 24 to 36 months and appeared to last for up to five years.
This is encouraging considering that patients with recurrent malignant glioblastoma, one of the most aggressive primary brain tumors, have an average survival rate of around 12–18 months, with only around 5 percent of patients living more than five years. Statistics have not changed much since the 1980s.
- Massachusetts General Hospital
- University Hospitals in Cleveland
- University Hospitals Seidman Cancer Center
Glioblastoma Polio Clinical Trials
Glioblastoma is among the deadliest of human cancers. On March 29, 2015, it was at the center of a two-part 60 Minutes report that was 10 months in the making.
Glioblastomas (GBM) are tumors that arise from astrocytes—the star-shaped cells that make up the “glue-like,” or supportive tissue of the brain. These tumors are usually highly malignant (cancerous) because the cells reproduce quickly and are supported by a large network of blood vessels. This tumor type represents about 17% of all primary brain tumors and about 75% of all astrocytomas. They increase in frequency with age, and affect more men than women. Only three percent of childhood brain tumors are glioblastomas. Patients who hit the three-year mark are generally considered ‘long-term’ survivors.
According to a summary of the 60 Minutes segment:
Every once in a while, a story comes through 60 Minutes that has the potential to change lives. Scott Pelley’s report on a new medical treatment using the poliovirus to kill cancer is that kind of story.
Dr. Arno Fried is on the Medical Advisory Committee of virtualtrials.com, a repository of all brain tumor trials. He is well-informed of all studies being conducted using viruses to ‘infect’ brain tumors and has served on the same virtualtrials.com committee with Dr. Allan H. Friedman, one of the main researchers involved in the Duke clinical trial that was the subject of the 60 Minutes segment. Dr. Friedman was extensively interviewed during the broadcast.
According to Dr. Fried, “I have long said that while there are some forms of brain cancer we can cure with surgery and chemotherapy (such as medullastoma in children, which has advanced to an 80 percent cure rate). However, for some forms of brain cancer, such as glioblastoma, we have not made any significant progress. The results today are the same as 50 years ago. Even before this study appeared, I believed that one day we will not be cutting out glioblastoma, which only buys the patients a limited amount of time. I have always said we’ll be injecting something into the tumor to kill it.”
“On average, we see a case a week of glioblastoma. While the majority are adults in their mid-20s to 50s, there are also children. In total, our practice probably treats 30 of these tumors a year, and has done so for the past two decades.”
“The concept of jump-starting the immune system is not new. It has been tried with both success and failure. Most notably, it has been very successful for melanoma,” says Dr. Fried.
According to the Duke study’s website: PVS-RIPO is a genetically engineered poliovirus that is being investigated as a new anti-cancer agent at the Preston Robert Tisch Brain Tumor Center at Duke. The idea of targeting cancer with viruses has been around for at least 100 years. However, valid strategies of using ‘oncolytic’ (cancer-fighting) viruses emerged only recently. This is mostly due to technological advances in genetic engineering of viruses.
This is an explanation from the website on how this works: PVS-RIPO is infused directly into a patients’ tumor (e.g. in the brain). This assures that the maximal amount of virus is delivered directly to the tumor. Once inside the tumor, PVS-RIPO infects and kills tumor cells. Although this tumor cell killing alone may have tumor-fighting results, the likely key to therapy with PVS-RIPO is its ability to recruit the patients’ immune response against the cancer. There are many events following PVS-RIPO infusion into the tumor that can contribute to such an outcome. The human immune system is trained to recognize virus infections and, thus, responds vigorously to the infected tumor. Unraveling why and how the immune system attacks tu”mors that were infused with PVS-RIPO is a major research goal of Dr. Matthias Gromeier of the Duke Neurosurgery Lab.
What is particularly remarkable is patients are in remission, with no signs of their tumor, in this study, which is only in a Phase 1 clinical trial. However, in order for it to be approved and instituted, it must go through Phase 1, 2, 3 clinical trials. “It has to be proven 1. safe, 2. effective and 3. better than what we currently have,” says Dr. Fried.
Dr. Fried knows first-hand the immediacy of finding results for glioblastomas.
“I have sent patients to Duke over the years; Duke has been at the forefront. Our practice has a handful of survivors of this type of brain tumor. I’d like to say we do great surgery; we do aggressive surgery. They had some additional therapy that prolonged life. One patient seems to be cured, a man in his 60s. He has been in remission for 15 years. A handful of others have been in remission 5 to 6 years.”
Dr. Fried concludes, “This is a major turning point in the treatment of glioblastoma and also cancer in general. If you can apply this technique to other cancers, we can take cancer in another direction. We’ve made advances in surgery radiation, such as the gamma knife. But if this pans out, it’s a major development.”
After Phase I and II clinical trials of PVS-RIPO against recurrent glioblastoma brain tumors, the plan is to extend these studies (Phases III) in a quest to establish PVS-RIPO as a possible therapy for brain tumors. In addition, PVS-RIPO has the potential to work for other types of cancers. The reason for this is that the mechanisms responsible for PVS-RIPO’s effects against brain tumors broadly apply to almost all cancers.
*Clinical trials are conducted in a series of steps, called phases – each phase is designed to answer a separate research question. A Phase 1 trial is to test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects. Updated 2021, from 2015.