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Israeli therapy kills brain cancer cells with electrical fields

Posted By David Brinn On June 10, 2007 @ 11:30 am In | No Comments

Patients carry the Novo-TTF device in a specialized over-the-shoulder bag and receive continuous treatment without changing their daily routine.An Israeli-developed treatment that specifically targets rapidly growing cancer cells with electrical fields shows great promise in treating patients with brain cancer.
The Novo-TTF (Tumor-Treating Fields) device, invented by Technion Professor emeritus Yoram Palti, uses electrical fields to disrupt tumor growth by interfering with cell division of cancerous cells, causing them to stop proliferating and die off instead of dividing and growing. Healthy brain cells rarely divide and have different electrical properties than cancerous brain cells. This allows the device to target cancer cells without affecting the healthy cells.

Early results of cell culture, animal and early phase human trials showed that compared to historical data, the device more than doubled the median overall survival rates in patients with recurrent glioblastoma multiforme (GBM), the most common and aggressive type of malignant brain tumor. The findings were reported in the Proceedings of the National Academy of Sciences (PNAS) journal article.

Palti, MD, Ph.D, founded a company NovoCure in 2000 to develop his research in treating cancer with electrical fields. According to Palti, this is the first time that electrical fields are being used to kill cancer cells, and it opens the door for other forms of cancer to be treated as well.

“This is a new general modality for treating cancer. In a way it’s similar to radiation, it’s physical in the same sense, but the major difference is that there are no side effects,” he told ISRAEL21c from his office at Novocure’s headquarters in Haifa.

“This trial showed a big change, and on the basis of these results, the FDA has approved going on to bigger trials. So far, at least in the lab, all types of tumors have been sensitive to the treatment, so we’re hopeful that it can treat all forms of cancer,” he added.

The single-arm, pilot trial of the safety and efficacy of the Novo-TTF treatment was performed on 10 patients for a total of 280 weeks. Efficacy analysis was performed for 10 recurrent GBM patients by comparing time to tumor progression (TTP), progression-free survival (PFS) at six months and overall survival (OS) in recurrent GBM patients to these endpoints in historical data.

“The median time for the cancer to recur after chemotherapy is around 10 weeks, and the overall survival rate is less than six months. In our trials, we’ve more than doubled those two parameters,” said Palti.

The electrical fields are delivered by means of insulated electrodes applied to the surface of the scalp. The electrodes look like bandages with wires attached. The device is powered by a small lightweight battery pack. Patients carry the Novo-TTF device in a specialized over-the-shoulder bag and receive continuous treatment without changing their daily routine.

“The novel mechanism of action of the Novo-TTF relies on the physical properties of the cancer cells, their shape and size, rather than the chemical make-up. We believe that this distinction enables the device to stop local proliferation and metastasis of cancer, which would explain the efficacy observed in these early findings,” said Dr. Elion Kirson lead author and vice president of R&D, NovoCure.

Based on the positive early findings, patient enrollment has begun for a large-scale phase III clinical trial to further clarify the efficacy and safety of the Novo-TTF in the treatment of recurrent GBM. The research is being conducted at 12 leading cancer centers across the United States, and eight centers in Europe.

According to Dr. Lara Kunschner, principal investigator for the study at Allegheny General Hospital’s Allegheny Singer Research Institute in Pittsburgh, patients with GBM usually have surgery to remove as much of the tumor as possible, followed by radiation, chemotherapy or a combination of both.

Overall, the median survival rate is about one year after diagnosis, she said, though younger people, those with few neurological impairments and those who have virtually all of the tumor surgically removed tend to live longer. While a few patients survive for long periods, a majority die or have a recurrence of the cancer within two years, she told the Pittsburgh Post Gazette.

Besides Allegheny General, other US centers currently recruiting patients for the Phase III trials include the University of Illinois at Chicago, which treated the first US patient with the device in the current study; Northwestern University; the New Jersey Neuroscience Institute; Memorial Sloan-Kettering Cancer Center; Columbia University Medical Center; the Cleveland Clinic; the University of Virginia Health System and the Medical College of Wisconsin.

The University of Pittsburgh Medical Center also plans to join the study soon along with a number of other centers.

The only patient currently enrolled at the Alleghany trial is Dennis Gibbons, 56, of Chartiers Township, who learned that he had brain cancer in 2004. An MRI indicated that he had a tumor about the size of a hen’s egg in the left frontal lobe of his brain. He had surgery to remove it that July, followed by radiation and chemotherapy.

But he had been told that the cancer would likely recur, and a biopsy last August indicated that it had come back. Kunschner mentioned the NovoCure trial, and Gibbons and his family volunteered for it.

“When you get to this point, you don’t know what’s going to work,” Gibbons’ wife, Leona told the Post Gazette “And we knew chemotherapy had not been real productive… Maybe this new treatment will change things. We don’t know, but we hope it does.”

Novocure’s Palti has devoted a lifetime of research to see that Gibbons and the other patients enrolled in the trials will see positive results. He explained to ISRAEL21c that he’s been studying electrical fields for over 40 years.

“In the early 1960s, I combined my MD and PhD on the subject of the distribution of electrical fields in living tissues. At that time, my research had nothing to do with cancer – it was about understanding how you stimulate nerves and muscles,” he said.

Palti continued his research, first at Hebrew University and then at the Technion, where he founded the Rappaport Institute of Research.

“At some point, I decided that I had had enough of basic science, and wanted to do something that would do some good in the world. I looked for something that would have value in the medical field and focused on cardio-vascular and cancer – which of course are the two major killers,” he said.

“It took me a while to get the idea to use electrical fields to affect dividing cells. Around 10 years ago, I started with models and experimenting in my basement office. I was far closer to the electrical field side than to oncology. It developed slowly, I got a small group together, still in my basement, and eventually got to the point that we were able to move outside and start a company to develop the idea.”

Today, the company employs about 40 people spread between their headquarters in Haifa and technical centers in the US and Europe. Palti, who retired from the Technion last year to devote all his time to Novocure, said that the company has deliberately stayed under the radar while developing the NovoTTF device.

“We’ve kept a very low profile, until this explosion with the publication of the trial results. We’ve been avoiding the press, because you don’t want to go around saying you can cure cancer before you’re pretty sure you have something.”

And according to the preliminary results, Palti and Novocure do seem to have something.


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