For years, electric fields were rumored to cause cancer. Now there's reason to believe they might fight it--and in some cases even destroy it. Researchers have used low-intensity, intermediate-frequency electric fields to combat an aggressive brain cancer known as glioblastoma multiforme (GBM). The strategy pinpoints tumors without invasive brain surgery and has more than doubled survival time in preliminary studies.
The new approach exploits a cog in the cell-division pathway. When cells divide, a molecular motor called the microtubule spindle helps segregate chromosomes into the resulting daughter cells. Resembling a set of strings, the spindle is made of electrically polar macromolecules that are sensitive to electric fields. Previous work has shown that if a 200-kHz field is applied to these macromolecules, the spindle can't form properly. As a result, cells stop dividing and eventually die.
Because cancer results from uncontrolled cell division, a team of researchers from NovoCure Limited, a biotech company located in Haifa, Israel, and other institutes in Israel and Europe began a clinical trial with 10 GBM patients who had not been helped by standard therapies. They gave each patient a lightweight, battery-operated device, called the NovoTTF-100A, which generates 200-kHz fields. (Power lines, for comparison, generate fields of about 60 Hz.) Then the doctors glued four sets of insulated electrodes on the scalp so as to focus the field on the tumor. Patients wore the device on their heads 24 hours a day for 18 months or until the disease worsened.
In eight cases, the electric fields increased life expectancy. Although there was no control group, the researchers compared the volunteers' results to historical studies of GBM trials. The median overall survival time for all patients was 62 weeks compared to the 29-week average of more than 800 patients at a similar stage of the disease who had been treated with chemotherapy. The tumors stopped growing in four patients and shrank in another four. In one case, a patient's tumor completely disappeared and the patient has remained tumor-free for 2.5 years after the trial; going into the study she had an expected survival time of about 6 months, says physician Eilon Kirson of NovoCure. Tumors continued to grow in two other patients.
The device is ideal for those with GBM because it only acts on the brain and lacks chemotherapy's systemic side effects, says Eric Wong, a neuro-oncologist at Beth Israel Deaconess Medical Center in Boston, Massachusetts. Because tumor cells in the brain frequently divide, normal brain cells would remain unaffected by the electric fields, the team reports online this week in the Proceedings of the National Academy of Sciences. However, electric field brain stimulation has produced seizures in laboratory rats, a phenomenon known as kindling, Wong notes, so "I would be concerned most with whether there would be seizures [in humans]." Still, he says, no increased rates of seizures were seen in the 10 patients.
Wong was not involved in the study, but he is part of a team of researchers currently testing the device in a phase III clinical trial, which includes more than 200 glioblastoma patients in the United States and Europe. If it works, the researchers hope to apply electric field therapy to additional types of cancer, such as breast cancer and non-small-cell lung cancer.