Low-intensity electric fields disrupt division of cancer cells in vitro and show promise against glioblastoma multiforme based on a pilot clinical trial, according to an article in the August issue of Physics Today. The pilot trial had 10 patients
The research was performed by an international team led by Yoram Palti of the Technion-Israel Institute of Technology in Haifa, Israel.

The alternating electric fields used in the study force ions in cells to oscillate hundreds of thousands of times per second. The electric fields have an intensity of only one or two volts per centimeter. Such low-intensity alternating electric fields were once believed to do nothing significant other than heat cells. However, researchers have shown that the fields disrupt cell division in tumor cells in vitro.

After intensively studying this effect in vitro and in laboratory animals, the researchers started a small human clinical trial to test its cancer-fighting ability. The technique was applied to 10 patients with recurrent glioblastoma multiforme. All patients had original tumors treated by other methods, but the cancer had started to recur in all cases.

Fitting the patients with electrodes that applied 200 kHz electric fields to the scalp at regular intervals for up to 18 hours per day, the researchers observed that the brain tumors progressed to advanced stages much slower than usual (median, 26 weeks) and sometimes even regressed.

The patients also lived considerably longer, with a median survival time of 62 weeks. While no control group existed, the results compared favorably to historical data for recurrent glioblastoma, in which the time for tumor progression is approximately 10 weeks and typical survival time is 30 weeks.

In addition, 3 of the 10 patients were still alive two years after the electrode therapy started. These results were announced in a recent issue of The Proceedings of the National Academy of Sciences (Kirson et al., PNAS 104, 10152-10157, June 12, 2007).

The Physics Today article explains these results in terms of the physical mechanisms that enable the electric fields to affect dividing cancer cells. In vitro, the electric fields were seen to have two effects on the tumor cells.

First, they slowed cell division. Cells that ordinarily took less than an hour to divide were still not completely divided after three hours of exposure to an electrical field of 200 kHz. Another group consisting of Luca Cucullo, Damir Janigro and their colleagues at the Cleveland Clinic, slowed cell division by applying electric fields with a much lower frequency, just 50 Hz. In addition, this protocol demonstrated the ability to decrease intrinsic drug resistance of the cells.

In the work with 200-kHz fields, the fields hampered formation and function of the mitotic spindle. Component microtubules contain elements with a high electric dipole moment, in which there is a large separation of opposite electric charges. Therefore, parts of the mitotic spindle are greatly influenced, and apparently disrupted, by an electric field.

The second effect of the 200 kHz fields is that they sometimes disintegrated the daughter cells just before they split from their partners.

The alternating electric fields are believed to have similar effects in the human glioblastomas. In contrast, the electric-field treatment poses little danger to normal brain tissue, because healthy brain cells do not divide. The electric fields were only observed to have disruptive effects on dividing cells. Based on the success of their initial human study, the researchers are working on another human clinical trial, this time with a control group receiving chemotherapy. The researchers are also investigating the possibility of combining the electric-field therapy with low-dose chemotherapy.