It has recently been shown that low intensity, intermediate frequency, alternating electric fields (TTFields) lead to arrest of mitosis and rapid destruction of cancer cells. The effects are the result of field focusing by the hourglass cell geometry during cytokinesis and very high microtubule dipole moment (Kirson et al., 2004). TTFields at frequencies between 100 - 300 kHz and intensities in the range of 1-2 V/cm were applied to cell lines and to animal and human tumors by means of insulated surface electrodes. A portable, battery operated device was used to apply these fields to ambulatory patients with advanced solid tumors. Extensive studies showed that TTFields effectively inhibit the growth of 15 different cell lines in culture. When applied to animals for 5-7 days, TTFields inhibited the growth of syngeneic intradermal and metastatic melanoma in mice and intracerebral glioma in rats. Anaplastic kidney tumor growth was inhibited and extension of survival was seen in rabbits treated continuously for 1 month. Extensive safety studies showed no treatment related toxicities. Six patients have been treated to date in a phase I safety study in patients with locally advanced or metastatic solid tumors. Treatment was applied to breast carcinoma skin metastases (three patients), melanoma skin metastases (1 patient), the abdominal spread from pleural mesothelioma (1 patient) and to a rapidly progressive Glioblastoma Multiforme (1 patient). No treatment related serious adverse events were seen in any of the patients. The only treatment related adverse event was a local contact dermatitis, beneath the electrode’s contact gel, which appeared after the first 4 weeks of treatment in 2 of the patients. Responses consisted of 1 partial response (breast carcinoma skin metastasis), 4 stable disease for the duration of treatment and 1 non responder. A pilot phase II study of the efficacy and safety of TTFields in recurrent GBM patients is ongoing. So far, 10 recurrent GBM patients were treated without any treatment related serious adverse events. TTFields were continuously applied to outpatients until disease progression. One complete response, 1 partial response, 2 minimal responses and 5 stable diseases were documented by MRI. The median PFS in TTFields treated patients is 24 weeks at this time (2.5 times longer than expected for these patients), while 5 patients are still progression free. Four patients were progression free at six months from treatment initiation (PFS6=40%). Median OS is 42 weeks at present with 7 patients still alive. In summary, the extensive preclinical studies together with the preliminary clinical evidence suggest that TTFields could potentially be a safe and effective treatment modality for recurrent GBM and possibly other patients suffering from cancer.
[Proc Amer Assoc Cancer Res, Volume 47, 2006]