TY - JOUR
T1 - Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors
AU - Kirson, Eilon D.
AU - Dbalý, Vladimír
AU - Tovaryš, František
AU - Vymazal, Josef
AU - Soustiel, Jean F.
AU - Itzhaki, Aviran
AU - Mordechovich, Daniel
AU - Steinberg-Shapira, Shirley
AU - Gurvich, Zoya
AU - Schneiderman, Rosa
AU - Wasserman, Yoram
AU - Salzberg, Marc
AU - Ryffel, Bernhard
AU - Goldsher, Dorit
AU - Dekel, Erez
AU - Palti, Yoram
PY - 2007/6/12
Y1 - 2007/6/12
N2 - We have recently shown that low intensity, intermediate frequency, electric fields inhibit by an anti-microtubule mechanism of action, cancerous cell growth in vitro. Using implanted electrodes, these fields were also shown to inhibit the growth of dermal tumors in mice. The present study extends these findings to additional cell lines [human breast carcinoma; MDA-MB-231, and human non-small-cell lung carcinoma (H1299)] and to animal tumor models (intradermal B16F1 melanoma and intracranial F-98 glioma) using external insulated electrodes. These findings led to the initiation of a pilot clinical trial of the effects of TTFields in 10 patients with recurrent glioblastoma (GBM). Median time to disease progression in these patients was 26.1 weeks and median overall survival was 62.2 weeks. These time to disease progression and OS values are more than double the reported medians of historical control patients. No device-related serious adverse events were seen after >70 months of cumulative treatment in all of the patients. The only device-related side effect seen was a mild to moderate contact dermatitis beneath the field delivering electrodes. We conclude that TTFields are a safe and effective new treatment modality which effectively slows down tumor growth in vitro, in vivo and, as demonstrated here, in human cancer patients.
AB - We have recently shown that low intensity, intermediate frequency, electric fields inhibit by an anti-microtubule mechanism of action, cancerous cell growth in vitro. Using implanted electrodes, these fields were also shown to inhibit the growth of dermal tumors in mice. The present study extends these findings to additional cell lines [human breast carcinoma; MDA-MB-231, and human non-small-cell lung carcinoma (H1299)] and to animal tumor models (intradermal B16F1 melanoma and intracranial F-98 glioma) using external insulated electrodes. These findings led to the initiation of a pilot clinical trial of the effects of TTFields in 10 patients with recurrent glioblastoma (GBM). Median time to disease progression in these patients was 26.1 weeks and median overall survival was 62.2 weeks. These time to disease progression and OS values are more than double the reported medians of historical control patients. No device-related serious adverse events were seen after >70 months of cumulative treatment in all of the patients. The only device-related side effect seen was a mild to moderate contact dermatitis beneath the field delivering electrodes. We conclude that TTFields are a safe and effective new treatment modality which effectively slows down tumor growth in vitro, in vivo and, as demonstrated here, in human cancer patients.
KW - Cancer
KW - Glioblastoma
KW - Tumor treating fields
UR - http://www.scopus.com/inward/record.url?scp=34547148613&partnerID=8YFLogxK
U2 - 10.1073/pnas.0702916104
DO - 10.1073/pnas.0702916104
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C2 - 17551011
AN - SCOPUS:34547148613
SN - 0027-8424
VL - 104
SP - 10152
EP - 10157
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 24
ER -