Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors.
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.
Kirson
Eilon D
ED
NovoCure Limited, Matam Advanced Technology Centre, Haifa 31905, Israel.
Dbalý
Vladimír
V
Tovarys
Frantisek
F
Vymazal
Josef
J
Soustiel
Jean F
JF
Itzhaki
Aviran
A
Mordechovich
Daniel
D
Steinberg-Shapira
Shirley
S
Gurvich
Zoya
Z
Schneiderman
Rosa
R
Wasserman
Yoram
Y
Salzberg
Marc
M
Ryffel
Bernhard
B
Goldsher
Dorit
D
Dekel
Erez
E
Palti
Yoram
Y
D000328:Adult; D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004599:Electric Stimulation Therapy / Q000009:adverse effects; D005260:Female; D005909:Glioblastoma / Q000473:pathology / Q000628:therapy*; D006801:Humans; D051379:Mice; D008839:Microelectrodes; D008954:Models, Biological; D009364:Neoplasm Recurrence, Local; D009374:Neoplasms, Experimental / Q000628:therapy; D010865:Pilot Projects; D051381:Rats; D011916:Rats, Inbred F344; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays