Kirson Eilon D, Dbalý Vladimír, Tovarys Frantisek, Vymazal Josef, Soustiel Jean F, Itzhaki Aviran, Mordechovich Daniel, Steinberg-Shapira Shirley, Gurvich Zoya, Schneiderman Rosa, Wasserman Yoram, Salzberg Marc, Ryffel Bernhard, Goldsher Dorit, Dekel Erez, Palti Yoram
NovoCure Limited, Matam Advanced Technology Centre, Haifa 31905, Israel.
Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10152-7. doi: 10.1073/pnas.0702916104. Epub 2007 Jun 5.
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.
我们最近发现,低强度、中频电场通过抗微管作用机制抑制体外癌细胞生长。使用植入电极时,这些电场也被证明可抑制小鼠皮肤肿瘤的生长。本研究将这些发现扩展至其他细胞系[人乳腺癌;MDA-MB-231,以及人非小细胞肺癌(H1299)],并使用外部绝缘电极应用于动物肿瘤模型(皮内B16F1黑色素瘤和颅内F-98胶质瘤)。这些发现促使开展了一项关于TTFields对10例复发性胶质母细胞瘤(GBM)患者疗效的试点临床试验。这些患者的疾病进展中位时间为26.1周,总生存中位时间为62.2周。这些疾病进展时间和总生存值比报告的历史对照患者中位数高出一倍多。在所有患者累计治疗超过70个月后,未观察到与设备相关的严重不良事件。唯一观察到的与设备相关的副作用是电场传输电极下方出现轻度至中度接触性皮炎。我们得出结论,TTFields是一种安全有效的新治疗方式,能有效减缓体外、体内肿瘤生长,如此处所示,对人类癌症患者也有效。
Proc Natl Acad Sci U S A. 2007-6-12
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