Hyperthermie: Electromagnetische velden - TT fields therapie als aanvulling op andere behandelingen zorgen voor uitstekende resultaten bij o.a. borstkanker, hersentumoren en longtumoren, aldus verschillende studies.

26 mei 2009: Bron: Pubmed verschillende studieabstracten.

Dat electro-hyperthermie als aanvulling voor goede resultaten zorgt in een behandeling van kanker, bij zowel solide tumoren als bij bij niet solide tumoren is en wordt bevestigd in studies met de NOVOcure apparatuur. En zonder ook maar enige toxische bijwerking. Zij noemen het geen electro-hyperthermie maar Alternating Electric Fields - TT-fields = electro-magnetische velden. Maar het principe hoe het werkt is hetzelfde. Dat zij dit zo noemen heeft alles te maken met de strijd om de macht op de wereldmarkt om apparatuur te kunnen en mogen leveren. Er zijn wereldwijd drie grote leveranciers van deze apparatuur, NOVOcure, Celcius 42 en met wat andere techniek BSD die werken met antennes (laag frequente radiogolven) en waarbij het gevaar van verbranden groter is dan bij de electro hyperthermie apparatuur van NVOcure en Celcius 42. Hier een aantal studies op een rijtje waarbij de TT-field apparatuur is gebruikt bij borstkanker, longtumoren en hersentumoren. Met hoewel de studies klein waren uitzonderlijk goede resultaten. Maar leest u maar zelf.

ET-03. THE EFFICACY OF TEMOZOLOMIDE IN VITRO AND IN PATIENTS WITH NEWLY DIAGNOSED GBM IS ENHANCED BY ADJUVANT EXPOSURE TO ALTERNATING ELECTRIC FIELDS (TTFIELDS)

Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs.

Kirson ED, Giladi M, Gurvich Z, Itzhaki A, Mordechovich D, Schneiderman RS, Wasserman Y, Ryffel B, Goldsher D, Palti Y.

NovoCure Limited, Matam Advanced Technology Centre, Topaz Bldg., 31905, Haifa, Israel, Eilon@novo-cure.com.

Tumor treating fields (TTFields) are low intensity, intermediate frequency, alternating electric fields used to treat cancerous tumors. This novel treatment modality effectively inhibits the growth of solid tumors in vivo and has shown promise in pilot clinical trials in patients with advanced stage solid tumors. TTFields were tested for their potential to inhibit metastatic spread of solid tumors to the lungs in two animal models: (1) Mice injected with malignant melanoma cells (B16F10) into the tail vein, (2) New Zealand White rabbits implanted with VX-2 tumors within the kidney capsule. Mice and rabbits were treated using two-directional TTFields at 100-200 kHz. Animals were either monitored for survival, or sacrificed for pathological and histological analysis of the lungs. The total number of lung surface metastases and the absolute weight of the lungs were both significantly lower in TTFields treated mice then in sham control mice. TTFields treated rabbits survived longer than sham control animals. This extension in survival was found to be due to an inhibition of metastatic spread, seeding or growth in the lungs of TTFields treated rabbits compared to controls. Histologically, extensive peri- and intra-tumoral immune cell infiltration was seen in TTFields treated rabbits only. These results raise the possibility that in addition to their proven inhibitory effect on the growth of solid tumors, TTFields may also have clinical benefit in the prevention of metastatic spread from primary tumors.

PMID: 19387848 [PubMed - as supplied by publisher]

Comment in:: Onkologie. 2008 Jul;31(7):357-8.

A pilot study with very low-intensity, intermediate-frequency electric fields in patients with locally advanced and/or metastatic solid tumors.

Salzberg M, Kirson E, Palti Y, Rochlitz C.

University Hospital Basel, Switzerland. msalzberg@pharmabrains.ch

BACKGROUND: The transmission of electric fields using insulated electrodes has demonstrated that very low-intensity, properly tuned, intermediate-frequency electric fields, termed tumor-treating fields (TTFields), selectively stunts tumor cell growth and is accompanied by a decrease in tumor angiogenesis.

PATIENTS AND METHODS: This open, prospective pilot study was designed to evaluate the safety, tolerability, and efficacy profile of TTFields treatment in patients with locally advanced and/or metastatic solid tumors using the NovoTTF100A(TM) device. All 6 patients were heavily pre-treated with several lines of therapy; no additional standard treatment option was available to them. TTFields treatment using continuous NovoTTF-100A lasted a minimum of 14 days and was very well tolerated.

RESULTS: No related serious adverse events occurred. Outcomes showed 1 partial response of a treated skin metastasis from a primary breast cancer, 3 cases where tumor growth was arrested during treatment, and 1 case of disease progression. One mesothelioma patient experienced lesion regression near TTFields with simultaneous tumor stability or progression in distal areas.

CONCLUSION: Although the number of patients in this study is small, the lack of therapy toxicity and the efficacy observed in data gathered to date indicate the potential of TTFields as a new treatment modality for solid tumors, definitely warranting further investigation. (c) 2008 S. Karger AG, Basel

PMID: 18596382 [PubMed - indexed for MEDLINE]

1: Onkologie. 2008 Jul;31(7):362-5. Epub 2008 Jun 24.

Links

Posted on: 08/29/2008

From:

Abstracts for the Thirteenth Annual Meeting of the Society for Neuro-Oncology

November 20–23, 2008

ET-03. THE EFFICACY OF TEMOZOLOMIDE IN VITRO AND IN PATIENTS WITH NEWLY DIAGNOSED GBM IS ENHANCED BY ADJUVANT EXPOSURE TO ALTERNATING ELECTRIC FIELDS (TTFIELDS)
Eilon Kirson1, Vladimir Dbaly2, Frantisek Tovarys2, Josef Vymazal3, Rosa Schneiderman4, Yoram Wasserman5, and Yoram Palti1; 1NovoCure Ltd., Haifa, Israel; 2Neurosurgery, Na Homolce Hospital, Prague, Czech Republic; 3Radiology, Na Homolce Hospital, Prague, Czech Republic; 4Biology, NovoCure Ltd., Haifa, Israel; 5Engineering, NovoCure Ltd., Haifa, Israel.

BACKGROUND: Alternating electric fields (TTFields) have been shown to exert anti-tumor activity, destroying cycling cells during mitosis. Preliminary clinical experience suggests efficacy against recurrent glioma; this technique is currently undergoing phase III evaluation in patients with recurrent glioblastoma. In vitro synergy with various chemotherapeutic agents has been shown in breast and lung cancer cell lines (Kirson et al, AACR 2007).

METHODS: In the present study, the effects of TTFields alone and in combination with DTIC were tested in human glioma (GBM) cells in vitro (U-87). Subsequently, the effects of TTFields in combination with maintenance temozolomide (TMZ) were tested in an open-label, single-arm, prospective, pilot clinical trial. Ten patients (median age 54 years, KPS > 70, gross total tumor resection in 4 patients [40%]) with newly diagnosed GBM were treated with standard TMZ/RT. During the maintenance TMZ administration, TTFields were applied continually (18 hours a day, on average) for up to 18 months . All patients were followed on a monthly basis (including monthly contrast magnetic resonance imaging
of the brain). The primary endpoints were feasibility and toxicity, time to disease progression, and overall survival. Results were compared to concurrent and historical controls.

RESULTS: In vitro, full additivity of the inhibitory effects of DTIC and TTFields was observed when both treatments were applied concomitantly to GBM cells in culture. This finding was true for all DTIC concentrations tested. In the pilot clinical trial, no device–related, systemic, adverse events were noted throughout the treatment with TTFields (cumulative treatment time more than 170 months; median administration time 12 months). Over time, a mild to moderate skin irritation appeared beneath the electrode gel in all patients. Median time to disease progression was 155 weeks in patients treated with combined TMZ and TTFields, compared to 31 weeks in concurrent control patients treated with TMZ alone (hazard ratio 3.7; 95% confidence interval 2.1–6.7). Half the patients were still progression-free at the end of the trial. Median overall survival was . 40 months in patients treated with combined TMZ and TTFields, compared to 14.7 months reported for historical controls (Stupp et al, 2004). Eight of the 10 patients were still alive at the end of this study.

CONCLUSIONS: These promising findings suggest that TTFields can be applied over many months without significant toxicity. The combination with standard TMZ chemotherapy may greatly enhance the anti-tumor effect of TMZ translating into prolonged time to progression and survival.

1: BMC Med Phys. 2009 Jan 8;9:1. Links

Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields (TTFields).

Kirson ED, Schneiderman RS, Dbalý V, Tovarys F, Vymazal J, Itzhaki A, Mordechovich D, Gurvich Z, Shmueli E, Goldsher D, Wasserman Y, Palti Y.

NovoCure Ltd,, MATAM Advanced Technology Centre, Haifa 31905, Israel. eilon@novo-cure.com.

ABSTRACT: BACKGROUND: The present study explores the efficacy and toxicity of combining a new, non-toxic, cancer treatment modality, termed Tumor Treating Fields (TTFields), with chemotherapeutic treatment in-vitro, in-vivo and in a pilot clinical trial.

METHODS: Cell proliferation in culture was studied in human breast carcinoma (MDA-MB-231) and human glioma (U-118) cell lines, exposed to TTFields, paclitaxel, doxorubicin, cyclophosphamide and dacarbazine (DTIC) separately and in combinations. In addition, we studied the effects of combining chemotherapy with TTFields in an animal tumor model and in a pilot clinical trial in recurrent and newly diagnosed GBM patients.

RESULTS: The efficacy of TTFields-chemotherapy combination in-vitro was found to be additive with a tendency towards synergism for all drugs and cell lines tested (combination index </= 1). The sensitivity to chemotherapeutic treatment was increased by 1-3 orders of magnitude by adjuvant TTFields therapy (dose reduction indexes 23 - 1316). Similar findings were seen in an animal tumor model. Finally, 20 GBM patients were treated with TTFields for a median duration of 1 year. No TTFields related systemic toxicity was observed in any of these patients, nor was an increase in Temozolomide toxicity seen in patients receiving combined treatment. In newly diagnosed GBM patients, combining TTFields with Temozolomide treatment led to a progression free survival of 155 weeks and overall survival of 39+ months.

CONCLUSION: These results indicate that combining chemotherapeutic cancer treatment with TTFields may increase chemotherapeutic efficacy and sensitivity without increasing treatment related toxicity.

PMID: 19133110 [PubMed - in process]

Zo introduceerden we vorig jaar een oproep voor deelname aan een studie met een NOVOcure apparatuur thuis.

TTF-100A (Tumor Treating Fields) - een apparaatje dat de directe omgeving en de tumoren zelf "bewerkt" met electrische velden en gewoon thuis kan worden gebruikt zorgt voor zeer opmerkelijke resultaten in een trial bij 4 borstkankerpatienten met lokaal uitgezaaide borstkanker in combinatie met chemo. Bij alle vier verdwenen de tumoren 85% tot 100%. 1 patiente bereikte een totale remissie, dus werd klinisch kankervrij. Er zijn een aantal dierstudies aan deze piltostudie voorafgegaan. Zie o.a. deze http://cancerres.aacrjournals.org/cgi/content/full/64/9/3288 waar heel gedetailleerd staat beschreven hoe deze methodiek werkt. Interessant om te zien dat de apparaten waarmee hyperthermie in Duitsland wordt gegeven een soortgeljk mechanisme gebruiken. Ook deze apparaten creeeren , maar dan met magnetische velden en zal eens navragen in hoeverre dit hetzelfde is, in de tumorcel warmte waardoor de kankercellen doodgaan. Zie ook deze http://www.pnas.org/cgi/content/abstract/0702916104v1?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=kirson&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT waar wordt beschreven dat in een pilotstudie met patienten met een hersentumor de overal overlevingstijd wordt verdubbeld met alleen gebruik van de TTF - 100A.

eierstokkanker, hyperthermie