title: Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields (TTFields).
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 <or= 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.
  
  
  CONCLUSIONS
  These results indicate that combining chemotherapeutic cancer treatment with TTFields may increase chemotherapeutic efficacy and sensitivity without increasing treatment related toxicity.
authors.affiliation: NovoCure Ltd,, MATAM Advanced Technology Centre, Haifa 31905, Israel. eilon@novo-cure.com
authors.forename: Eilon D
authors.initials: ED
authors.lastname: Kirson
authors.forename: Rosa S
authors.initials: RS
authors.lastname: Schneiderman
authors.forename: Vladimír
authors.initials: V
authors.lastname: Dbalý
authors.forename: Frantisek
authors.initials: F
authors.lastname: Tovarys
authors.forename: Josef
authors.initials: J
authors.lastname: Vymazal
authors.forename: Aviran
authors.initials: A
authors.lastname: Itzhaki
authors.forename: Daniel
authors.initials: D
authors.lastname: Mordechovich
authors.forename: Zoya
authors.initials: Z
authors.lastname: Gurvich
authors.forename: Esther
authors.initials: E
authors.lastname: Shmueli
authors.forename: Dorit
authors.initials: D
authors.lastname: Goldsher
authors.forename: Yoram
authors.initials: Y
authors.lastname: Wasserman
authors.forename: Yoram
authors.initials: Y
authors.lastname: Palti