title: Antitumor electrochemotherapy: new advances in the clinical protocol.
abstract: BACKGROUND
  Electrochemotherapy (ECT) is a new antitumor approach that combines systemic bleomycin (BLM) with electric pulses (EP) delivered locally at the tumor site. These EP permeabilize the cells in the tissue, allow BLM delivery inside the cells, and increase BLM cytotoxicity. As an extension of our initial Phase I trial on patients with head and neck squamous cell carcinoma (HNSCC) permeation nodules, we tested variations of ECT protocol to determine how to improve it.
  
  
  METHODS
  Seven patients with multiple and/or large permeation nodules of HNSCC or of salivary or breast adenocarcinoma were treated in 10 sessions. They received BLM followed by runs of four or eight short (100 microseconds) and intense (1000 or 1300 V/cm-1) EP delivered at adjacent positions on the nodules to cover all of the tumor surface.
  
  
  RESULTS
  We determined the therapeutic window for EP delivery to be between 8 and 28 minutes after BLM intravenous injection. We showed patient tolerance to a high number of EP, along with ECT feasibility after BLM intraarterial injection or on adenocarcinoma nodules. Clear antitumor effects were obtained, especially in the small nodules. In the largest nodules we observed extended tumor necrosis.
  
  
  CONCLUSIONS
  Relatively efficient ECT can be performed for large and think nodules, and ECT remains safe even when a large number of EP are delivered. However, in this study, ECT's effectiveness on large nodules was lower than on the previously treated small nodules, probably due to external electrodes inadequacy. The data reported stimulated us to design a new device for EP delivery.
authors.affiliation: Department of Head and Neck Oncology, Institut Gustave-Roussy, Villejuif, France.
authors.forename: C
authors.initials: C
authors.lastname: Domenge
authors.forename: S
authors.initials: S
authors.lastname: Orlowski
authors.forename: B
authors.initials: B
authors.lastname: Luboinski
authors.forename: T
authors.initials: T
authors.lastname: De Baere
authors.forename: G
authors.initials: G
authors.lastname: Schwaab
authors.forename: J
authors.initials: J
authors.lastname: Belehradek
authors.forename: L M
authors.initials: LM
authors.lastname: Mir
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001761:Bleomycin / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D002463:Cell Membrane Permeability / Q000502:physiology; D003131:Combined Modality Therapy; D004566:Electrodes; D004594:Electrophysiology; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D004561:Transcutaneous Electric Nerve Stimulation / Q000009:adverse effects
chemical_list: D000903:Antibiotics, Antineoplastic; D001761:Bleomycin