ANTITUMOR ELECTROCHEMOTHERAPY - NEW ADVANCES IN THE CLINICAL PROTOCOL

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 tis sue, allow BLM delivery inside the cells, and increase BLM cytotoxicit y. 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. S even patients with multiple and/or large permeation nodules of HNSCC o r of salivary or breast adenocarcinoma were treated in 10 sessions. Th ey received BLM followed by runs of four or eight short (100 mu s) 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 determin ed the therapeutic window for EP delivery to be between 8 and 28 minut es after BLM intravenous injection. We showed patient tolerance to a h igh number of EP, along with ECT feasibility after BLM intraarterial i njection or on adenocarcinoma nodules. Clear antitumor effects were ob tained, especially in the small nodules. In the largest nodules we obs erved extended tumor necrosis. CONCLUSIONS. Relatively efficient ECT c an be performed for large and thick 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 trea ted small nodules, probably due to external electrodes inadequacy. The data reported stimulated us to design a new device for EP delivery. ( C) 1996 American Cancer Society.