Domenge C, Orlowski S, Luboinski B, De Baere T, Schwaab G, Belehradek J, Mir L M
Department of Head and Neck Oncology, Institut Gustave-Roussy, Villejuif, France.
Cancer. 1996 Mar 1;77(5):956-63. doi: 10.1002/(sici)1097-0142(19960301)77:5<956::aid-cncr23>3.0.co;2-1.
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.
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.
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.
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.
电化学疗法（ECT）是一种新的抗肿瘤方法，它将全身应用博来霉素（BLM）与在肿瘤部位局部施加电脉冲（EP）相结合。这些电脉冲使组织中的细胞通透性增加，使博来霉素能够进入细胞内，并增强博来霉素的细胞毒性。作为我们最初对头颈部鳞状细胞癌（HNSCC）渗透结节患者进行的I期试验的扩展，我们测试了ECT方案的变体以确定如何改进它。
7例患有HNSCC或唾液腺或乳腺腺癌的多个和/或大渗透结节的患者接受了10次治疗。他们接受博来霉素治疗，随后在结节的相邻位置进行4次或8次短（100微秒）且强（1000或1300 V/cm-1）的电脉冲，以覆盖整个肿瘤表面。
我们确定在静脉注射博来霉素后8至28分钟之间为电脉冲给药的治疗窗口。我们显示患者对大量电脉冲具有耐受性，并且在动脉内注射博来霉素后或对腺癌结节进行ECT治疗具有可行性。获得了明显的抗肿瘤效果，尤其是在小结节中。在最大的结节中，我们观察到肿瘤坏死范围扩大。
对于大而厚的结节可以进行相对有效的ECT治疗，并且即使施加大量电脉冲，ECT仍然是安全的。然而，在本研究中，ECT对大结节的有效性低于先前治疗的小结节，这可能是由于外部电极不足所致。所报告的数据促使我们设计一种新的电脉冲给药装置。
