Larkin John O, Collins Christopher G, Aarons Simon, Tangney Mark, Whelan Maria, O'Reily Seamus, Breathnach Oscar, Soden Declan M, O'Sullivan Gerald C
Cork Cancer Research Centre, Leslie C. Quick Jr. Cancer Laboratory, Biosciences Institute & Mercy University Hospital, National University of Ireland, Cork, Ireland.
Ann Surg. 2007 Mar;245(3):469-79. doi: 10.1097/01.sla.0000250419.36053.33.
To develop an optimized, reproducible system of electrochemotherapy, and to investigate its clinical application in patients with cutaneous or subcutaneous recurrences of inoperable or progressive disease recalcitrant to current anticancer treatments.
Electrochemotherapy is the application of electric pulses to tumor tissue, rendering the cell membranes permeable to otherwise impermeant or poorly permeant anticancer drugs. This facilitates a potent local cytotoxic effect.
The optimal parameters for electrical pulses and bleomycin concentration were obtained in vitro and then applied to tumors derived from 4 histologically distinct human cancer cell lines (7860, PC3, OE19, MCF-7) established in athymic nude mice. Comparison was made with tumors that received bleomycin alone, electric pulses alone, and untreated controls. The optimized electrochemotherapy was then applied to patients with cutaneous or subcutaneous tumors, of any histologic type, recurrent or metastatic and unresponsive to standard chemotherapy and/or radiotherapy regimens. Tumors were assessed at monthly intervals to determine response to the treatment.
In vivo: Using the optimal parameters ascertained in vitro, all tumors treated by electrochemotherapy with bleomycin (n = 24) had significantly regressed (P < 0.001, all 4 lines) compared with control tumors (n = 72). Twelve tumors completely regressed (50%) following a single application, with 12 partial regressions (50%). Clinical: In 30 patients (111 tumors), none of the treated tumors progressed. Sixty percent of tumors (66 of 111) showed complete regression, 22% (24 of 111) partial response, and 18% (21 of 111) no change. Electrochemotherapy was more effective in smaller tumors (<3 cm), 71% (64 of 90) showing complete regression, 20% (18 of 90) partial response, and 9% (8 of 90) no change.
Electrochemotherapy parameters optimized in vitro are applicable in vivo. This treatment is effective in athymic nude mice for all histologic types indicating a nonimmunologic mode of action. In clinical application, electrochemotherapy is an effective, safe, and reproducible therapy. Patients with cutaneous or subcutaneous tumors previously refractory to surgical intervention, systemic chemotherapy, and/or radiotherapy responded successfully irrespective of histologic type.
开发一种优化的、可重复的电化学疗法系统，并研究其在无法手术或病情进展且对当前抗癌治疗耐药的皮肤或皮下复发患者中的临床应用。
电化学疗法是将电脉冲施加于肿瘤组织，使细胞膜对原本无法通透或通透性差的抗癌药物具有通透性。这有助于产生强大的局部细胞毒性作用。
在体外获得电脉冲和博来霉素浓度的最佳参数，然后将其应用于在无胸腺裸鼠中建立的4种组织学上不同的人类癌细胞系（7860、PC3、OE19、MCF-7）衍生的肿瘤。与单独接受博来霉素、单独接受电脉冲和未治疗的对照组肿瘤进行比较。然后将优化的电化学疗法应用于患有任何组织学类型的皮肤或皮下肿瘤、复发或转移且对标准化疗和/或放疗方案无反应的患者。每月对肿瘤进行评估以确定对治疗的反应。
体内：使用体外确定的最佳参数，与对照肿瘤（n = 72）相比，所有接受博来霉素电化学疗法治疗的肿瘤（n = 24）均有显著消退（P < 0.001，所有4种细胞系）。单次治疗后12个肿瘤完全消退（50%），12个部分消退（50%）。临床：在30例患者（111个肿瘤）中，所有治疗的肿瘤均未进展。60%的肿瘤（111个中的66个）显示完全消退，22%（111个中的24个）部分缓解，18%（111个中的21个）无变化。电化学疗法在较小的肿瘤（<3 cm）中更有效，71%（90个中的64个）显示完全消退，20%（90个中的18个）部分缓解，9%（90个中的8个）无变化。
体外优化的电化学疗法参数适用于体内。这种治疗方法在无胸腺裸鼠中对所有组织学类型均有效，表明其作用方式是非免疫性的。在临床应用中，电化学疗法是一种有效、安全且可重复的治疗方法。患有先前对手术干预、全身化疗和/或放疗难治的皮肤或皮下肿瘤的患者，无论组织学类型如何，均成功获得反应。
