電脈衝化療是一種通過施加局部電脈衝,增加細胞通透性,將通常情況下無法進入細胞內部的藥物送入細胞內,從而達到殺死癌細胞目的的治療癌症的療法[1][2]。配合博萊黴素順鉑使用電脈衝化療治療皮內和皮下腫瘤的研究已經進入臨床階段。[3][4][5][6][7][8][9][10][11][12]第一次伯萊黴素電脈衝化療於1991年在法國Gustave Roussy研究所實現[13],第一次順鉑電脈衝化療則於1995年在斯洛文尼亞盧布爾雅那腫瘤研究所實現[14]。其後,來自全球多個國家(愛爾蘭、澳洲、奧地利、比利時、保加利亞、丹麥、德國、法國、美國、墨西哥、尼加瓜拉、波蘭、葡萄牙、日本、瑞士、斯洛文尼亞、西班牙、希臘、匈牙利、意大利、英國)的4000多名患者接受了電脈衝化療。最近,為了治療體內腫瘤,開發了通過外科手術內窺鏡皮下穿刺等方法到達患處的新的電脈衝化療方法。[15][16]

物理原理

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當細胞暴露在足夠強的電場中時,跨膜電位細胞膜內外的電勢差)將會增加,這會引發細胞膜結構重排[17][18][19][20][21][22],從而導致細胞膜通透性增加,進而允許通常無法穿過細胞膜的分子進入細胞[13][23][24]。這一被稱為電穿孔英語electroporation電通透英語electropermeabilization的現象,正被廣泛應用到抗腫瘤治療中。這種治療方案就是廣為熟知的電脈衝化療。電脈衝化療只採用短暫但強勁的單級直流電,儘管在體外培養的細胞和細菌中可以用電場強度隨時間衰減的脈衝。在生物體內完整組織中,脈衝的電場強度依不同組織和電極的形狀和位置而不同。在一般的腫瘤治療中,電脈衝強度需要在腫瘤範圍內達到400V/cm。通常每次連續施加8個持續100微秒[25]的脈衝。在最初的試驗中,施加脈衝的頻率為1Hz,而現在通常採用5000Hz,因為這可以大大降低患者的不適感和治療的持續時間[26][27]。而在治療靠近心臟的腫瘤時,脈衝應和心肌的絕對不應期同步,從而儘可能降低電脈衝影響心臟正常功能的可能性。[28]

治療說明

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電脈衝治療首先需要對全身或局部引入不通透或低通透的細胞毒素藥物。然後,當腫瘤區域藥物濃度達到峰值時直接對該區域施加脈衝電場[12]。脈衝電場可以在細胞膜上產生納米級缺陷,從而方便藥物進入細胞。在施加電場期間以及電場消失後的一段時間內,藥物分子可以自由擴散進入細胞質,從而實現抗腫瘤效果。如果藥物濃度足夠,可以通過在不同的地方插入電極和施加多次電場來治療整個腫瘤。[25]如果首次治療時因腫瘤太大而無法對整個腫瘤施加電脈衝化療,也可以在幾周或幾個月後繼續治療。

療效和相關性

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一些二期臨床實驗證明,使用博萊黴素和順鉑的電脈衝化療對皮內或皮下肉瘤的客觀應答率超過80%。[4][29]電脈衝化療在縮小皮膚腫瘤和皮下腫瘤的大小上比化療更快更有效。電脈衝化療對黑色素瘤Kaposi肉瘤鱗狀細胞癌基底細胞癌腺癌乳腺癌均有療效。[4][5][6][7][9][10][30]初步表明也很有希望可以利用電脈衝療法治療內部腫瘤(例如肝轉移腫瘤)。

安全性

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電脈衝化療所使用的藥物濃度比普通化療所使用的更低,因此沒有常規化療所引起的不良反應。適當的麻醉可以減輕電脈衝引起的不適症狀,從而可以把疼痛感控制在病人可以接受的範圍內。除去電脈衝引起的疼痛以外,脈衝期間的肌肉收縮是患者唯一的不適。[4][31]脈衝同時會引起短暫的缺血。在治療區域內,正常組織內的血液循環會被打斷幾分鐘[32][33],但是由於時間短暫,所以並不會產生缺血反應;相反地,腫瘤組織內部的缺血時間會更長,從而對抑制腫瘤也有一定幫助。在一項以建立歐洲電脈衝化療標準手術程序為目的的醫療實驗中,大部分接受調查患者表示如果需要,願意再次接受電脈衝化療[4],因此可以推斷電脈衝化療並不特別令人痛苦或者緊張。[4][34]

獸醫應用

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電脈衝化療同樣可以應用於犬類的腫瘤治療。巴西、法國、意大利、愛爾蘭、斯洛文尼亞、英國及台灣的一些醫療中心可以提供針對各種腫瘤的治療。[34]

評論

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電脈衝化療在多個歐盟國家(波蘭、丹麥、德國、葡萄牙、斯洛文尼亞、希臘、意大利和英國)都已經獲得認可和醫療補貼。意大利Carpy Igea, s.r.l.生產的Cliniporator儀被認證為醫療器具並和歐洲電脈衝化療標準手術程序一起向市場推廣。[4]

參考資料

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參考

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