Vahrmeijer A L, Van Der Eb M M, Van Dierendonck J H, Kuppen P J, Van De Velde C J
Department of Surgery, Leiden University Medical Center, The Netherlands.
Semin Surg Oncol. 1998 Apr-May;14(3):262-8. doi: 10.1002/(sici)1098-2388(199804/05)14:3<262::aid-ssu11>3.0.co;2-w.
The prognosis of patients with irresectable liver metastases derived from colorectal cancer is invariably poor; unfortunately, these tumours show only minor responses to conventional anticancer agents. The best responses have been obtained by fluoropyrimidines delivered as continuous infusion into the hepatic artery (HAI): their rapid uptake and detoxification by liver cells results in relatively low systemic drugs levels. This approach increases mean survival duration from 17 to 26 months and, in few patients, causes "down-staging" that may result in resectability. To improve opportunities for chemotherapy, the technique of 1-hour recirculating perfusion of the vascularly isolated liver (isolated hepatic perfusion, IHP) was developed. If leakage to the systemic circulation is negligible-and the compounds used do not readily cause hepatotoxicity-IHP allows usage of drug doses that would be fatal if delivered systemically. Because alkylating agents generally have steep dose-response curves, mitomycin C (MMC) and melphalan (L-PAM) entered phase I/II studies on IHP. Using these drugs, IHP was performed in principle as a single procedure in 60 otherwise untreated patients at our institution. However, despite preliminary data that indicate impressive clinical responses are obtained, improvement over HAI will probably be minor. Because IHP is a complicated way of drug delivery, one could argue that its use is justified only when it has the potential to kill all tumour cells in the liver. We critically discuss the possibilities of IHP and/or the use of gene therapy in an IHP setting.
源自结直肠癌的不可切除肝转移患者的预后总是很差；不幸的是，这些肿瘤对传统抗癌药物仅表现出轻微反应。通过持续经肝动脉输注（HAI）氟嘧啶可获得最佳反应：它们被肝细胞快速摄取和解毒，导致全身药物水平相对较低。这种方法将平均生存时间从17个月延长至26个月，并且在少数患者中会导致“降期”，这可能会使肿瘤变得可切除。为了增加化疗机会，开发了血管隔离肝脏1小时循环灌注技术（隔离肝灌注，IHP）。如果向体循环的渗漏可忽略不计，并且所使用的化合物不易引起肝毒性，那么IHP允许使用如果全身给药将是致命的药物剂量。由于烷化剂通常具有陡峭的剂量反应曲线，丝裂霉素C（MMC）和美法仑（L-PAM）进入了关于IHP的I/II期研究。在我们机构，使用这些药物，IHP原则上作为单一程序在60例未接受过其他治疗的患者中进行。然而，尽管初步数据表明获得了令人印象深刻的临床反应，但与HAI相比，改善可能很小。由于IHP是一种复杂的给药方式，有人可能会认为只有当它有可能杀死肝脏中的所有肿瘤细胞时，其使用才是合理的。我们批判性地讨论了IHP和/或在IHP环境中使用基因治疗的可能性。
