Lorenz Matthias, Staib-Sebler Elsbeth, Gog Christiane, Proschek D, Jauch K-W, Ridwelski K, Hohenberger W, Gassel H-J, Lehmann Ute, Vestweber K-H, Padberg W, Zamzow Karin, Müller H-H
Department of General and Vascular Surgery, Johann-Wolfgang-Goethe-University Frankfurt, Frankfurt au Main.
Zentralbl Chir. 2003 Feb;128(2):87-94. doi: 10.1055/s-2003-37760.
Since there are currently no data available from a prospective trial, the primary objective of this prospective study was to investigate whether the rate of R0-liver resections without morbidity would be at least 50 % in patients with neoadjuvant chemotherapy for colorectal liver metastases.
42 patients were treated with a biweekly FOLFOX regimen. Chemotherapy consisted of a 2-hour infusion of folinic acid (FOL) 500 mg/m2, followed by a 24-hour infusion of 5- fluorouracil (F) 2000 mg/m2 daily for two days. Oxaliplatin (OX) 85 mg/m 2 was given simultaneously with FOL. Treatment allocation was randomized with either 3 or 6 cycles for the final 30 patients. A liver resection was performed 2 to 5 weeks after the final infusion.
An objective response was observed in 20 of 42 patients (response rate was 27 % higher after 6 cycles). Liver resection (R0) could be performed in 34 patients. Postoperative complications were reported in 14 patients (13 occurring within 30 days after resection) and severe complications in 5 cases (including two deaths after extended resection). Liver failure and persistent biliary fistula were the most frequently documented complications. There was no relevant difference in safety criteria between 3 and 6 applications.
The use of neoadjuvant chemotherapy in resectable liver metastases induced significant remissions without increasing morbidity. The rate of severe complications and cases of no R0-resection in this study was 31 % and was with that significantly lower than 50 % (95 % CI 17.6 %-47.1 %). The risk to the patient is therefore acceptable when undergoing neoadjuvant treatment in a prospective intergroup trial.
由于目前尚无前瞻性试验的数据，本前瞻性研究的主要目的是调查接受新辅助化疗的结直肠癌肝转移患者中，无并发症的R0肝切除率是否至少为50%。
42例患者接受每两周一次的FOLFOX方案治疗。化疗包括静脉滴注亚叶酸（FOL）500mg/m²，持续2小时，随后连续两天每日静脉滴注5-氟尿嘧啶（F）2000mg/m²，持续24小时。奥沙利铂（OX）85mg/m²与FOL同时给药。对最后30例患者进行随机分组，分别接受3个周期或6个周期的治疗。在最后一次输注后2至5周进行肝切除术。
42例患者中有20例观察到客观缓解（6个周期后的缓解率高出27%）。34例患者可行肝切除术（R0）。14例患者报告有术后并发症（13例发生在切除术后30天内），5例出现严重并发症（包括扩大切除术后2例死亡）。肝衰竭和持续性胆瘘是最常见的并发症。3次和6次应用之间的安全性标准无显著差异。
在可切除的肝转移瘤中使用新辅助化疗可诱导显著缓解，且不增加并发症发生率。本研究中严重并发症发生率和非R0切除病例率为31%，显著低于50%（95%CI 17.6%-47.1%）。因此，在前瞻性组间试验中接受新辅助治疗时，患者的风险是可以接受的。
