Lorenz M, Müller H H, Schramm H, Gassel H J, Rau H G, Ridwelski K, Hauss J, Stieger R, Jauch K W, Bechstein W O, Encke A
Ann Surg. 1998 Dec;228(6):756-62. doi: 10.1097/00000658-199812000-00006.
To determine the impact of adjuvant hepatic arterial infusion (HAI) on survival relative to resection alone in patients with radical resection of colorectal liver metastases.
Nearly 40% to 50% of all patients with colorectal carcinoma develop liver metastases. Curative resection results in a 5-year survival rate of 25% to 30%. Intrahepatic recurrence occurs after a median of 9 to 12 months in up to 60% of patients. The authors hypothesized that adjuvant intraarterial infusion of 5-fluorouracil (5-FU) might decrease the rate of intrahepatic recurrence and improve survival in patients with radical resection of colorectal liver metastases.
Between April 5, 1991, and December 31, 1996, patients with colorectal liver metastases from 26 hospitals were stratified by the number of metastases and the site of the primary tumor and randomized to resection of the liver metastases followed by adjuvant HAI of 5-FU (1000 mg/m2 per day for 5 days as a continuous 24-hour infusion) plus folinic acid (200 mg/m2 per day for 5 days as a short infusion), or liver resection only.
The first planned intention-to-treat interim analysis after inclusion of 226 patients and 91 events (deaths) showed a median survival of 34.5 months for patients with adjuvant therapy versus 40.8 months for control patients. The median time to progression was 14.2 months for the chemotherapy group versus 13.7 months for the control group. Grade 3 and 4 toxicities (World Health Organization), mainly stomatitis (57.6%) and nausea (55.4%), occurred in 25.6% of cycles and 62.9% of patients.
According to this planned interim analysis, adjuvant HAI, when used in this dose and schedule in patients with resection of colorectal liver metastases, reduced the risk of death at best by 15%, but at worst the risk of death was doubled. Thus, the chance of detecting an expected 50% improvement in survival by the use of HAI was only 5%. Patient accrual was therefore terminated.
确定辅助性肝动脉灌注（HAI）相对于单纯手术切除对结直肠癌肝转移根治性切除患者生存率的影响。
所有结直肠癌患者中近40%至50%会发生肝转移。根治性切除后的5年生存率为25%至30%。高达60%的患者在中位时间9至12个月后会出现肝内复发。作者推测辅助性肝动脉内灌注5-氟尿嘧啶（5-FU）可能会降低结直肠癌肝转移根治性切除患者的肝内复发率并提高生存率。
在1991年4月5日至1996年12月31日期间，来自26家医院的结直肠癌肝转移患者按转移灶数量和原发肿瘤部位进行分层，并随机分为两组，一组在肝转移灶切除后接受辅助性HAI，即5-FU（每天1000mg/m²，持续24小时输注5天）加亚叶酸（每天200mg/m²，短时间输注5天），另一组仅行肝切除。
纳入226例患者和91例事件（死亡）后的首次计划意向性治疗中期分析显示，接受辅助治疗的患者中位生存期为34.5个月，而对照组患者为40.8个月。化疗组的中位进展时间为14.2个月，对照组为13.7个月。3级和4级毒性反应（世界卫生组织标准）主要为口腔炎（57.6%）和恶心（55.4%），发生在25.6%的周期和62.9%的患者中。
根据本次计划的中期分析，辅助性HAI用于结直肠癌肝转移切除患者时，以该剂量和方案使用，充其量只能将死亡风险降低15%，但最坏的情况是死亡风险增加一倍。因此，通过使用HAI检测到预期生存率提高50%的可能性仅为5%。因此终止了患者入组。
