Tsutsumi Soichi, Yamaguchi Satoru, Tsuboi Kaori, Fukasawa Takaharu, Tabe Yuichi, Asao Takayuki, Kuwano Hiroyuki
Department of General Surgical Science (Surgery I), Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
Hepatogastroenterology. 2008 Jul-Aug;55(85):1419-22.
BACKGROUND/AIMS: Hepatic arterial infusion (HAI) chemotherapy has a number of limitations, including a low rate of complete response and frequent extrahepatic recurrence, in colorectal cancer (CRC) patients with unresectable hepatic metastases. A clinical trial was planned to assess the safety and efficacy of combination chemotherapy of HAI and oral administration of UFT and leucovorin (UZEL) in CRC patients with unresectable liver metastases.
Sixteen CRC patients with unresectable liver metastases were treated with concurrent HAI and systemic oral UFT/UZEL. Eligible patients were previously untreated (except for adjuvant therapy) CRC patients with unresectable liver metastases, with WHO performance statuses of 0 to 2. On an outpatient basis, the patients received a treatment regimen consisting of 5-fluorouracil at 1000 mg/m2 and l-Leucovorin at 50 mg/m2 for 5 hours on days 1, 8, 15, and 22 by hepatic arterial infusion plus oral UFT (300 mg/m2) and UZEL (75 mg/body) on days 2-7, 9-14, and 23-28 followed by withdrawal for one week. The cycles were repeated every 5 weeks until disease progression.
A total of 103 cycles of HAI with the UFT/UZEL regimen were administered (median, 5 cycles; range, 6 to 9 cycles). The response rate was 87.5% (14 partial responses and 2 stable diseases). The median progression-free survival rate was 9.2 months, and the median survival time was 22 months. No treatment-related grade 3 or 4 adverse events were observed.
This novel locoregional HAI with an oral UFT/UZEL systemic chemotherapeutic regimen is feasible in an outpatient setting and should be considered as first-line chemotherapy for CRC patients with unresectable liver metastases.
背景/目的：在无法切除肝转移灶的结直肠癌（CRC）患者中，肝动脉灌注（HAI）化疗存在诸多局限性，包括完全缓解率低和肝外复发频繁。因此计划开展一项临床试验，以评估HAI联合口服优福定（UFT）和亚叶酸钙（UZEL）化疗方案在无法切除肝转移灶的CRC患者中的安全性和疗效。
16例无法切除肝转移灶的CRC患者接受了HAI与全身性口服UFT/UZEL同步治疗。符合条件的患者为既往未接受过治疗（辅助治疗除外）、无法切除肝转移灶、世界卫生组织体能状态为0至2级的CRC患者。在门诊环境下，患者接受的治疗方案为：在第1、8、15和22天通过肝动脉灌注给予5-氟尿嘧啶1000mg/m²和左亚叶酸钙50mg/m²，持续5小时，同时在第2 - 7天、9 - 14天和23 - 28天口服UFT（300mg/m²）和UZEL（75mg/体），随后停药1周。每5周重复一个周期，直至疾病进展。
共进行了103个周期的HAI联合UFT/UZEL方案治疗（中位数为5个周期；范围为6至9个周期）。缓解率为87.5%（14例部分缓解，2例病情稳定）。无进展生存期的中位数为9.2个月，总生存期的中位数为22个月。未观察到与治疗相关的3级或4级不良事件。
这种新型的局部HAI联合口服UFT/UZEL全身化疗方案在门诊环境下是可行的，应被视为无法切除肝转移灶的CRC患者的一线化疗方案。
