肝动脉注射氟尿苷和亚叶酸治疗不可切除的结直肠癌肝转移。新的剂量方案及生存情况更新
Hepatic arterial floxuridine and leucovorin for unresectable liver metastases from colorectal carcinoma. New dose schedules and survival update.
作者信息
Kemeny N, Seiter K, Conti J A, Cohen A, Bertino J R, Sigurdson E R, Botet J, Chapman D, Mazumdar M, Budd A J
机构信息
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
出版信息
Cancer. 1994 Feb 15;73(4):1134-42. doi: 10.1002/1097-0142(19940215)73:4<1134::aid-cncr2820730403>3.0.co;2-v.
BACKGROUND
We studied three new dose schedules of hepatic arterial infusion of floxuridine (FUDR) and leucovorin and update survival analysis of a previously reported trial using these drugs by hepatic arterial infusion for patients with hepatic metastases from colorectal carcinoma.
METHODS
Untreated patients with hepatic metastases from colorectal cancer were treated with three dose schedules: Group D, FUDR (0.3 mg/kg/day) and leucovorin (30 mg/m2/day) as a 14-day continuous infusion through an implantable hepatic arterial pump alternating with a 4-week rest period; Group E, a lower dose of FUDR (0.25 mg/kg/day) and leucovorin (30 mg/m2/day) as a 14-day infusion alternating with 2 weeks of saline; and Group F, FUDR (0.3 mg/kg/day) with a lower leucovorin dose (15 mg/m2/day) for 2 weeks followed by a 2-week rest.
RESULTS
In 42 patients with unresectable hepatic metastases, the complete-plus-partial response rate was 56%, with a median survival of 24.2 months. Complete-plus-partial response rates for groups D, E, and F were 30%, 54%, and 75%, respectively. Twelve percent of the 42 patients developed biliary sclerosis; the percentages of patients per group were 17%, 15%, and 6%, respectively. Updated median survival of the original 24 patients treated with FUDR and leucovorin by hepatic arterial infusion and these 42 new patients (66 total) was 28.8 months. One-, two-, three-, four-, and five-year survival rates were 86%, 62%, 31%, 15%, and 7%, respectively.
CONCLUSIONS
Hepatic arterial chemotherapy with FUDR and leucovorin for patients with hepatic metastases from colorectal carcinoma yields a high response rate and 1- and 2-year survivals of 86% and 62%, respectively. Although a lower dose of leucovorin (15 mg/m2) with FUDR produces a high response rate with less toxicity, before larger scale trials are initiated, further investigation is needed to reduce toxicity. A study of hepatic arterial dexamethasone with FUDR and leucovorin has been initiated for this purpose.
背景
我们研究了氟尿苷（FUDR）和亚叶酸钙经肝动脉灌注的三种新剂量方案，并对先前报道的一项使用这些药物经肝动脉灌注治疗结直肠癌肝转移患者的试验进行了生存分析更新。
方法
未接受过治疗的结直肠癌肝转移患者接受三种剂量方案治疗：D组，FUDR（0.3mg/kg/天）和亚叶酸钙（30mg/m²/天）通过植入式肝动脉泵进行14天持续灌注，期间交替4周休息期；E组，较低剂量的FUDR（0.25mg/kg/天）和亚叶酸钙（30mg/m²/天）进行14天灌注，期间交替2周生理盐水灌注；F组，FUDR（0.3mg/kg/天）与较低剂量的亚叶酸钙（15mg/m²/天）联合使用2周，随后休息2周。
结果
42例不可切除肝转移患者的完全缓解加部分缓解率为56%，中位生存期为24.2个月。D组、E组和F组的完全缓解加部分缓解率分别为30%、54%和75%。42例患者中有12%发生了胆汁硬化；每组患者的发生率分别为17%、15%和6%。最初接受FUDR和亚叶酸钙经肝动脉灌注治疗的24例患者以及这42例新患者（共66例）的更新后中位生存期为28.8个月。1年、2年、3年、4年和5年生存率分别为86%、62%、31%、15%和7%。
结论
FUDR和亚叶酸钙经肝动脉化疗治疗结直肠癌肝转移患者的缓解率较高，1年和2年生存率分别为86%和62%。虽然较低剂量的亚叶酸钙（15mg/m²）与FUDR联合使用可产生高缓解率且毒性较小，但在开展大规模试验之前，需要进一步研究以降低毒性。为此已启动一项关于FUDR、亚叶酸钙与肝动脉地塞米松联合使用的研究。
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