Kemeny N, Conti J A, Sigurdson E, Cohen A, Seiter K, Lincer R, Niedzwiecki D, Botet J, Chapman D, Costa P
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Cancer. 1993 Mar 15;71(6):1964-71. doi: 10.1002/1097-0142(19930315)71:6<1964::aid-cncr2820710607>3.0.co;2-t.
Most patients with colorectal carcinoma metastatic to the liver have relapses after surgical resection of hepatic metastases with failures divided equally between hepatic and extrahepatic sites. A pilot study was begun using a regimen combining intrahepatic floxuridine (FUDR) and systemic 5-fluorouracil (5-FU) and leucovorin (LV) to determine its safety and efficacy.
Because this was a pilot study, 21 patients with unresectable hepatic metastases from colorectal carcinoma were treated to assess the regimen's toxicity. Eight patients had liver metastases that were resected completely; then they received treatment. FUDR was given by hepatic arterial pump through a 14-day continuous infusion at 0.25 mg/kg/day. Systemic therapy consisted of LV 200 mg/m2 and 5-FU 280 mg/m2 using a bolus dose of 5-FU for 5 days with escalation of the 5-FU dose in separate patient cohorts. The maximally tolerated 5-FU dose was 325 mg/m2.
The median survival in the 21 unresectable patients was 16 months with a partial response rate of 56% (10 of 18 evaluable patients; 95% confidence interval, 38-79%). The major systemic toxicity was diarrhea, Grade 3 or 4, in 54% of patients being treated in the 4-week regimen and 19%, in the 5-week regimen. The level of hepatic toxicity was similar to that in previous studies using intrahepatic chemotherapy alone, i.e., 48% of patients had a 200% increase in alkaline phosphatase levels and 10% had bilirubin elevations of more than 3.0 mg/dl (one patient had documented biliary sclerosis). All eight patients treated with adjuvant therapy were alive without disease after a median follow-up of 23 months.
Systemic 5-FU and LV can be combined safely with intraarterial FUDR without loss of efficacy or increased biliary toxicity. Eight patients treated with this regimen as adjuvant therapy after liver metastasis resection were alive and disease-free after a median follow-up of 23 months.
大多数发生肝转移的结直肠癌患者在手术切除肝转移灶后会复发，肝内和肝外部位的复发几率相同。一项初步研究开始采用肝内氟尿苷（FUDR）、全身应用5-氟尿嘧啶（5-FU）和亚叶酸（LV）的联合方案，以确定其安全性和疗效。
由于这是一项初步研究，21例无法切除的结直肠癌肝转移患者接受治疗以评估该方案的毒性。8例患者的肝转移灶被完全切除，然后接受治疗。FUDR通过肝动脉泵以0.25mg/kg/天的剂量持续输注14天。全身治疗包括LV 200mg/m²和5-FU 280mg/m²，5-FU采用大剂量推注，持续5天，不同患者队列中的5-FU剂量逐步增加。最大耐受的5-FU剂量为325mg/m²。
21例无法切除的患者的中位生存期为16个月，部分缓解率为56%（18例可评估患者中的10例；95%置信区间，38-79%）。主要的全身毒性为腹泻，4周方案治疗的患者中有54%为3级或4级腹泻，5周方案治疗的患者中有19%为3级或4级腹泻。肝毒性水平与既往单独使用肝内化疗的研究相似，即48%的患者碱性磷酸酶水平升高200%，10%的患者胆红素升高超过3.0mg/dl（1例患者有记录的胆汁硬化）。所有8例接受辅助治疗的患者在中位随访23个月后均无病存活。
全身应用5-FU和LV可安全地与动脉内FUDR联合使用，而不会降低疗效或增加胆汁毒性。8例在肝转移灶切除后接受该方案辅助治疗的患者在中位随访23个月后均无病存活。
