O'Connell M J, Nagorney D M, Bernath A M, Schroeder G, Fitzgibbons R J, Mailliard J A, Burch P, Bolton J S, Colon-Otero G, Krook J E
Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
J Clin Oncol. 1998 Jul;16(7):2528-33. doi: 10.1200/JCO.1998.16.7.2528.
Extrahepatic metastasis represents a frequent pattern of disease progression when fluorodeoxyuridine (FUDR) is given by the intraarterial route for the treatment of unresectable colorectal liver metastases. Systemic fluorouracil (5-FU) plus leucovorin was added to intrahepatic FUDR to prolong the duration of disease control.
Only patients with colorectal cancer who had evidence of unresectable metastases confined to the liver were eligible. Laparotomy was performed to establish arterial perfusion of the liver. Cycles of intrahepatic FUDR followed by a 1-week rest period then intravenous chemotherapy with 5-FU plus leucovorin were administered until maximal regression of hepatic metastases. Maintenance chemotherapy with 5-FU plus leucovorin was then given until disease progression.
Fifty-seven patients entered this trial; four patients (7%) were ineligible and 13 (23%) did not receive any chemotherapy on study because of findings at laparotomy. The 40 eligible patients who began chemotherapy are included in the statistical analyses. Twenty-five patients (62% of those who received chemotherapy) experienced regression of liver metastases. The median time to tumor progression was 9 months, but only 3% remained progression-free at 24 months. The median survival duration was 18 months. Toxicity was tolerable with no cases of biliary sclerosis. One treatment-related fatality due to sepsis was observed.
Although short-term treatment results appear to be somewhat better than we have previously observed with intrahepatic FUDR alone, the sequential regimen did not have an impact on long-term, progression-free survival in patients with unresectable liver metastases. We are now investigating this regimen as surgical adjuvant therapy in selected patients following hepatic metastasectomy where this aggressive approach might have a greater therapeutic effect in the minimal residual disease setting.
当通过动脉途径给予氟脱氧尿苷（FUDR）治疗不可切除的结直肠癌肝转移时，肝外转移是疾病进展的常见模式。肝内给予FUDR的同时加用全身氟尿嘧啶（5-FU）和亚叶酸以延长疾病控制时间。
仅纳入有证据表明不可切除的转移局限于肝脏的结直肠癌患者。进行剖腹手术以建立肝脏的动脉灌注。给予肝内FUDR周期治疗，随后休息1周，然后进行5-FU加亚叶酸的静脉化疗，直至肝转移灶最大程度消退。然后给予5-FU加亚叶酸维持化疗，直至疾病进展。
57例患者进入该试验；4例患者（7%）不符合入组标准，13例患者（23%）因剖腹手术结果未接受任何研究化疗。开始化疗的40例符合条件的患者纳入统计分析。25例患者（接受化疗患者的62%）肝转移灶出现消退。肿瘤进展的中位时间为9个月，但24个月时只有3%的患者无疾病进展。中位生存时间为18个月。毒性可耐受，无胆汁硬化病例。观察到1例与治疗相关的败血症死亡病例。
尽管短期治疗结果似乎比我们之前单独使用肝内FUDR时观察到的结果稍好，但序贯方案对不可切除肝转移患者的长期无进展生存没有影响。我们目前正在研究该方案作为肝转移瘤切除术后选定患者的手术辅助治疗，在这种微小残留病灶情况下这种积极的方法可能具有更大的治疗效果。
