A RANDOMIZED TRIAL OF CONTINUOUS INTRAVENOUS VERSUS HEPATIC INTRAARTERIAL FLOXURIDINE IN PATIENTS WITH COLORECTAL-CANCER METASTATIC TO THE LIVER - THE NORTHERN-CALIFORNIA-ONCOLOGY-GROUP-TRIAL
A RANDOMIZED TRIAL OF CONTINUOUS INTRAVENOUS VERSUS HEPATIC INTRAARTERIAL FLOXURIDINE IN PATIENTS WITH COLORECTAL-CANCER METASTATIC TO THE LIVER - THE NORTHERN-CALIFORNIA-ONCOLOGY-GROUP-TRIAL
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DOI：
10.1200/jco.1989.7.11.1646
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发表时间：
1989-11-01
影响因子：
45.3
通讯作者：
LEWIS, BJ
中科院分区：
文献类型：
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作者：
HOHN, DC;STAGG, RJ;LEWIS, BJ
1983年，北方加州肿瘤学小组（NCOG）开展了一项随机试验，通过植入式泵对转移至肝脏的结直肠癌患者进行静脉（IV）与动脉（IA）给药的对比研究。研究目的是比较两个治疗组的肝脏缓解率、至肝脏进展时间和毒性。研究设计允许IV FUDR失败的患者交叉至IA组，这妨碍了有意义的生存期比较分析。仅肝脏转移的患者（N = 143）被随机分配，76例分配至IV组，67例分配至IA组，115例患者（65例IV，50例IA）可完全评价。在IV组的65例患者中，28例在IV FUDR失败后交叉至IA治疗。IV FUDR的剂量限制性毒性是腹泻，而胆汁毒性限制IA FUDR治疗的剂量和持续时间。在以0.3 mg/kg/天的剂量接受IA FUDR治疗的前25名患者中，10名患者发生了放射学上明显的胆管狭窄，3名患者发生了永久性黄疸。随着IA FUDR初始剂量降低至0.2 mg/kg/天，并采取早期剂量降低、治疗中断或因碱性磷酸酶持续升高而终止治疗的政策，仅发生了另外2例严重胆汁毒性病例。然而，50例IA FUDR患者中有26例最终因药物毒性而非疾病进展终止治疗。与全身灌注相比，肝动脉灌注可显著增强FUDR对结直肠癌肝转移的抗肿瘤活性。虽然胆汁毒性是这种治疗形式最严重的限制，但通过仔细监测肝酶和早期减少剂量，通常可以避免胆管狭窄和黄疸。
In 1983, the Northern California Oncology Group (NCOG) instituted a randomized trial of intravenous (IV) versus inraarterial (IA) floxuridine (FUDR) administered via an implantable pump for patients with colorectal cancer metastatic to the liver. The study objectives were to compare the hepatic response rate, time to hepatic progression, and toxicity for the two treatment arms. The study design, which allowed patients failing IV FUDR to crossover to the IA arm, prevents a meaningful comparative analysis of survival. Patients with liver-only metastases (N = 143) were randomized, 76 to the IV arm and 67 to the IA arm, and 115 patients (65 IV, 50 IA) were fully evaluable. Of the 65 patients in the IV arm, 28 crossed over to IA treatment after failing IV FUDR. The dose-limiting toxicity of IV FUDR was diarrhea, whereas biliary toxicity limited both the dose and duration of IA FUDR therapy. Of the first 25 patients treated with IA FUDR at a dose of .3 mg/kg/day, 10 developed radiographically evident biliary strictures, and three developed permanent jaundice. With reduction of the initial IA FUDR dose to .2 mg/kg/day, and adoption of a policy of early dosage reduction, treatment interruption, or termination of therapy for persistent elevations in alkaline phosphatase, only two further cases of serious biliary toxicity occurred. However 26 of the 50 IA FUDR patients ultimately had therapy terminated because of drug toxicity rather than disease progression. When compared with systemic infusion, infusion into the hepatic artery greatly enhanced the antitumor activity of FUDR against colorectal liver metastases. Although biliary toxicity is the most serious limitation of this form of therapy, biliary stricture and jaundice usually can be averted through careful monitoring of liver enzymes and early dosage reduction.