Phase I clinical and pharmacokinetic study of leucovorin and infusional hepatic arterial fluorouracil.
Phase I clinical and pharmacokinetic study of leucovorin and infusional hepatic arterial fluorouracil.
复制标题
亚叶酸和肝动脉输注氟尿嘧啶的 I 期临床和药代动力学研究。
DOI：
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发表时间：
1995
影响因子：
45.3
通讯作者：
I. Taylor
中科院分区：
文献类型：
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作者：
D. Kerr;J. Ledermann;C. McArdle;J. Buckels;J. Neoptolemos;M. Seymour;J. Doughty;J. Budden;I. Taylor
目的
1993年10月至1994年6月进行了一项I期和药代动力学试验，以确定肝动脉输注（HAI）氟尿嘧啶（5-FU）和静脉注射（IV）亚叶酸（亚叶酸; FA）治疗结直肠癌肝转移患者的最大耐受剂量。
患者和方法
43例患者接受了310个疗程的HAI化疗，每2周给药48小时以上。该方案包括FA 200 mg/m2 IV输注2小时，随后负荷剂量5-FU 400 mg/m2 HAI输注15分钟，随后5-FU输注22小时，剂量范围为0.8 - 1.84 g/m2，第2天化疗相同。进行药代动力学研究以确定5-FU的峰值和稳态血浆浓度（Css）。
结果
重度腹泻以及心脏和神经系统毒性在1.84 g/m2时具有剂量限制性。该方案22小时部分的推荐剂量为1.6 g/m2，与可耐受毒性相关。在推荐的方案中，5-FU的Css为2.2 +/- 0.8 mumol/L，与传统的IV 5-FU方案相比，这是有利的。在30例可评估缓解的患者中，有4例完全缓解和7例部分缓解，12例疾病稳定和7例疾病进展，均在治疗3个月（即6个周期）后报告。
结论
已确定5-FU和FA联合方案用于结直肠癌肝转移患者的区域化疗。达到的5-FU全身水平与使用相同5-FU和FA方案的常规IV de Gramont方案相似，这意味着该化疗方案具有两全其美的优势，即在向靶器官输送高药物浓度方面具有区域优势，同时对肝外微转移有足够的全身覆盖。
PURPOSE
A phase I and pharmacokinetic trial was performed between October 1993 and June 1994 to determine the maximum-tolerated dose of hepatic arterial infusion (HAI) of fluorouracil (5-FU) and intravenous (IV) leucovorin (folinic acid; FA) in patients with hepatic metastases from colorectal cancer.
PATIENTS AND METHODS
Forty-three patients received 310 courses of HAI chemotherapy administered over 48 hours every 2 weeks. The regimen consisted of FA 200 mg/m2 by IV infusion over 2 hours, followed by a loading dose of 5-FU 400 mg/m2 by HAI over 15 minutes, followed by a 22-hour infusion of 5-FU at doses ranging from 0.8 to 1.84 g/m2, with identical chemotherapy on day 2. Pharmacokinetic studies were performed to determine peak and steady-state plasma concentrations (Css) of 5-FU.
RESULTS
Severe diarrhea and cardiac and neurologic toxicity were dose-limiting at 1.84 g/m2. The recommended dose for the 22-hour component of the schedule was 1.6 g/m2 and was associated with tolerable toxicity. A Css of 2.2 +/- 0.8 mumol/L for 5-FU was achieved on the recommended schedule, which compares favorably with conventional IV 5-FU regimens. Among 30 patients assessable for response, there were four complete responses and seven partial responses, and 12 patients with stable disease and seven with progressive disease, reported after 3 months (ie, six cycles) of therapy.
CONCLUSION
A regimen that combines 5-FU and FA has been identified for regional chemotherapy in patients with hepatic metastases from colorectal cancer. The systemic levels of 5-FU achieved are similar to the conventional IV de Gramont regimen using an identical schedule of 5-FU and FA, which implies that this chemotherapy has the best of both worlds, ie, a regional advantage in delivering high drug concentrations to the target organ with adequate systemic cover for extrahepatic micrometastases.
影响因子：
45.3
作者：
HOHN, DC;STAGG, RJ;LEWIS, BJ
通讯作者：
LEWIS, BJ