Patient preference and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin:: a randomised crossover trial in advanced colorectal cancer
Patient preference and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin:: a randomised crossover trial in advanced colorectal cancer
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DOI：
10.1016/s0959-8049(01)00371-9
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发表时间：
2002-02-01
影响因子：
8.4
通讯作者：
Fumoleau, P
中科院分区：
文献类型：
--
作者：
Borner, MM;Schöffski, P;Fumoleau, P
本研究的目的是确定患者对口服UFT/亚叶酸素（LV）或静脉注射（i.v.）的偏好。5-氟尿嘧啶(5-FU)/LV化疗在转移性结直肠癌中的应用以及5-FU暴露与这两种治疗方案的比较共有37名先前未经治疗的晚期结直肠癌患者被随机分组，开始治疗时口服UFT 300 mg/m(2)/天+口服LV 90 mg/天，每5周28天，或静脉注射5- fu 425 mg/m(2)/天+ LV 20 mg/m(2)/天，每4周5天。对于第二个治疗周期，患者被交叉到替代治疗方案。在第一个治疗周期之前和第二个治疗周期之后，患者被要求完成一份治疗偏好问卷（TPQ）。5- fu的药代动力学通过在UFT组的第8、15、22和28天以及静脉注射5- fu组的第1和5天采血来测定。36例患者符合条件。84%的患者更喜欢口服UFT而不是静脉注射5-FU，在经历了两种治疗方式后，患者表示在家服药，口腔炎和腹泻较少，药丸而不是注射是他们首选的最重要原因。UFT给药后5-FU的血药浓度曲线下面积（AUC）在第8天为113 muM x min，第15天为114，第28天为98，峰值水平（Cmax）为1.2。1.3和1.0 muM。分别。5- fu /LV疗程的AUC为第1天3083 muM x min，第5天3809 （P=0.002）。Cmax分别为170.1和196.2 muM (P= 0.06)，清除率分别为2.6和1.9 l/min。分别(P = 0.002)。转移性结直肠癌患者显然更倾向于口服化疗而不是静脉化疗。这种选择主要受便利性和毒性考虑的影响。尽管与口服UFT相比，静脉注射5-FU可导致更高的峰值5-FU浓度和AUC值，但在比较口服UFT/LV与静脉注射5-FU/LV的大型随机研究中发现，静脉注射5-FU的药代动力学优势似乎主要转化为更高的毒性，但在毒性和患者偏好方面，口服UFT/LV优于静脉注射5-FU/LV，并导致5-FU暴露时间延长。这与持续静脉注射5-FU治疗相当。(C) 2002 Elsevier Science Ltd.版权所有。
The aim of this study was to determine the patient's preference for oral UFT/leucovorin (LV) or intravenous (i.v.) 5-fluorouracil (5-FU)/LV chemotherapy in metastatic colorectal cancer and to compare 5-FU exposure with these two treatment options. A total of 37 previously untreated patients with advanced colorectal cancer were randomised to start treatment with either oral UFT 300 mg/m(2)/day plus oral LV 90 mg/day for 28 days every 5 weeks or i.v. 5-FU 425 mg/m(2)/day plus LV 20 mg/m(2)/day for 5 days every 4 weeks. For the second treatment cycle, patients were crossed-over to the alternative treatment regimen. Prior to the first and after the second therapy cycle, patients were required to complete a therapy preference questionnaire (TPQ). The pharmacokinetics of 5-FU were determined by taking blood samples on days 8, 15 or 22 and 28 for UFT and on days I and 5 for i.v. 5-FU. 36 patients were eligible. 84% of the patients preferred oral UFT over i.v. 5-FU, After having experienced both treatment modalities, patients indicated taking the medication at home, less stomatitis and diarrhoea, and pill over injection as the most important reasons for their preference. The area under the plasma concentration curve (AUC for 5-FU after UFT administration was 113 muM x min on day 8, 114 on day 15 and 98 on day 28, the peak levels (Cmax) were 1.2. 1.3 and 1.0 muM. respectively. The AUC for the 5-FU/LV courses was 3083 muM x min for day 1 and 3809 for day 5 (P=0.002). The Cmax was 170.1 and 196.2 muM (P= 0.06) and the clearance 2.6 and 1.9 l/min. respectively (P=0.002). Patients with metastatic colorectal cancer clearly preferred oral over i.v. chemotherapy treatment. This choice was most importantly influenced by convenience and toxicity considerations. Although i.v. bolus 5-FU leads to higher peak 5-FU concentrations and AUC values compared with oral UFT, this pharmacokinetic advantage of i.v. 5-FU seems to translate mainly into higher toxicity as seen in large randomised studies comparing oral UFT/LV with i.v. 5-FU/LV, Oral UFT/LV compares favourably with i.v. 5-FU/LV in terms of toxicity and patient's preference and leads to prolonged 5-FU exposure. which is comparable to continuous i.v. 5-FU treatment. (C) 2002 Elsevier Science Ltd. All rights reserved.