口服谷氨酰胺预防氟尿嘧啶所致肠道毒性：一项双盲、安慰剂对照的随机试验。
Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: a double blind, placebo controlled, randomised trial.
作者信息
Daniele B, Perrone F, Gallo C, Pignata S, De Martino S, De Vivo R, Barletta E, Tambaro R, Abbiati R, D'Agostino L
机构信息
Divisione di Oncologia Medica B, Istituto Nazionale Tumori, Napoli, Italy.
出版信息
Gut. 2001 Jan;48(1):28-33. doi: 10.1136/gut.48.1.28.
BACKGROUND
5-Fluorouracil (FU) in association with folinic acid (FA) is the most frequently used chemotherapeutic agent in colorectal cancer but it often causes diarrhoea. Animal and human studies suggest that glutamine stimulates intestinal mucosal growth.
AIM
To determine if oral glutamine prevents changes in intestinal absorption (IA) and permeability (IP) induced by FU/FA.
METHODS
Seventy chemotherapy naive patients with colorectal cancer were randomly assigned to oral glutamine (18 g/day) or placebo before the first cycle of FU (450 mg/m(2)) and FA (100 mg/m(2)) administered intravenously for five days. Treatment was continued for 15 days, starting five days before the beginning of chemotherapy. IA (D-xylose urinary excretion) and IP (cellobiose-mannitol test) were assessed at baseline and four and five days after the end of the first cycle of chemotherapy, respectively. Patients kept a daily record of diarrhoea, scored using the classification system of the National Cancer Institute (Bethesda, Maryland, USA). Duration of diarrhoea was recorded and the area under the curve (AUC) was calculated for each patient.
RESULTS
Baseline patient characteristics and basal values of IP and IA tests were similar in the two arms. After one cycle of chemotherapy, the reduction in IA (D-xylose absorption) was more marked in the placebo arm (7.1% v 3. 8%; p=0.02); reduction of IP to mannitol was higher in the placebo arm (9.2% v 4.5%; p=0.02); and urinary recovery of cellobiose was not different between the study arms (p=0.60). Accordingly, the cellobiose-mannitol ratio increased more in the placebo arm (0.037 v 0.012; p=0.04). Average AUC of diarrhoea (1.9 v 4.5; p=0.09) and average number of loperamide tablets taken (0.4 v 2.6; p=0.002) were reduced in the glutamine arm.
CONCLUSIONS
Glutamine reduces changes in IA and IP induced by FU and may have a protective effect on FU induced diarrhoea.
背景
5-氟尿嘧啶（FU）联合亚叶酸（FA）是结直肠癌最常用的化疗药物，但常引起腹泻。动物和人体研究表明，谷氨酰胺可刺激肠黏膜生长。
目的
确定口服谷氨酰胺是否能预防FU/FA诱导的肠道吸收（IA）和通透性（IP）变化。
方法
70例初治结直肠癌患者在接受为期5天的静脉注射FU（450mg/m²）和FA（100mg/m²）的第一个周期化疗前，随机分为口服谷氨酰胺（18g/天）组或安慰剂组。治疗持续15天，从化疗开始前5天开始。分别在基线时以及化疗第一个周期结束后第4天和第5天评估IA（D-木糖尿排泄）和IP（纤维二糖-甘露醇试验）。患者每天记录腹泻情况，使用美国国立癌症研究所（马里兰州贝塞斯达）的分类系统进行评分。记录腹泻持续时间，并计算每位患者的曲线下面积（AUC）。
结果
两组患者的基线特征以及IP和IA试验的基础值相似。化疗一个周期后，安慰剂组IA（D-木糖吸收）的降低更为明显（7.1%对3.8%；p=0.02）；安慰剂组对甘露醇的IP降低更高（9.2%对4.5%；p=0.02）；研究组间纤维二糖的尿回收率无差异（p=0.60）。因此，安慰剂组纤维二糖-甘露醇比值增加更多（0.037对0.012；p=0.04）。谷氨酰胺组腹泻的平均AUC（1.9对4.5；p=0.09）和服用洛哌丁胺片的平均数量（0.4对2.6；p=0.002）降低。
结论
谷氨酰胺可减少FU诱导的IA和IP变化，可能对FU诱导的腹泻有保护作用。
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