The effect of oral glutamine on 5-fluorouracil/leucovorin-induced mucositis/stomatitis assessed by intestinal permeability test.
OBJECTIVE
Systemic chemotherapy may damage gastrointestinal epithelium. Mucositis is associated with increased intestinal permeability (IP). It is known that IP test with chromium 51-ethylene diaminetetra-acetate (51Cr-EDTA) is a useful tool to assess the mucositis. Oral glutamine supplements (OGS) may have a role in the prevention of chemotherapy-induced mucositis/stomatitis. The aim of this study was to characterize the relationship between the urinary excretion of 51Cr-EDTA and the severity of mucositis, and the effect of OGS on 5-fluorouracil/leucovorin (FU/LV)-induced mucositis/stomatitis.


METHODS
Fifty-one patients with advanced or metastatic cancer received FU/LV chemotherapy. The control group included 18 healthy volunteers. IP was assessed via the measurement of 51Cr-EDTA urinary excretion after oral challenge, on days 7 after the discontinuation of chemotherapy. Of the 51 patients, 22 patients received OGS (30 g/day) and 29 received only best supportive care (BSC). Glutamine supplementation continued for 15 days. It was initiated at least 3 days before the beginning of chemotherapy. Mucositis/stomatitis was graded according to version 3.0 of the Common Terminology Criteria for Adverse Events.


RESULTS
In the chemotherapy group, the median (25 percentile, 75 percentile) IP test score was significantly higher than those of the control group [6.78% (4.63, 10.66) vs. 2.17% (1.38, 2.40), P<0.001]. The severity of stomatitis was significantly correlated with IP test scores (r=0.898, P<0.001). In the OGS group, the median IP test score was significantly lower than that of the BSC group [4.69% (3.10, 6.48) vs. 8.54% (6.48, 15.31), P<0.001]. A mucositis/stomatitis of grade 2-4 was observed in two patients of the OGS group (9%), and in 11 patients (38%) in the BSC group (P<0.001).


CONCLUSIONS
The IP test may be a useful tool in the evaluation of mucositis/stomatitis. OGS may exert a protective effect on FU/LV-induced mucositis/stomatitis. Further studies, however, will be necessary to define the role of glutamine supplementation in FU/LV-induced mucositis/stomatitis.
Choi
Kwon
K
Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 110-746, Republic of Korea.
Lee
Seung Sei
SS
Oh
Suk Joong
SJ
Lim
Seong Yong
SY
Lim
Si Young
SY
Jeon
Woo Kyu
WK
Oh
Tae Yun
TY
Kim
Jeong Wook
JW
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002860:Chromium Radioisotopes; D004492:Edetic Acid / Q000652:urine*; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D005973:Glutamine / Q000494:pharmacology*; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control; D009369:Neoplasms / Q000188:drug therapy; D010539:Permeability / Q000187:drug effects*; D012720:Severity of Illness Index; D013280:Stomatitis / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D002860:Chromium Radioisotopes; D005973:Glutamine; D004492:Edetic Acid; D002955:Leucovorin; D005472:Fluorouracil