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The effects of fluorouracil, epirubicin, and cyclophosphamide (FEC60) on the intestinal barrier function and gut peptides in breast cancer patients: an observational study

Francesco Russo1, Michele Linsalata1, Caterina Clemente1, Benedetta D’Attoma1, Antonella Orlando1, Giovanna Campanella2, Francesco Giotta3 and Giuseppe Riezzo4*

Author Affiliations

1 Laboratory of Experimental Biochemistry, National Institute for Digestive Diseases I.R.C.C.S. “Saverio de Bellis”, Castellana Grotte, Bari, Italy

2 Medical Oncology Unit I.R.C.C.S. “Saverio de Bellis”, Castellana Grotte, Bari, Italy

3 Medical Oncology Unit I.R.C.C.S. “Giovanni Paolo II”, Bari, Italy

4 Laboratory of Experimental Pathophysiology, National Institute for Digestive Diseases I.R.C.C.S. “Saverio de Bellis”, Castellana Grotte, Bari, Italy

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BMC Cancer 2013, 13:56  doi:10.1186/1471-2407-13-56

Published: 4 February 2013



Several GI peptides linked to intestinal barrier function could be involved in the modification of intestinal permeability and the onset of diarrhea during adjuvant chemotherapy. The aim of the study was to evaluate the circulating levels of zonulin, glucagon-like peptide-2 (GLP-2), epidermal growth factor (EGF) and ghrelin and their relationship with intestinal permeability and chemotherapy induced diarrhea (CTD).


Sixty breast cancer patients undergoing an FEC60 regimen were enrolled, 37 patients completed the study. CTD(+) patients were discriminated by appropriate questionnaire and criteria. During chemotherapy, intestinal permeability was assessed by lactulose/mannitol urinary test on day 0 and day 14. Zonulin, GLP-2, EGF and ghrelin circulating levels were evaluated by ELISA tests at five time-points (days 0, 3, 10, 14, and 21).


During FEC60 administration, the lactulose/mannitol ratio was significantly higher on day 14 than at baseline. Zonulin levels were not affected by chemotherapy, whereas GLP-2 and EGF levels decreased significantly. GLP-2 levels on day 14 were significantly lower than those on day 0 and day 3, while EGF values were significantly lower on day 10 than at the baseline. In contrast, the total concentrations of ghrelin increased significantly at day 3 compared to days 0 and 21, respectively. Ten patients (27%) suffered from diarrhea. On day 14 of chemotherapy, a significant increase of the La/Ma ratio occurred in CTD(+) patients compared to CTD(−) patients. With regards to circulating gut peptides, the AUCg of GLP-2 and ghrelin were significantly lower and higher in CTD(+) patients than CTD(−) ones, respectively. Finally in CTD(+) patients a significant and inverse correlation between GLP-2 and La/Ma ratio was found on day 14.


Breast cancer patients undergoing FEC60 showed alterations in the intestinal permeability, which was associated with modifications in the levels of GLP-2, ghrelin and EGF. In CTD(+) patients, a different GI peptide profile and increased intestinal permeability was found in comparison to CTD(−) patients. This evidence deserves further studies for investigating the potentially different intestinal luminal and microbiota conditions.

Trial registration

Clinical trial NCT01382667

Breast cancer; Chemotherapy-induced diarrhea; Epidermal growth factor; Intestinal permeability; Ghrelin; Glucagon-like peptide 2; Gut peptides; Zonulin