Experimental assessment of chemotherapy-induced early intestinal damage in colon cancer the lactulose-mannitol permeability test.
OBJECTIVE
Although chemotherapy plays an important role in the management and cure of cancer, it has undesiderable side effects mostly affecting the bone marrow and gastrointestinal tract, which greatly limit patient compliance and treatment efficacy.


METHODS
The lactulose-mannitol test was used to assess intestinal mucosa damage 48 hours after the end of the first adjuvant chemotherapy cycle with 5-fluorouracil (5-FU) and levamisole in 12 patients with colon cancer. Fifteen age- and sex-matched subjects were studied as controls. The excreted amount of lactulose and mannitol was expressed as the percentage of the administered doses recovered in the urine as well as their ratio.


RESULTS
The percent urinary recovery of lactulose was significantly (P < 0.001) higher in colon cancer patients (1.1 +/- 0.5%) than in the control group (0.3 +/- 0.03%), whereas the mannitol recovery was only slightly reduced in the former. As a result, the lactulose/mannitol excretion ratio was significantly (P < 0.001) higher in colon cancer patients (0.07 +/- 0.03) than in the control group (0.01 +/- 0.01).


CONCLUSIONS
As assessed by the lactulose-mannitol test, the combined chemotherapy regimen with 5-FU and levamisole affects mainly the barrier function of the intestinal mucosa rather than its absorption capacity. The toxic effect seems to be attributable to the 5-FU molecule rather than to levamisole. The lactulose-mannitol test is a simple, safe and reliable tool to evaluate chemotherapy-induced early damage to the intestinal epithelium, in particular when new kinds of substances are being administered. Its use in clinical practice seems appropriate to establish the correct timing of drug administration, thereby enhancing treatment efficacy and improving patient compliance.
Sukkar
Samir Giuseppe
SG
Clinical Nutrition Unit, S Martino University Hospital, Genoa, Italy. samir.sukkar@hsanmartino.liguria.it
Schenone
Emanuela
E
Foppiani
Luca
L
Nobile
Maria Teresa
MT
D000284:Administration, Oral; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D002199:Capillary Permeability / Q000187:drug effects; D016022:Case-Control Studies; D017024:Chemotherapy, Adjuvant; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects; D005765:Gastrointestinal Agents / Q000493:pharmacokinetics / Q000652:urine; D006801:Humans; D007275:Injections, Intravenous; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects; D007792:Lactulose / Q000493:pharmacokinetics / Q000652:urine; D007978:Levamisole / Q000009:adverse effects; D008297:Male; D008353:Mannitol / Q000493:pharmacokinetics / Q000652:urine; D008875:Middle Aged; D012811:Sigmoid Neoplasms / Q000188:drug therapy* / Q000601:surgery
D005765:Gastrointestinal Agents; D007978:Levamisole; D008353:Mannitol; D007792:Lactulose; D005472:Fluorouracil