Clinical mucositis and intestinal permeability abnormalities in metastatic colorectal cancer patients treated with irinotecan and 5-fluoruracil.

Abstract

e14183 Background: The comprehension of the mechanisms involved in the adverse events of the cytotoxic drugs available to treat metastatic colorctal cancer (CRC) is necessary to improve their efficacy and safety. The irinotecan, fluoruracil and folinic acid (IFL) bolus regimen have as its major toxicity issue the complex and multi-mediated gastrointestinal mucositis. Nevertheless, it is difficult to obtain a reliable measurement of the intestinal abnormalities and functional consequences caused by intestinal mucositis, as almost all the clinical data available are reported on a patient symptoms-based scale analysis. Methods: With the lactulose/ mannitol permeability test as the experimental platform, we did a prospective case control study with 25 metastatic CRC patients treated with first line IFL. The primary end point was to compare (Wilcoxon test) the lactulose/ mannitol permeability test before the treatment and the same patients tests at the 15th and 29th day of the first IFL cycle. Blood samples of the same individuals were obtained before the treatment and at 15th day of their first IFL cycle to compare the ELISA serum levels of potentially involved cytokines (TNFα, IL-1β, IL-6, IL-18, IL-18bp e IL-33) (paired t-test). Results: In contrast with the pretreatment controls, the lactulose/ mannitol ratio was significantly (p<0,05) increased at the D15 and D29 in patients taking the first IFL cycle. The mannitol excretion rate was also decreased (p<0,05) at the 29th day. This abnormalities also reserve significant (p<0,05 – Spearman coeficient) correlation with the diarrhea and abdominal pain symptoms (NCI-CTC version 4.0) scale reported by the patients. Otherwise, it has not been possible to demonstrate serum levels differences of the addressed cytokines before and after the treatment. Conclusions: The lactulose/ mannitol permeability test is an objective and reliable tool to measure intestinal permeability abnormalities secondary to gastrointestinal mucositis caused by IFL to metastatic CRC patients.This non-invasive test could bring more objetctive measurement of the functional consequences of this limiting toxicity.