Alterations in intestinal permeability following the intensified polydrug-chemotherapy IFADIC (ifosfamide, Adriamycin, dacarbazine).

Abstract

The aim of this study was to investigate the severity and time-course of alterations in gastroduodenal and intestinal permeability in relation to nausea/emesis following administration of the highly emetogenic polydrug regimen IFADIC (ifosfamide, Adriamycin, dacarbazine) using a differential lactulose/mannitol absorption (SLM) test. We also assessed the ease of administration and patients' tolerance of the SLM test. The SLM test was performed in seven patients with soft tissue sarcomas on days 1, 3 and 14 of cycle I and cycle III of chemotherapy; seven healthy volunteers served as controls. The degree of correlation between the clinical grade of nausea/emesis according to WHO criteria and gastroduodenal permeability, expressed in terms of urinary sucrose excretion, and intestinal permeability, expressed in terms of the permeability index (urinary lactulose to mannitol permeability ratio), was also assessed. The permeability index values were significantly different (P < or =0.01) on days 1, 3 and 14 during both cycles of chemotherapy. The median permeability index on day 3 was higher (P < =0.01) in patients with nausea/emesis than in those without symptoms. Additionally, the permeability index when nausea was present (day 3) was higher (P < or =0.01) than when nausea/emesis was absent (days 1 and 14). In 59% of patients the increased permeability index on day 3 was accompanied by nausea/emesis of WHO grade 3. Gastroduodenal permeability did not alter consistently following chemotherapy. Our study confirms an acute, transient increase in intestinal permeability following the polydrug regimen IFADIC, accompanied by nausea/emesis of WHO grade 3 in the majority of patients. Normal intestinal permeability was achieved on day 14 in all patients, thus allowing intensified 2-weekly treatment administration. The SLM test may be recommended as a feasible test for the objective assessment of alterations in intestinal permeability following chemotherapy administration.