Intestinal permeability, vitamin A absorption and serum alpha-tocopherol during therapy with gefitinib.

Measurement of intestinal permeability represents one of the potential methods of noninvasive laboratory assessment of gastrointestinal toxicity of anticancer therapy. We have assessed intestinal permeability (by measuring absorption of lactulose, mannitol, and xylose), vitamin A absorption and serum alpha-tocopherol in patients with non-small cell lung carcinoma or head and neck carcinomas treated with gefitinib. Lactulose, mannitol and xylose were determined by capillary gas chromatography, and retinol, alpha-tocopherol, retinyl stearate and retinyl palmitate were determined by high-performance liquid chromatography. Compared to healthy controls, patients had significantly increased lactulose/mannitol ratio and lower postprandial retinyl palmitate and retinyl stearate concentrations. Compared with pre-treatment values, xylose absorption was decreased and lactulose/mannitol and lactulose/xylose ratios were increased during the therapy. A significant decrease of serum alpha-tocopherol was evident throughout the course of therapy. In contrast, only minor alterations of vitamin A absorption were observed. In conclusion, an alteration in intestinal permeability reflected in increased lactulose/mannitol and lactulose/xylose ratios was observed during gefitinib therapy. Potential association between decreased serum alpha-tocopherol concentrations and the toxicity of gefitinib therapy should be further investigated.