Toxicity of irinotecan (CPT-11) and hepato-renal dysfunction

Various clinical and laboratory parameters have been Investigated for their ability to predict toxicity arising from the use of the anticancer drug, I rinotecan (CPT-11). In particular, patients deficient in the conjugation of SN-38, a metabolite of CPT-11, are known to be at greater risk. We describ e one case of a patient with metastatic colorectal cancer treated with a si ngle dose of CPT-11 at 125 mg/m(2). Although this patient lacked any known predictive factors for toxicity, he experienced severe side-effects several days later. We hypothesized that the toxicity in this patient was due to c ompromised SN-38 conjugation. Plasma samples were analyzed by reversed-phas e high-performance liquid chromatography assay for CPT-11 and its metabolit es at 96, 144, 168,192 and 288 h post-administration. We observed that the concentrations of both the parent drug and its metabolites were markedly ra ised (11- to 60-fold expected). Additionally the estimated terminal half-li ves were 1.5-7 times those expected (29.5,101, 39.6 and 41.8 h for CPT-11, APC, SN-38G and SN-38, respectively). We conclude that the toxicity in this patient was not caused by deficient SN-38 conjugation, but by decreased dr ug excretion through both hepatic and renal routes. [(C) 2001 Lippincott Wi lliams & Wilkins.].