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

Anticancer Drugs. 2001 Aug;12(7):619-25. doi: 10.1097/00001813-200108000-00009.


Various clinical and laboratory parameters have been investigated for their ability to predict toxicity arising from the use of the anticancer drug, irinotecan (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 describe one case of a patient with metastatic colorectal cancer treated with a single 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 compromised SN-38 conjugation. Plasma samples were analyzed by reversed-phase high-performance liquid chromatography assay for CPT-11 and its metabolites 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 raised (11- to 60-fold expected). Additionally the estimated terminal half-lives 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 drug excretion through both hepatic and renal routes.

Publication types

  • Case Reports

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / secondary
  • Adenomatous Polyposis Coli Protein / metabolism
  • Antineoplastic Agents, Phytogenic / adverse effects*
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Camptothecin / adverse effects*
  • Camptothecin / analogs & derivatives*
  • Camptothecin / metabolism
  • Camptothecin / pharmacokinetics
  • Cecal Neoplasms / drug therapy
  • Cecal Neoplasms / metabolism
  • Cecal Neoplasms / pathology
  • Chemical and Drug Induced Liver Injury*
  • Humans
  • Irinotecan
  • Kidney / drug effects*
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / metabolism
  • Liver / drug effects*
  • Liver Diseases / metabolism
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary
  • Male
  • Middle Aged
  • Topoisomerase I Inhibitors


  • Adenomatous Polyposis Coli Protein
  • Antineoplastic Agents, Phytogenic
  • Topoisomerase I Inhibitors
  • Irinotecan
  • Camptothecin