Irinotecan toxicity

The toxicity of irinotecan is predictable, manageable and nonadditive in the majority of patients; however, with its increasing use alone and in combination with other agents and modalities, the recognition and control of these adverse effects remain a clinical challenge. Major efforts over the last several years have focused not only on adding fluoropyrimidines and epidermal growth factor receptor inhibitors to irinotecan, but also investigating factors that account for interindividual differences in toxicities.

The association of uridine diphosphoglucuronosyl transferase 1A polymorphisms with increased irinotecan-induced diarrhea and neutropenia, the dose adjustment of irinotecan in the setting of hepatic dysfunction and the observation that 'chemo' liver can develop in the neoadjuvant colorectal cancer setting are recently reported. Also, data from the Sandostatin LAR Depot Trial for the Optimum Prevention of chemotherapy-induced diarrhea support the 30 mg dose of octreotide LAR to manage the condition.

Recent evidence demonstrates that patients with hepatic insufficiency, uridine diphosphoglucuronosyl transferase 1A polymorphisms (e.g. 1A128 homozygotes and heterozygotes), are at greater risk for irinotecan-induced toxicity. Adjusting irinotecan's dose to the degree of hepatic insufficiency is now established. While 'chemo' liver is not specific to irinotecan, its occurrence influences strategies for treating advanced colorectal cancer. Finally, controlling chemotherapy-induced diarrhea with 30 mg of octreotide LAR is adequate for most patients.