Irinophore C™, a lipid nanoparticle formulation of irinotecan, abrogates the gastrointestinal effects of irinotecan in a rat model of clinical toxicities

Summary Irinotecan is a water-soluble camptothecin derivative with clinical activity against colorectal and small cell lung cancers and is currently a standard of care therapeutic in the treatment of colorectal cancer in combination with 5-fluorouracil. One of the major clinical issues limiting the use of irinotecan is gastrointestinal toxicity manifested as life-threatening diarrhea which is reported in up to 45 % of treated patients. The studies summarized here tested, in a rat model of irinotecan-associated gastro-intestinal toxicity, whether a lipid nanoparticle formulation of irinotecan, Irinophore C™, mitigated early-onset or late-onset diarrhea when given at doses equivalent to unformulated irinotecan that engenders both early- and late-onset diarrhea. Specifically, rats administered intravenously on two consecutive days with unformulated irinotecan at 170 mg/kg then 160 mg/kg experienced transient early-onset diarrhea after each administration and then experienced significant late-onset diarrhea peaking 4 days after treatment. Irinophore C™ given at the identical dose and schedule did not elicit either early- or late-onset diarrhea in any animals. When Irinophore C™ was combined with 5-fluorouracil there was also no early- or late-onset diarrhea observed. Histopathological analysis of the gastro-intestinal tract confirmed that the effects associated with irinotecan treatment were absent in rats given Irinophore C™ at the identical dose....
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research