Irinotecan: 25 years of cancer treatment

Publication date: Available online 12 August 2019Source: Pharmacological ResearchAuthor(s): Christian BaillyAbstractTwenty-five years ago, the cytotoxic drug irinotecan (IRT) was first approved in Japan for the treatment of cancer. For more than two decades, the IRT prodrug has largely contributed to the treatment of solid tumors worldwide. Nowadays, this camptothecin derivative targeting topoisomerase 1 remains largely used in combination regimen, like FOLFIRI and FOLFIRINOX, to treat metastatic or advanced solid tumors, such as colon, gastric and pancreatic cancers and others. This review highlights recent discoveries in the field of IRT and its derivatives, including analogues of the active metabolite SN38 (such as FL118), the recently approved liposomal form Nal-IRI and SN38-based immuno-conjugates currently in development (such as sacituzumab govitecan). New information about the IRT mechanism of action are presented, including the discovery of a new protein target, the single-stranded DNA-binding protein FUBP1. Significant progress has been made also to better understand and manage the main limiting toxicities of IRT, chiefly neutropenia and diarrhea. The role of drug-induced inflammation and dysbiosis is underlined and strategies to limit the intestinal toxicity of IRT are discussed (use of β-glucuronidase inhibitors, plant extracts, probiotics). The detailed knowledge of the metabolism of IRT has enabled the identification of potential biomarkers to guide patient sel...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research