Objective:

The purpose of this systematic review is to analyze the published data on the efficacy and safety of doses higher than 180 mg/m2 of irinotecan recommended in the drug’s summary of product characteristics in metastatic colorectal cancer patients with genotypes UGT1A1 *1/*1 or *1/*28 who are treated with the FOLFIRI regimen.

Method:

A systematic review of the literature was carried out in Medline and Embase searching for articles published up to December 2021. The methods used were based on the recommendations of the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) statement. The criteria for the inclusion of studies were previously defined based on the two secondary goals addressed in this review: 1) To analyze the magnitude of the differences in clinical responses and 2) To study the magnitude of the differences in adverse effects of irinotecan at high doses, as compared to the doses described in the summary of product characteristics corresponding to the FOLFIRI regimen in patients with metastatic colorectal cancer with genotypes UGT1A1 *1/* 1 or *1/*28.

Results:

The search yielded a total of 985 references, of which 13 were selected for analysis. Seven evaluated both efficacy and safety and six only safety. With regard to the studies that evaluated both efficacy and safety, six out of seven (85.7%) were in favor of increasing irinotecan dose according to the objective response rate and progressionfree survival. Two of them even recommended dose increases based on overall survival. Irinotecan safety studies suggest that doses higher than 180 mg/m2 are tolerated by most UGT1A1 *1/*1 and *1/*28 patients.

Conclusions:

The present systematic review shows the advisability of considering adjusting the dose of irinotecan when used as part of the FOLFIRI regimen based on the polymorphisms of the UGT1A1 gene as this may increase the likelihood of an adequate clinical response.