Background and importance Irinotecan’s antineoplastic activity, as well as its safety, depends on the action of its active metabolite, SN-38, which is inactivated by UDP-glucuronosyltransferase (UGT), an enzyme encoded by the UGT1A1 gene. The presence of the *28 allele decreases the elimination of SN-38. Some studies have shown the possibility of using doses of irinotecan higher than 180 mg/m2 in patients with the UGT1A1*1/*1 and *1/*28 genotypes.
Aim and objectives To analyse published data about the use of a higher dose than 180 mg/m2 of irinotecan and its relationship with the efficacy and safety in metastatic colorectal cancer (mCRC) patients with the UGT1A1*1/*1 and *1/*28 genotypes treated with the FOLFIRI scheme.
Material and methods A systematic review was carried out in Medline. The quest was done for articles published up to November 2020. MeSH terms used were: irinotecan and UGT1A1. Methods used were based on those recommended according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched for randomised clinical trials (RCTs) and observational studies. Four reviewers independently assessed the eligibility of each study. To assess the methodological quality of the RCT and the observational studies included, the Jadad and the Newcastle-Ottawa (NOS) scales were used, respectively.
Results Search strategy reported 595 references, of which 13 were selected for analysis, 7 (53.8%) evaluating both efficacy and safety and 6 (46.2%) only safety. In relation to the studies that evaluated efficacy and safety, 6 (85.7%) were in favour of increasing the dose in terms of objective response rate (ORR) and progression-free survival (PFS), and even in one of them, in overall survival (OS). Studies evaluating safety suggested that doses of irinotecan greater than 180 mg/m2 are tolerated by most UGT1A1*1/*1 and *1/*28 patients. Of all the studies analysed, only one of them showed greater toxicity (grade ≥3) in the group with increased doses of irinotecan compared to the control group.
Conclusion and relevance The present systematic review shows the convenience of assessing the irinotecan dose adjustment within the FOLFIRI scheme based on UGT1A1 polymorphisms, with a potential increase in the probabilities of an adequate clinical response.
Conflict of interest No conflict of interest
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