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The results indicate that UGT1A1*28 polymorphism is of some relevance to toxicity; however, it is less important than discussed in previous smaller trials. In particular, the possibility of a dose reduction for irinotecan in patients with a UGT1A1*28 polymorphism is not supported by the result of this analysis.

We propose that UGT1A variants additional to UGT1A1*28 might improve the prediction of the outcome of colorectal cancer patients treated with FOLFIRI. A UGT1A haplotype-based approach might be an efficacious strategy to achieve treatment individualization of FOLFIRI.

Despite scientific and clinical advances in the field of pharmacogenomics (PGx), application into routine care remains limited. Opportunely, several implementation studies and programs have been initiated over recent years. This article presents an overview of these studies and identifies current research gaps. Importantly, one such gap is the undetermined collective clinical utility of implementing a panel of PGx-markers into routine care, because the evidence base is currently limited to specific, individual drug-gene pairs. The Ubiquitous Pharmacogenomics (U-PGx) Consortium, which has been funded by the European Commission's Horizon-2020 program, aims to address this unmet need. In a prospective, block-randomized, controlled clinical study (PREemptive Pharmacogenomic testing for prevention of Adverse drug REactions [PREPARE]), pre-emptive genotyping of a panel of clinically relevant PGx-markers, for which guidelines are available, will be implemented across healthcare institutions in seven European countries. The impact on patient outcomes and cost-effectiveness will be investigated. The program is unique in its multicenter, multigene, multidrug, multi-ethnic, and multihealthcare system approach.

irinotecan. The starting dose of biweekly irinotecan was 215 mg/m 2 for both genotype groups, whereas the dose of infusional fluorouracil was fixed. Pharmacokinetic data of irinotecan and metabolites were also obtained. ResultsThe dose of irinotecan was escalated to 370 mg/m 2 in patients with the *1/*28 genotype and to 420 mg/m 2 in those with the *1/*1 genotype. Dose-limiting toxicities (DLTs) were observed in two of four of *1/*28 patients at 370 mg/m 2 and in two of three of *1/*1 patients at 420 mg/m 2 . No DLTs were observed in 10 *1/*28 patients at 310 mg/m 2 and in 10 *1/*1 patients at 370 mg/m 2 ; hence these dose levels were the MTD for each genotype group. The most common grade 3 to 4 toxicities were neutropenia and diarrhea. The pharmacokinetics of irinotecan and SN-38 exhibit linear kinetics. ConclusionThe recommended dose of 180 mg/m 2 for irinotecan in FOLFIRI is considerably lower than the dose that can be tolerated when patients with the UGT1A1*28/*28 genotype are excluded. Prospective genotype-driven studies should test the efficacy of higher irinotecan doses in the FOLFIRI schedule.

ExoDOX is safer and more effective than free DOX. Importantly, the first spontaneous transformed syngeneic model of high-grade serous ovarian cancer was utilized for providing a new therapeutic opportunity.

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