ArticleBritish journal of cancer2022
Integration of DNA sequencing with population pharmacokinetics to improve the prediction of irinotecan exposure in cancer patients.
Article in British journal of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
- Clinical perspective on management of key adverse events with sacituzumab govitecan.The oncologist · 2025Review
- Implementation of pre-emptive testing of a pharmacogenomic panel in clinical practice: Where do we stand?British journal of clinical pharmacology · 2025Review
- Association between SLCO1B1 genetic polymorphisms and bleeding risk in patients treated with edoxaban.Scientific reports · 2023Article
- Article
- Article
- Model-Based Prediction of Irinotecan-Induced Grade 4 Neutropenia in Advanced Cancer Patients: Influence of Demographic and Clinical Factors.Clinical pharmacology and therapeutics · 2022Article
- All You Need to Know AboutJCO oncology practice · 2022Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIrinotecan (CPT-11) is an anticancer agent widely used to treat adult solid tumours. Large interindividual variability in the clearance of irinotecan and SN-38, its active and toxic metabolite, results in highly unpredictable toxicity.
methodsIn 217 cancer patients treated with intravenous irinotecan single agent or in combination, germline DNA was used to interrogate the variation in 84 genes by next-generation sequencing. A stepwise analytical framework including a population pharmacokinetic model with SNP- and gene-based testing was used to identify demographic/clinical/genetic factors that influence the clearance of irinotecan and SN-38.
resultsIrinotecan clearance was influenced by rs4149057 in SLCO1B1, body surface area, and co-administration of 5-fluorouracil/leucovorin/bevacizumab. SN-38 clearance was influenced by rs887829 in UGT1A1, pre-treatment total bilirubin, and EGFR rare variant burden. Within each UGT1A1 genotype group, elevated pre-treatment total bilirubin and/or presence of at least one rare variant in EGFR resulted in significantly lower SN-38 clearance. The model reduced the interindividual variability in irinotecan clearance from 38 to 34% and SN-38 clearance from 49 to 32%.
conclusionsThis new model significantly reduced the interindividual variability in the clearance of irinotecan and SN-38. New genetic factors of variability in clearance have been identified.
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