ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2014
Dose-finding and pharmacokinetic study to optimize the dosing of irinotecan according to the UGT1A1 genotype of patients with cancer.
Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 3 of them syntheses that pooled it.
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The trial behind it
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
83 citing papers in PubMed, 3 syntheses or guidelines pooled it, 138 citations in OpenAlex.
- Pre-Therapeutic UGT1A1 Genotyping in Breast Cancer Patients Receiving Sacituzumab Govitecan to Improve Safety: A Meta-Analysis and Recommendation.Clinical and translational science · 2026Pooled it
- Pooled it
- Irinotecan-induced toxicity pharmacogenetics: an umbrella review of systematic reviews and meta-analyses.The pharmacogenomics journal · 2017Pooled it
- Neoadjuvant chemoradiotherapy with capecitabine and irinotecan guided by UGT1A1 status in patients with locally advanced rectal cancer: 5-year update of the CinClare trial.Cancer communications (London, England) · 2025Trial
- Longitudinal patient-reported outcomes on genotype-guided irinotecan dosing: feasibility and clinical relevance.The oncologist · 2024Trial
- A phase II trial of UGT1A1 genotype-guided FOLFIRI plus bevacizumab as first-line therapy for advanced, unresectable colorectal cancer.The oncologist · 2024Trial
- Serum metabolic traits reveal therapeutic toxicities and responses of neoadjuvant chemoradiotherapy in patients with rectal cancer.Nature communications · 2022Trial
- Multicenter, Randomized, Phase III Trial of Neoadjuvant Chemoradiation With Capecitabine and Irinotecan Guided byJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020Trial
- Clinical Assessment of 5-Fluorouracil/Leucovorin, Nab-Paclitaxel, and Irinotecan (FOLFIRABRAX) in Untreated Patients with Gastrointestinal Cancer UsingClinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- Trial
- Pharmacokinetics of Irinotecan, Oxaliplatin and 5-Fluorouracil During Hepatic Artery Chronomodulated Infusion: A Translational European OPTILIV Study.Clinical pharmacokinetics · 2017Trial
- Effect of Single Nucleotide Polymorphisms in the Xenobiotic-sensing Receptors NR1I2 and NR1I3 on the Pharmacokinetics and Toxicity of Irinotecan in Colorectal Cancer Patients.Clinical pharmacokinetics · 2016Trial
- Phenotyping of UGT1A1 Activity Using Raltegravir Predicts Pharmacokinetics and Toxicity of Irinotecan in FOLFIRI.PloS one · 2016Trial
- Phase I design for partially ordered groups with late-onset toxicity.Clinical trials (London, England) · 2026Article
- Comparative efficacy and safety of first-line treatments for RAS wild-type metastatic colorectal cancer: A systematic review and network meta-analysis.Molecular and clinical oncology · 2026Article
- Development of a simplified population pharmacokinetic-pharmacodynamic framework for exposure-informed risk stratification of neutropenia during amrubicin treatment.Cancer chemotherapy and pharmacology · 2026Article
- Survival of patients with colorectal or pancreatic cancer who receivedThe Lancet regional health. Europe · 2026Article
- Dose-Limiting Toxicities and the Maximum Tolerated Dose of Irinotecan Based onPharmaceutics · 2025Review
- Tall cell carcinoma with reversed polarity of breast cancer: a rare case report and review of the literature.Frontiers in oncology · 2025Article
- The role of UGT1A1 polymorphism in the management of colorectal cancer.Oncology reviews · 2025Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
purposeThe risk of severe neutropenia from treatment with irinotecan is related in part to UGT1A1*28, a variant that reduces the elimination of SN-38, the active metabolite of irinotecan. We aimed to identify the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of irinotecan in patients with advanced solid tumors stratified by the *1/*1, *1/*28, and *28/*28 genotypes. PATIENTS AND
methodsSixty-eight patients received an intravenous flat dose of irinotecan every 3 weeks. Forty-six percent of the patients had the *1/*1 genotype, 41% had the *1/*28 genotype, and 13% had the *28/*28 genotype. The starting dose of irinotecan was 700 mg in patients with the *1/*1 and *1/*28 genotypes and 500 mg in patients with the *28/*28 genotype. Pharmacokinetic evaluation was performed at cycle 1.
resultsIn patients with the *1/*1 genotype, the MTD was 850 mg (four DLTs per 16 patients), and 1,000 mg was not tolerated (two DLTs per six patients). In patients with the *1/*28 genotype, the MTD was 700 mg (five DLTs per 22 patients), and 850 mg was not tolerated (four DLTs per six patients). In patients with the *28/*28 genotype, the MTD was 400 mg (one DLT per six patients), and 500 mg was not tolerated (three DLTs per three patients). The DLTs were mainly myelosuppression and diarrhea. Irinotecan clearance followed linear kinetics. At the MTD for each genotype, dosing by genotype resulted in similar SN-38 areas under the curve (AUCs; r(2) = 0.0003; P = .97), but the irinotecan AUC was correlated with the actual dose (r(2) = 0.39; P < .001). Four of 48 patients with disease known to be responsive to irinotecan achieved partial response.
conclusionThe UGT1A1*28 genotype can be used to individualize dosing of irinotecan. Additional studies should evaluate the effect of genotype-guided dosing on efficacy in patients receiving irinotecan.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.