ArticleInvestigational new drugs2013
UGT1A1 genotype-guided phase I study of irinotecan, oxaliplatin, and capecitabine.
Article in Investigational new drugs, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00433550 (A Phase II Trial of Pharmacogenetic-Based Dosing of Irinotecan, Oxaliplatin, and Capecitabine as First-Line Therapy for Advanced Small Bowel Adenocarcinoma), which is not on this map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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.
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.
A Phase II Trial of Pharmacogenetic-Based Dosing of Irinotecan, Oxaliplatin, and Capecitabine as First-Line Therapy for Advanced Small Bowel Adenocarcinoma
Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Dutch pharmacogenetics working group (DPWG) guideline for the gene-drug interaction between UGT1A1 and irinotecan.European journal of human genetics : EJHG · 2023Guideline
- Phase II Trial of Alisertib in Combination with Irinotecan and Temozolomide for Patients with Relapsed or Refractory Neuroblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Trial
- Trial
- Real-world analysis of genotype-guided treatment for carriers of actionable DPYD and UGT1A1 variants.The pharmacogenomics journal · 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
- Modern developments in germline pharmacogenomics for oncology prescribing.CA: a cancer journal for clinicians · 2022Review
- FOLFIRINOXWorld journal of gastrointestinal oncology · 2020Article
- Dosage Adjustment of Irinotecan in Patients with UGT1A1 Polymorphisms: A Review of Current Literature.Innovations in pharmacy · 2020Review
- Opportunities and challenges of implementing Pharmacogenomics in cancer drug development.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Different schedules of irinotecan administration: A meta-analysis.Molecular and clinical oncology · 2016Article
- Phase I Study of the Aurora A Kinase Inhibitor Alisertib in Combination With Irinotecan and Temozolomide for Patients With Relapsed or Refractory Neuroblastoma: A NANT (New Approaches to Neuroblastoma Therapy) Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2016Article
- UGT genotyping in belinostat dosing.Pharmacological research · 2016Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
purposeWe performed a UGT1A1 genotype-guided study to determine the maximum tolerated dose (MTD) and evaluate the toxicities and pharmacokinetics of the combination of capecitabine (CAP), oxaliplatin (OX), and irinotecan (IRIN). EXPERIMENTAL
designPatients were screened for UGT1A1 *28 genotype prior to treatment. The starting dose (mg/m(2)) was IRIN (150), OX (85) and CAP (400), days 2-15. Doses were escalated or de-escalated within each genotype group (*28/*28, *1/*28 and *1/*1). IRIN pharmacokinetics was performed at the MTD.
results50 patients were evaluable for toxicity [11 (*28/*28); 18 (*1/*28); 21 (*1/*1)]. UGT1A1 *28/*28 patients experienced hematologic dose limiting toxicity (DLT), requiring dose-de-escalation. The UGT1A1 *28/*28 recommended phase 2 dose (RP2D) was IRIN (75), OX (85), and CAP (400). In contrast, both UGT1A1 *1/*28 and *1/*1 tolerated higher doses of IRIN and non-hematologic toxicity was dose limiting for UGT1A1 *1/*1. The RP2D was IRIN (150), OX (85), and CAP (400) for UGT1A1*1/*28 and IRIN (150), OX (100), and CAP (1600) for UGT1A1 *1/*1. UGT1A1 *1/*28 and *1/*1 patients treated with IRIN (150) had similar AUCs for the active irinotecan metabolite, SN38 (366 +/- 278 and 350 +/- 159 ng/ml*hr, respectively). UGT1A1 *28/*28 patients (n = 3) treated with a lower IRIN dose (100) had non-significantly higher mean SN38 exposures (604 +/- 289 ng/ml*hr, p = 0.14). Antitumor activity was observed in all genotype groups.
conclusionsUGT1A1 genotype affects the dose and pharmacokinetics of the CAPIRINOX regimen and UGT1A1 genotype-guided dosing of CAPIRINOX is ongoing in a phase II study of small bowel cancer (NCT00433550).
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