ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2010
Genotype-driven phase I study of irinotecan administered in combination with fluorouracil/leucovorin in patients with metastatic colorectal cancer.
Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 2 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
79 citing papers in PubMed, 2 syntheses or guidelines pooled it, 167 citations in OpenAlex.
- Pooled it
- The effect of the UGT1A1*28 allele on survival after irinotecan-based chemotherapy: a collaborative meta-analysis.The pharmacogenomics journal · 2014Pooled it
- A phase II trial of UGT1A1 genotype-guided FOLFIRI plus bevacizumab as first-line therapy for advanced, unresectable colorectal cancer.The oncologist · 2024Trial
- A phase-II study based on dose adjustment according to UGT1A1 polymorphism: is irinotecan underdosed in first-line FOLFIRI regimen for mCRC?Cancer chemotherapy and pharmacology · 2024Trial
- 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
- Pharmacogenetic clinical randomised phase II trial to evaluate the efficacy and safety of FOLFIRI with high-dose irinotecan (HD-FOLFIRI) in metastatic colorectal cancer patients according to their UGT1A 1 genotype.British journal of cancer · 2019Trial
- Pharmacogenetic Analysis of the UK MRC (Medical Research Council) MAGIC Trial: Association of Polymorphisms with Toxicity and Survival in Patients Treated with Perioperative Epirubicin, Cisplatin, and 5-fluorouracil (ECF) Chemotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- Trial
- Observational
- Dose-Limiting Toxicities and the Maximum Tolerated Dose of Irinotecan Based onPharmaceutics · 2025Review
- Generation of anti-SN38 antibody for loading efficacy and therapeutic monitoring of SN38-containing therapeutics.Heliyon · 2024Article
- Assessing the Occurrence and Influence of Cancer Chemotherapy-Related Pharmacogenetic Alleles in the Chilean Population.Pharmaceutics · 2024Article
- Molecular panorama of therapy resistance in prostate cancer: a pre-clinical and bioinformatics analysis for clinical translation.Cancer metastasis reviews · 2024Review
- Irinotecan-Induced Toxicity: A Pharmacogenetic Study Beyond UGT1A1.Clinical pharmacokinetics · 2023Article
- Comprehensive network analysis of dysregulated genes revealed MNX1-AS1/hsa-miR-4697-3p/HOXB13 axis in ovarian cancer chemotherapy response.Cancer science · 2022Article
- Model-Based Prediction of Irinotecan-Induced Grade 4 Neutropenia in Advanced Cancer Patients: Influence of Demographic and Clinical Factors.Clinical pharmacology and therapeutics · 2022Article
- Modern developments in germline pharmacogenomics for oncology prescribing.CA: a cancer journal for clinicians · 2022Review
- Irinotecan dose reduction in metastatic colorectal cancer patients with homozygousThe Journal of international medical research · 2022Article
- Comparison ofOncology research · 2022Observational
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
PURPOSE We aimed to identify the maximum-tolerated dose (MTD) of irinotecan in patients with cancer with UGT1A1*1/*1 and *1/*28 genotypes. We hypothesize that the patients without the *28/*28 genotype tolerate higher doses of irinotecan. PATIENTS AND METHODS Patients undergoing first-line treatment for metastatic colorectal cancer (CRC) eligible for treatment with irinotecan plus infusional fluorouracil/leucovorin (FOLFIRI) were screened for the UGT1A1*28/*28 genotype and excluded from the study. Fifty-nine white patients with either the *1/*1 or the *1/*28 genotype were eligible for dose escalation of 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. Results The 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. CONCLUSION The 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.
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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.