Evidence map›Paper›PMID 36527823›Full record

ArticleESMO open2023

The association between UGT1A1 polymorphisms and treatment toxicities of liposomal irinotecan.

Y-Y Su, N-J Chiang, J S Chang, Y-W Wang, B-N Shen, Y-J Li, D-Y Hwang, Y-S Shan, L-T Chen

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In one paragraph

Article in ESMO open, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  3. Clinical Implications ofPharmaceutics · 2026
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4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

9 authors.

Y-Y SuNational Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan; Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
N-J ChiangNational Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan; Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
J S ChangNational Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
Y-W WangPharmaEngine, Inc., Taipei, Taiwan.
B-N ShenPharmaEngine, Inc., Taipei, Taiwan.
Y-J LiNational Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
D-Y HwangNational Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
Y-S ShanInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address: ysshan@mail.ncku.edu.tw.
L-T ChenNational Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan; Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Internal Medicine, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: leochen@nhri.org.tw.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundInitial dose adjustment is recommended for patients with known UGT1A1∗28 homozygosity for both conventional irinotecan and liposomal irinotecan (nal-IRI). A recent population pharmacokinetic (PK) study showed that Asian patients had a lower prevalence of UGT1A1∗28 homozygosity but a significantly higher maximum blood concentration of SN-38 (SN-38 Cmax) and a higher incidence of grade ≥3 neutropenia after nal-IRI administration than Caucasian patients. The current study investigated the association of UGT1A1 polymorphisms, including the Asian prevalent UGT1A1∗6, PK and toxicities of nal-IRI-based therapy in the Asian population. PATIENTS AND

methodsA total of 162 patients with nal-IRI-based therapy and available UGT1A1∗6 and UGT1A1∗28 genotyping were included, with 82 Asian patients from six previous phase I or II studies of nal-IRI (cohort 1) and another 80 patients with nal-IRI + 5-fluorouracil/leucovorin every 2 weeks as real-world practice in a single institute in Taiwan (cohort 2).

resultsThe frequency of UGT1A1∗6 or UGT1A1∗28 homozygosity/compound heterozygosity was 9.3%, with UGT1A1∗6/∗6 in 2.5%, UGT1A1∗28/∗28 in 1.9% and UGT1A1∗6/∗28 in 4.9%. Among the 53 patients in cohort 1 with available PK data, all 7 patients with homozygosity/compound heterozygosity harbored UGT1A1∗6 and had a significantly higher level of median dose-normalized area under the concentration-time curve (AUC) and Cmax of SN-38 than those with single heterozygosity/wild type. Of the entire study population, the incidence of grade ≥3 neutropenia and diarrhea was significantly higher in patients with homozygosity/compound heterozygosity than in those with single heterozygosity/wild type, 73.3% versus 38.1% (P = 0.012, Fisher's exact test) and 33.3% versus 9.5% (P = 0.018, Fisher's exact test), respectively.

conclusionThe results suggest that the recommendation of a lower starting dose of nal-IRI for patients with UGT1A1∗28 homozygosity should be extended to include patients with UGT1A1∗6 homozygosity/compound heterozygosity.

Indexed as

CamptothecinNeutropeniaGenotypeHumansIrinotecanPolymorphism, GeneticCamptothecinIrinotecanAsiandiarrheanal-IRIneutropeniaUGT1A1∗6

Identifiers

PMID36527823
PMCPMC10024091

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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.