Evidence map›Paper›PMID 38814343›Full record

Trial reportCancer chemotherapy and pharmacology2024

Pre-treatment amino acids and risk of paclitaxel-induced peripheral neuropathy in SWOG S0221.

Ciao-Sin Chen, Gary Zirpoli, G Thomas Budd, William E Barlow, Lajos Pusztai, Gabriel N Hortobagyi, Kathy S Albain, Andrew K Godwin, Alastair Thompson, N Lynn Henry and 3 more

Registry-linked trialAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in Cancer chemotherapy and pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00070564 (Phase III Trial of Continuous Schedule AC + G vs. Q 2 Week Schedule AC, Followed by Paclitaxel Given Either Every 2 Weeks or Weekly for 12 Weeks as Post-Operative Adjuvant Therapy in Node-Positive or High-Risk Node-Negative Breast Cancer), which is not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–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

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.

NCT00070564 phase3active not recruitingnot on this map

Phase III Trial of Continuous Schedule AC + G vs. Q 2 Week Schedule AC, Followed by Paclitaxel Given Either Every 2 Weeks or Weekly for 12 Weeks as Post-Operative Adjuvant Therapy in Node-Positive or High-Risk Node-Negative Breast Cancer

TypeinterventionalSponsorSWOG Cancer Research NetworkRan2003 to 2027Enrolled3,294ConditionsBreast CancerArmspegfilgrastim, AC regimen, cyclophosphamide, doxorubicin hydrochloride, paclitaxel
3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Ciao-Sin ChenDepartment of Clinical Pharmacy, University of Michigan College of Pharmacy, 428 Church St. 1100 North University Building Room 2560C, Ann Arbor, MI, 48109-1065, USA.ORCID 0000-0002-5917-0958
Gary ZirpoliSlone Epidemiology Center, Boston University, Boston, MA, USA.ORCID 0000-0003-1417-5349
G Thomas BuddDepartment of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, OH, USA.
William E BarlowCancer Research and Biostatistics, Seattle, WA, USA.ORCID 0000-0003-4651-2282
Lajos PusztaiYale School of Medicine, New Haven, CT, USA.ORCID 0000-0001-9632-6686
Gabriel N HortobagyiBreast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0002-4873-4412
Kathy S AlbainLoyola University Chicago Stritch School of Medicine, Maywood, IL, USA.ORCID 0000-0002-2899-2473
Andrew K GodwinDepartment of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.ORCID 0000-0002-3987-9580
Alastair ThompsonBaylor College of Medicine, Houston, TX, USA.
N Lynn HenryDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.ORCID 0000-0002-4771-5930
Christine B AmbrosoneDepartment of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.ORCID 0000-0003-1717-9943
Kathleen A StringerDepartment of Clinical Pharmacy, University of Michigan College of Pharmacy, 428 Church St. 1100 North University Building Room 2560C, Ann Arbor, MI, 48109-1065, USA.ORCID 0000-0003-0238-7774
Daniel L HertzDepartment of Clinical Pharmacy, University of Michigan College of Pharmacy, 428 Church St. 1100 North University Building Room 2560C, Ann Arbor, MI, 48109-1065, USA. dlhertz@med.umich.edu.ORCID 0000-0003-0501-1035

Funding

SWOG Network Group Operations Center of the NCTNU10CA180888 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI PRIMO N. LARA · 2014 to 2026
$152.1M
SWOG Statistics & Data Management Center complex - extension supplement for GY06U10CA180819 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI MEGAN OTHUS · 2014 to 2026
$115.2M
Translational Metabolomics in Critical CareR35GM136312 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KATHLEEN A STRINGER · 2020 to 2026
$2.8M
(PQ12) Peroxisome proliferator-activated receptor alpha agonists as potential treatment for chemotherapy-induced peripheral neuropathyR01CA219637 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI DAMAJ, M. IMAD, GEWIRTZ, DAVID A. · 2018 to 2021
$1.2M
American Cancer Society N030566-497333National Cancer Institute, United States R01CA219637National Cancer Institute, United States U10CA180819National Cancer Institute, United States U10CA180888NCI NIH HHS R01 CA219637NCI NIH HHS U10 CA180819NCI NIH HHS U10 CA180888NIGMS NIH HHS R35 GM136312
6 · The paper itself

Abstract

backgroundChemotherapy-induced peripheral neuropathy (CIPN) is a treatment-limiting and debilitating neurotoxicity of many commonly used anti-cancer agents, including paclitaxel. The objective of this study was to confirm the previously found inverse association between pre-treatment blood concentrations of histidine and CIPN occurrence and examine relationships of other amino acids with CIPN severity.

methodsPre-treatment serum concentrations of 20 amino acids were measured in the SWOG S0221 (NCT00070564) trial of patients with early-stage breast cancer receiving paclitaxel. The associations between amino acids and CIPN severity were tested in regression analysis adjusted for paclitaxel schedule, age, self-reported race, and body mass index with Bonferroni correction. The network of metabolic pathways of amino acids was analyzed using over-representation analysis. The partial correlation network of amino acids was evaluated using a debiased sparse partial correlation algorithm.

resultsIn the primary analysis, histidine concentration was not associated with CIPN occurrence (odds ratio (OR) = 0.97 [0.83, 1.13], p = 0.72). In secondary analyses, higher concentrations of four amino acids, glutamate (β = 0.58 [0.23, 0.93], p = 0.001), phenylalanine (β = 0.54 [0.19, 0.89], p = 0.002), tyrosine (β = 0.57 [0.23, 0.91], p = 0.001), and valine (β = 0.58 [0.24, 0.92], p = 0.001) were associated with more severe CIPN, but none of these associations retained significance after adjustment. In the over-representation analysis, no amino acid metabolic pathways were significantly enriched (all FDR > 0.05). In the network of enriched pathways, glutamate metabolism had the highest centrality.

conclusionsThis analysis showed that pre-treatment serum amino acid concentrations are not strongly predictive of CIPN severity. Prospectively designed studies that assess non-amino acid metabolomics predictors are encouraged.

Indexed as

Amino AcidsBreast NeoplasmsPaclitaxelPeripheral Nervous System DiseasesAdultAgedAntineoplastic Agents, PhytogenicFemaleHumansMiddle AgedSeverity of Illness IndexAmino AcidsAntineoplastic Agents, PhytogenicPaclitaxelAmino acidChemotherapy-induced peripheral neuropathyHistidinePaclitaxelPharmacometabolomicsPredictive biomarkersRisk factorsSymptom science

Identifiers

PMID38814343
PMCPMC11878155

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Registered trials

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.