We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Pre-treatment amino acids and risk of paclitaxel-induced peripheral neuropathy in SWOG S0221.
- Authors
Chen, Ciao-Sin; Zirpoli, Gary; Budd, G. Thomas; Barlow, William E.; Pusztai, Lajos; Hortobagyi, Gabriel N.; Albain, Kathy S.; Godwin, Andrew K.; Thompson, Alastair; Henry, N. Lynn; Ambrosone, Christine B.; Stringer, Kathleen A.; Hertz, Daniel L.
- Abstract
Background: Chemotherapy-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. Methods: Pre-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. Results: In 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. Conclusions: This 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.
- Subjects
AMINO acids; BODY mass index; PHENYLALANINE; PERIPHERAL neuropathy; BONFERRONI correction; PACLITAXEL
- Publication
Cancer Chemotherapy & Pharmacology, 2024, Vol 94, Issue 2, p311
- ISSN
0344-5704
- Publication type
Article
- DOI
10.1007/s00280-024-04680-6