In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 10 ( 2022-10-21), p. e0276497-
Abstract:
Skin rash is a well-known predictive marker of the response to cetuximab (Cmab) in metastatic colorectal cancer (mCRC). However, the mechanism of skin rash development is not well understood. Following exposure to EGFR-targeted therapies, changes in IL-8 levels have been reported. The aim of this study was to evaluate the association between skin rash and inflammatory cytokine levels, including IL-8. Between 2014 and 2017, we prospectively enrolled 38 mCRC patients who underwent chemotherapy with either Cmab or bevacizumab (Bmab) at two hospitals. We performed multiplex cytokine ELISA with 20 inflammatory cytokines including E-selectin, GM-CSF, IFN-alpha, IFN-γ, IL-1 alpha, IL-1 beta, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IP-10, MCP-1, MIP-1 alpha, MIP-1 beta, P-selectin, sICAM-1, and TNF-alpha at baseline before cycle 1, 24 h after cycle 1, before cycle 2 (= 14 d), and before cycle 3 (= 28 d). Cytokine levels were compared using ANOVA after log-transformation. IL-8 genotypes in 30 patients treated with Cmab were determined using the polymerase chain reaction restriction fragment length polymorphism technique. Depending on the RAS mutational status, 30 and eight patients were treated with Cmab and Bmab-based chemotherapy, respectively. Skin rash developed in 23 (76.6%) of the 30 patients treated with Cmab plus FOLFIRI, after cycle 1. Only the mean log-transformed serum IL-8 level in patients with skin toxicity was statistically lower (2.83 ± 0.15) than in patients who did not experience skin toxicity (3.65 ± 0.27) and received Bmab (3.10 ± 0.26) (ANOVA test, p value = 0.0341). In addition, IL-8 polymorphism did not affect IL-8 levels, skin toxicity, or tumor response in Cmab treated patients. This study suggests that the inflammatory cytokine levels might be affected by Cmab exposure and are associated with the development of skin rash in mCRC patients. Further studies are warranted to evaluate this interaction in Cmab treated patients.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0276497
DOI:
10.1371/journal.pone.0276497.g001
DOI:
10.1371/journal.pone.0276497.g002
DOI:
10.1371/journal.pone.0276497.g003
DOI:
10.1371/journal.pone.0276497.t001
DOI:
10.1371/journal.pone.0276497.t002
DOI:
10.1371/journal.pone.0276497.t003
DOI:
10.1371/journal.pone.0276497.t004
DOI:
10.1371/journal.pone.0276497.t005
DOI:
10.1371/journal.pone.0276497.t006
DOI:
10.1371/journal.pone.0276497.s001
DOI:
10.1371/journal.pone.0276497.s002
DOI:
10.1371/journal.pone.0276497.s003
DOI:
10.1371/journal.pone.0276497.s004
DOI:
10.1371/journal.pone.0276497.r001
DOI:
10.1371/journal.pone.0276497.r002
DOI:
10.1371/journal.pone.0276497.r003
DOI:
10.1371/journal.pone.0276497.r004
DOI:
10.1371/journal.pone.0276497.r005
DOI:
10.1371/journal.pone.0276497.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2267670-3
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