Highlights
- •Severity of skin rash was associated with treatment outcome in terms of progression free survival (PFS) and overall survival (OS) in cancer patients treated with tyrosine kinase inhibitors.
- •Drug-metabolising activity assessed by the erlotinib/O-desmethyl-erlotinib metabolic ratio was observed to be correlated with the severity of skin rash in that way that high metabolic activity lowers the occurrence of skin rash.
- •The erlotinib/O-desmethyl-erlotinib metabolic ratio was also highly associated with PFS and OS in cancer patients.
- •The individual metabolic activity of erlotinib determined in serum may be helpful for therapeutic monitoring in erlotinib treatment and decisions on individual dosing to rash in rash-negative cancer patients.
Abstract
Aim
The aim of this study was to investigate if biomarkers of individual drug metabolism,
respectively, the erlotinib/O-desmethyl-erlotinib metabolic ratio, may be a predictive
factor for the severity of erlotinib-mediated skin rash in epidermal growth factor
receptor (EGFR) inhibitor-treated patients suffering from epithelial cancers. This
is especially important since it is known that the severity of skin rash has a prognostic
value on outcome and survival in cancer patients experiencing skin rash under treatment
with EGFR inhibitors.
Methods
From 2008 to 2014, 96 patients, n = 63 suffering from histologically confirmed non-small-cell
lung cancer and n = 33 from pancreatic adenocarcinoma were observed for the occurrence
and severity of skin rash after the onset of treatment with erlotinib. The primary
end-points (occurrence and severity of skin rash, progression-free survival [PFS]
and overall survival [OS]) were analysed with regard to erlotinib and its metabolite
O-desmethyl-erlotinib trough serum concentrations measured at 4 weeks after onset
of therapy by the use of correlation, multiple regression and survival analysis.
Results
Occurrence of skin rash was associated with PFS (p = 0.0042) and OS (p = 0.017) in
the overall cohort of erlotinib-treated cancer patients. Drug-metabolising activity
assessed by the erlotinib/O-desmethyl-erlotinib metabolic ratio was correlated with
severity of skin rash (p = 0.023) and as well highly associated with both PFS (p = 2.1 × 10−4) and OS (p = 5.8 × 10−5).
Conclusion
The erlotinib/O-desmethyl-erlotinib metabolic ratio reflecting the individual metabolic
activity of erlotinib correlated with the severity of skin rash and outcome in patients
treated with EGFR tyrosine kinase inhibitors. The metabolic ratio determined in serum
may be used for therapeutic monitoring in erlotinib treatment and decisions on individual
dosing to rash in rash-negative patients.
Keywords
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Article info
Publication history
Published online: January 25, 2016
Accepted:
November 22,
2015
Received:
November 19,
2015
Identification
Copyright
© 2015 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
