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Correlation of plasma erlotinib trough concentration with skin rash in Chinese NSCLC patients harboring exon 19 deletion mutation

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Abstract

Purpose

Erlotinib is an essential drug for non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) activating mutations. The relationship between the pharmacokinetics and skin rash and diarrhea of erlotinib in Chinese patients with EGFR mutated NSCLC is unknown. In this study, we evaluated the variability in erlotinib trough concentration and its relationship with the severity of skin rash and diarrhea in patients with two common types of EGFR mutations: a deletion in exon 19 and point mutations in exon 21 L858R.

Patients and methods

EGFR mutation-positive Chinese patients (n = 52) treated with erlotinib were included in our study; the steady-state trough concentrations were assessed; and the occurrence and severity of skin rash and diarrhea after the onset of treatment with erlotinib were recorded. The patients were divided into two groups by mutation type (exon 19 deletions or exon 21 L858R point mutations). Occurrence and severity of skin rash and diarrhea was analyzed in both groups.

Results

The overall mean (± SD) steady-state trough concentration for erlotinib was 1380 ± 663 ng/mL, and there was no significant difference of erlotinib concentrations between the two mutation groups. Occurrence and severity of skin rash was significantly associated with trough concentration in patients with exon 19 deletions but not exon 21 L858R point mutations. Significant association of erlotinib concentrations with diarrhea was found neither in the exon 19 deletions group nor in the exon 21 L858R point mutation group.

Conclusions

The occurrence and severity of skin rash correlated with increase in erlotinib trough concentrations only in Chinese patients with exon 19 deletion; the erlotinib trough concentrations were not associated with diarrhea.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant number 81603206), Hunan Provincial Pharmaceutical Association Fund (Grant number hn2017005), and Health and Family Planning Commission Foundation of Hunan Province (Grant number B20180252).

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Authors and Affiliations

  1. Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha, 410011, China

    Dehua Liao & Daxiong Xiang

  2. Department of Pharmacy, Hunan Cancer Hospital, Changsha, 410011, China

    Dehua Liao, Dunwu Yao, Ni Liu & Lizhi Cao

  3. Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital, Changsha, 410011, China

    Nong Yang, Yongchang Zhang, Wenjuan Jiang & Chunhua Zhou

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  1. Dehua Liao
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  2. Dunwu Yao
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  3. Ni Liu
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  5. Daxiong Xiang
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Contributions

DL, NY, and DX designed the study and wrote the protocol. DL, NL, YZ, WJ, and CZ performed the experiments, analyzed the data, and revised the manuscript. DY and LC contributed to the reagents and materials. DL drafted the manuscript. DL and NY revised the manuscript content. All the authors read and approved the final manuscript.

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Correspondence to Daxiong Xiang or Nong Yang.

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The authors declare no conflict of interest.

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Liao, D., Yao, D., Liu, N. et al. Correlation of plasma erlotinib trough concentration with skin rash in Chinese NSCLC patients harboring exon 19 deletion mutation. Cancer Chemother Pharmacol 82, 551–559 (2018). https://doi.org/10.1007/s00280-018-3642-4

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