Zinc deficiency associated with cutaneous toxicities induced by epidermal growth factor receptor tyrosine kinase inhibitor therapy in patients with lung adenocarcinoma

Chun Wei Lu; Jong Hwei Su Pang; Yu Shien Ko; Chih Jung Chang; Chuang Wei Wang; Wei Ti Chen; Chun Bing Chen; Rosaline Chung yee Hui; Shuen Iu Hung; Lai Ying Lu; Kun Lin Lu; Chih Liang Wang; Chiao En Wu; Ping Chih Hsu; Yueh Fu Fang; Shih Hong Li; How Wen Ko; Li Chuan Tseng; Feng Ya Shih; Mei Jun Chen; Wen Hung Chung

doi:10.1111/jdv.18703

Zinc deficiency associated with cutaneous toxicities induced by epidermal growth factor receptor tyrosine kinase inhibitor therapy in patients with lung adenocarcinoma

Chun Wei Lu, Jong Hwei Su Pang, Yu Shien Ko, Chih Jung Chang, Chuang Wei Wang, Wei Ti Chen, Chun Bing Chen, Rosaline Chung yee Hui, Shuen Iu Hung, Lai Ying Lu, Kun Lin Lu, Chih Liang Wang, Chiao En Wu, Ping Chih Hsu, Yueh Fu Fang, Shih Hong Li, How Wen Ko, Li Chuan Tseng, Feng Ya Shih, Mei Jun ChenWen Hung Chung^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

9 Scopus citations

Abstract

PURPOSE: Cutaneous toxicities are common adverse effects following epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy. Zinc deficiency causes diverse diseases, including skin toxicities. Therefore, this study aimed to investigate the role of zinc deficiency in patients with EGFR-TKI-induced skin toxicities.

EXPERIMENTAL DESIGN: This retrospective study enrolled 269 patients with diverse skin disorders who visited our hospital between January 2016 and December 2017. The skin toxicity severities and plasma zinc levels of 101 EGFR-TKI-treated cancer patients were analysed and compared with those of 43 non-EGFR-TKI-treated cancer patients and 125 patients without cancer but presenting cutaneous manifestations. Additionally, the role of zinc in erlotinib-induced skin eruptions was established in a 14-day-murine model. Clinical features were further evaluated following systemic zinc supplementation in EGFR-TKI-treated cancer patients.

RESULTS: EGFR-TKI-treated patients demonstrated severe cutaneous manifestations and a significant decrease in plasma zinc levels than those of the control groups. The serum zinc level and Common Terminology Criteria for Adverse Events (CTCAE) 5.0 grading of EGFR-TKI-induced skin toxicities showed a significant negative correlation (r = -0.29; p < 0.0001). Moreover, erlotinib treatment decreased the plasma zinc levels and induced periorificial dermatitis in rats confirming zinc deficiency following EGFR-TKI treatment. Zinc supplementation to the EGFR-TKI-treated cancer patients showed a significant decrease in the CTCEA grading (p < 0.0005 for mucositis and p < 0.0.0001 for all other cases) after 8 weeks.

CONCLUSIONS: Skin impairment following EGFR-TKI therapy could be ameliorated through zinc supplementation. Thus, zinc supplementation should be considered for cancer patients undergoing EGFR-TKI therapy.

Original language	English
Pages (from-to)	328-339
Number of pages	12
Journal	Journal of the European Academy of Dermatology and Venereology
Volume	37
Issue number	2
DOIs	https://doi.org/10.1111/jdv.18703
State	Published - 02 2023

Bibliographical note

Keywords

Animals
Mice
Rats
Adenocarcinoma of Lung/drug therapy
ErbB Receptors
Erlotinib Hydrochloride/adverse effects
Exanthema/chemically induced
Lung Neoplasms/drug therapy
Mutation
Protein Kinase Inhibitors/adverse effects
Retrospective Studies
Tyrosine Kinase Inhibitors/adverse effects
Zinc/metabolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/jdv.18703

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Lu, C. W., Pang, J. H. S., Ko, Y. S., Chang, C. J., Wang, C. W., Chen, W. T., Chen, C. B., Hui, R. C. Y., Hung, S. I., Lu, L. Y., Lu, K. L., Wang, C. L., Wu, C. E., Hsu, P. C., Fang, Y. F., Li, S. H., Ko, H. W., Tseng, L. C., Shih, F. Y., ... Chung, W. H. (2023). Zinc deficiency associated with cutaneous toxicities induced by epidermal growth factor receptor tyrosine kinase inhibitor therapy in patients with lung adenocarcinoma. Journal of the European Academy of Dermatology and Venereology, 37(2), 328-339. https://doi.org/10.1111/jdv.18703

@article{a14db9f442914502b8a770c5c881198d,

title = "Zinc deficiency associated with cutaneous toxicities induced by epidermal growth factor receptor tyrosine kinase inhibitor therapy in patients with lung adenocarcinoma",

abstract = "PURPOSE: Cutaneous toxicities are common adverse effects following epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy. Zinc deficiency causes diverse diseases, including skin toxicities. Therefore, this study aimed to investigate the role of zinc deficiency in patients with EGFR-TKI-induced skin toxicities.EXPERIMENTAL DESIGN: This retrospective study enrolled 269 patients with diverse skin disorders who visited our hospital between January 2016 and December 2017. The skin toxicity severities and plasma zinc levels of 101 EGFR-TKI-treated cancer patients were analysed and compared with those of 43 non-EGFR-TKI-treated cancer patients and 125 patients without cancer but presenting cutaneous manifestations. Additionally, the role of zinc in erlotinib-induced skin eruptions was established in a 14-day-murine model. Clinical features were further evaluated following systemic zinc supplementation in EGFR-TKI-treated cancer patients.RESULTS: EGFR-TKI-treated patients demonstrated severe cutaneous manifestations and a significant decrease in plasma zinc levels than those of the control groups. The serum zinc level and Common Terminology Criteria for Adverse Events (CTCAE) 5.0 grading of EGFR-TKI-induced skin toxicities showed a significant negative correlation (r = -0.29; p < 0.0001). Moreover, erlotinib treatment decreased the plasma zinc levels and induced periorificial dermatitis in rats confirming zinc deficiency following EGFR-TKI treatment. Zinc supplementation to the EGFR-TKI-treated cancer patients showed a significant decrease in the CTCEA grading (p < 0.0005 for mucositis and p < 0.0.0001 for all other cases) after 8 weeks.CONCLUSIONS: Skin impairment following EGFR-TKI therapy could be ameliorated through zinc supplementation. Thus, zinc supplementation should be considered for cancer patients undergoing EGFR-TKI therapy.",

keywords = "Animals, Mice, Rats, Adenocarcinoma of Lung/drug therapy, ErbB Receptors, Erlotinib Hydrochloride/adverse effects, Exanthema/chemically induced, Lung Neoplasms/drug therapy, Mutation, Protein Kinase Inhibitors/adverse effects, Retrospective Studies, Tyrosine Kinase Inhibitors/adverse effects, Zinc/metabolism",

author = "Lu, {Chun Wei} and Pang, {Jong Hwei Su} and Ko, {Yu Shien} and Chang, {Chih Jung} and Wang, {Chuang Wei} and Chen, {Wei Ti} and Chen, {Chun Bing} and Hui, {Rosaline Chung yee} and Hung, {Shuen Iu} and Lu, {Lai Ying} and Lu, {Kun Lin} and Wang, {Chih Liang} and Wu, {Chiao En} and Hsu, {Ping Chih} and Fang, {Yueh Fu} and Li, {Shih Hong} and Ko, {How Wen} and Tseng, {Li Chuan} and Shih, {Feng Ya} and Chen, {Mei Jun} and Chung, {Wen Hung}",

note = "{\textcopyright} 2022 European Academy of Dermatology and Venereology.",

year = "2023",

month = feb,

doi = "10.1111/jdv.18703",

language = "英语",

volume = "37",

pages = "328--339",

journal = "Journal of the European Academy of Dermatology and Venereology",

issn = "0926-9959",

publisher = "John Wiley and Sons Inc",

number = "2",

}

Lu, CW, Pang, JHS, Ko, YS, Chang, CJ, Wang, CW, Chen, WT, Chen, CB, Hui, RCY, Hung, SI, Lu, LY, Lu, KL, Wang, CL, Wu, CE , Hsu, PC, Fang, YF, Li, SH, Ko, HW, Tseng, LC, Shih, FY, Chen, MJ & Chung, WH 2023, 'Zinc deficiency associated with cutaneous toxicities induced by epidermal growth factor receptor tyrosine kinase inhibitor therapy in patients with lung adenocarcinoma', Journal of the European Academy of Dermatology and Venereology, vol. 37, no. 2, pp. 328-339. https://doi.org/10.1111/jdv.18703

Zinc deficiency associated with cutaneous toxicities induced by epidermal growth factor receptor tyrosine kinase inhibitor therapy in patients with lung adenocarcinoma. / Lu, Chun Wei; Pang, Jong Hwei Su; Ko, Yu Shien et al.
In: Journal of the European Academy of Dermatology and Venereology, Vol. 37, No. 2, 02.2023, p. 328-339.

Research output: Contribution to journal › Journal Article › peer-review

TY - JOUR

T1 - Zinc deficiency associated with cutaneous toxicities induced by epidermal growth factor receptor tyrosine kinase inhibitor therapy in patients with lung adenocarcinoma

AU - Lu, Chun Wei

AU - Pang, Jong Hwei Su

AU - Ko, Yu Shien

AU - Chang, Chih Jung

AU - Wang, Chuang Wei

AU - Chen, Wei Ti

AU - Chen, Chun Bing

AU - Hui, Rosaline Chung yee

AU - Hung, Shuen Iu

AU - Lu, Lai Ying

AU - Lu, Kun Lin

AU - Wang, Chih Liang

AU - Wu, Chiao En

AU - Hsu, Ping Chih

AU - Fang, Yueh Fu

AU - Li, Shih Hong

AU - Ko, How Wen

AU - Tseng, Li Chuan

AU - Shih, Feng Ya

AU - Chen, Mei Jun

AU - Chung, Wen Hung

PY - 2023/2

Y1 - 2023/2

N2 - PURPOSE: Cutaneous toxicities are common adverse effects following epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy. Zinc deficiency causes diverse diseases, including skin toxicities. Therefore, this study aimed to investigate the role of zinc deficiency in patients with EGFR-TKI-induced skin toxicities.EXPERIMENTAL DESIGN: This retrospective study enrolled 269 patients with diverse skin disorders who visited our hospital between January 2016 and December 2017. The skin toxicity severities and plasma zinc levels of 101 EGFR-TKI-treated cancer patients were analysed and compared with those of 43 non-EGFR-TKI-treated cancer patients and 125 patients without cancer but presenting cutaneous manifestations. Additionally, the role of zinc in erlotinib-induced skin eruptions was established in a 14-day-murine model. Clinical features were further evaluated following systemic zinc supplementation in EGFR-TKI-treated cancer patients.RESULTS: EGFR-TKI-treated patients demonstrated severe cutaneous manifestations and a significant decrease in plasma zinc levels than those of the control groups. The serum zinc level and Common Terminology Criteria for Adverse Events (CTCAE) 5.0 grading of EGFR-TKI-induced skin toxicities showed a significant negative correlation (r = -0.29; p < 0.0001). Moreover, erlotinib treatment decreased the plasma zinc levels and induced periorificial dermatitis in rats confirming zinc deficiency following EGFR-TKI treatment. Zinc supplementation to the EGFR-TKI-treated cancer patients showed a significant decrease in the CTCEA grading (p < 0.0005 for mucositis and p < 0.0.0001 for all other cases) after 8 weeks.CONCLUSIONS: Skin impairment following EGFR-TKI therapy could be ameliorated through zinc supplementation. Thus, zinc supplementation should be considered for cancer patients undergoing EGFR-TKI therapy.

AB - PURPOSE: Cutaneous toxicities are common adverse effects following epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy. Zinc deficiency causes diverse diseases, including skin toxicities. Therefore, this study aimed to investigate the role of zinc deficiency in patients with EGFR-TKI-induced skin toxicities.EXPERIMENTAL DESIGN: This retrospective study enrolled 269 patients with diverse skin disorders who visited our hospital between January 2016 and December 2017. The skin toxicity severities and plasma zinc levels of 101 EGFR-TKI-treated cancer patients were analysed and compared with those of 43 non-EGFR-TKI-treated cancer patients and 125 patients without cancer but presenting cutaneous manifestations. Additionally, the role of zinc in erlotinib-induced skin eruptions was established in a 14-day-murine model. Clinical features were further evaluated following systemic zinc supplementation in EGFR-TKI-treated cancer patients.RESULTS: EGFR-TKI-treated patients demonstrated severe cutaneous manifestations and a significant decrease in plasma zinc levels than those of the control groups. The serum zinc level and Common Terminology Criteria for Adverse Events (CTCAE) 5.0 grading of EGFR-TKI-induced skin toxicities showed a significant negative correlation (r = -0.29; p < 0.0001). Moreover, erlotinib treatment decreased the plasma zinc levels and induced periorificial dermatitis in rats confirming zinc deficiency following EGFR-TKI treatment. Zinc supplementation to the EGFR-TKI-treated cancer patients showed a significant decrease in the CTCEA grading (p < 0.0005 for mucositis and p < 0.0.0001 for all other cases) after 8 weeks.CONCLUSIONS: Skin impairment following EGFR-TKI therapy could be ameliorated through zinc supplementation. Thus, zinc supplementation should be considered for cancer patients undergoing EGFR-TKI therapy.

KW - Animals

KW - Mice

KW - Rats

KW - Adenocarcinoma of Lung/drug therapy

KW - ErbB Receptors

KW - Erlotinib Hydrochloride/adverse effects

KW - Exanthema/chemically induced

KW - Lung Neoplasms/drug therapy

KW - Mutation

KW - Protein Kinase Inhibitors/adverse effects

KW - Retrospective Studies

KW - Tyrosine Kinase Inhibitors/adverse effects

KW - Zinc/metabolism

UR - http://www.scopus.com/inward/record.url?scp=85142245009&partnerID=8YFLogxK

U2 - 10.1111/jdv.18703

DO - 10.1111/jdv.18703

M3 - 文章

C2 - 36366861

AN - SCOPUS:85142245009

SN - 0926-9959

VL - 37

SP - 328

EP - 339

JO - Journal of the European Academy of Dermatology and Venereology

JF - Journal of the European Academy of Dermatology and Venereology

IS - 2

ER -

Zinc deficiency associated with cutaneous toxicities induced by epidermal growth factor receptor tyrosine kinase inhibitor therapy in patients with lung adenocarcinoma

Abstract

Bibliographical note

Keywords

UN SDGs

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