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

被引:8
|
作者
Lu, Chun-Wei [1 ,2 ,3 ,4 ,5 ,6 ,7 ,8 ]
Pang, Jong-Hwei Su [8 ,9 ]
Ko, Yu-Shien [7 ,8 ,10 ,11 ]
Chang, Chih-Jung [1 ,2 ,3 ,4 ,5 ,6 ,12 ,13 ,14 ]
Wang, Chuang-Wei [1 ,2 ,3 ,4 ,5 ,6 ,15 ,16 ,17 ]
Chen, Wei-Ti [1 ,2 ,3 ,4 ,5 ,6 ,7 ,17 ]
Chen, Chun-Bing [1 ,2 ,3 ,4 ,5 ,6 ,8 ,15 ,16 ,17 ,18 ,19 ]
Hui, Rosaline Chung-yee [1 ,2 ,3 ,4 ,5 ,6 ,7 ]
Hung, Shuen-Iu [12 ,20 ]
Lu, Lai-Ying [1 ,2 ,3 ,7 ]
Lu, Kun Lin [2 ]
Wang, Chih-Liang [7 ,21 ,22 ]
Wu, Chiao-En [7 ,22 ,23 ]
Hsu, Ping-Chih [7 ,21 ,22 ]
Fang, Yueh-Fu [7 ,21 ,22 ]
Li, Shih-Hong [7 ,21 ,22 ]
Ko, How-Wen [7 ,21 ,22 ]
Tseng, Li-Chuan [24 ]
Shih, Feng-Ya [24 ]
Chen, Mei-Jun [1 ,4 ]
Chung, Wen-Hung [1 ,2 ,3 ,4 ,5 ,6 ,7 ]
机构
[1] Chang Gung Mem Hosp, Dept Dermatol, Linkou, Taiwan
[2] Chang Gung Mem Hosp, Dept Dermatol, Taipei, Taiwan
[3] Chang Gung Mem Hosp, Dept Dermatol, Keelung, Taiwan
[4] Chang Gung Mem Hosp, Drug Hypersensit Clin & Res Ctr, Linkou, Taiwan
[5] Chang Gung Mem Hosp, Drug Hypersensit Clin & Res Ctr, Taipei, Taiwan
[6] Chang Gung Mem Hosp, Drug Hypersensit Clin & Res Ctr, Keelung, Taiwan
[7] Chang Gung Univ, Coll Med, Taoyuan, Taiwan
[8] Chang Gung Univ, Coll Med, Grad Inst Clin Med Sci, Taoyuan, Taiwan
[9] Chang Gung Mem Hosp, Dept Phys Med & Rehabil, Linkou, Taiwan
[10] Chang Gung Mem Hosp, Cardiovasc Div, Linkou, Taiwan
[11] Chang Gung Mem Hosp, Microscope Core Lab, Linkou, Taiwan
[12] Xiamen Chang Gung Hosp, Allergol Consortium, Xiamen, Fujian, Peoples R China
[13] Xiamen Chang Gung Hosp, Med Res Ctr, Xiamen, Fujian, Peoples R China
[14] Huaqiao Univ, Sch Med, Quanzhou, Fujian, Peoples R China
[15] Chang Gung Mem Hosp, Canc Vaccine & Immune Cell Therapy Core Lab, Linkou, Taiwan
[16] Chang Gung Mem Hosp, Chang Gung Immunol Consortium, Linkou, Taiwan
[17] Xiamen Chang Gung Hosp, Dept Dermatol, Xiamen, Peoples R China
[18] Chang Gung Univ, Chang Gung Immunol Consortium, Taoyuan, Taiwan
[19] Chang Gung Mem Hosp, Whole Genome Res Core Lab Human Dis, Keelung, Taiwan
[20] Natl Yang Ming Univ, Sch Med, Inst Pharmacol, Taipei, Taiwan
[21] Chang Gung Mem Hosp, Div Thorac Med, Linkou, Taiwan
[22] Chang Gung Mem Hosp, Dept Internal Med, Linkou, Taiwan
[23] Chang Gung Mem Hosp, Div Hematol Oncol, Linkou, Taiwan
[24] Chang Gung Mem Hosp, Dept Oncol Case Management, Taoyuan, Taiwan
关键词
NECROLYTIC MIGRATORY ERYTHEMA; SKIN; TRANSPORTER; ERLOTINIB; RISK;
D O I
10.1111/jdv.18703
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
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.
引用
收藏
页码:328 / 339
页数:12
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