Factors affecting time to reach and recover from gefitinib-induced hepatotoxicity
- 주제(키워드) gefitinib , hepatotoxicity , time to reach hepatotoxicity , time to recover from hepatotoxicity
- 주제(기타) Oncology; Pharmacology & Pharmacy
- 설명문(일반) [Park, Yoon Hee; Cho, Soyeon; Yee, Jeong; Rhie, Sandy Jeong; Gwak, Hye Sun] Ewha Womans Univ, Coll Pharm, Div Life & Pharmaceut Sci, 52 Ewhayeodae Gil, Seoul 03760, South Korea; [Park, Yoon Hee; Cho, Soyeon; Kim, Jae Youn] Asan Med Ctr, Dept Pharm, Seoul, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 LIPPINCOTT WILLIAMS & WILKINS
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000151585
- 본문언어 영어
- Published As http://dx.doi.org/10.1097/CAD.0000000000000622
초록/요약
Gefitinib is an oral tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR) for non-small-cell lung cancer with EGFR mutations. Although a few studies have analyzed the causes of gefitinib-induced hepatotoxicity, research focusing on the time intervals before and after hepatotoxicity has yet to be reported. Therefore, this study investigated two types of factors: the time to reach gefitinib-induced hepatotoxicity and the time for recovery. From January 2013 to December 2014, a retrospective study was carried out on 473 non-small-cell lung cancer patients who were treated with gefitinib. The following data were collected: sex, age, body weight, height, body surface area, underlying disease, Eastern Cooperative Oncology Group Performance Status, smoking history, gefitinib dose, EGFR mutation, and concomitant drugs. Multivariate models showed that patients with mutations in exon 19 had around two-fold higher hepatotoxicity (grade 2). Use of CYP3A4 inhibitors and smoking shortened time to hepatotoxicity approximate to 5-2-fold, respectively, whereas mutations in exon 21 prolonged time to hepatotoxicity by about 2.4-fold. Termination of gefitinib therapy showed 3.8-fold faster recovery. Our study showed that the concomitant use of CYP3A4 inhibitors, smoking, and exon 21 affected the time to reach gefitinib-induced hepatotoxicity. Among the factors examined in this study including hepatotonic use and gefitinib termination, only cessation of gefitinib therapy significantly accelerated recovery.
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