Risk factors for erlotinib-induced hepatotoxicity: a retrospective follow-up study
- 주제(키워드) Erlotinib , Hepatotoxicity , CYP3A4 inducers , H2-antagonist , Proton pump inhibitor
- 주제(기타) Oncology
- 설명문(일반) [Kim, Min Kyoung; Gwak, Hye Sun] Ewha Womans Univ, Grad Sch Converging Clin & Publ Hlth, Seoul 03760, South Korea; [Kim, Min Kyoung; Cho, Yoon Sook; Jang, Hong Won; Han, Ji Min] Seoul Natl Univ Hosp, Dept Pharm, Seoul 03080, South Korea; [Yee, Jeong; Han, Ji Min; Gwak, Hye Sun] Ewha Womans Univ, Coll Pharm, 52 Ewhayeodae Gil, Seoul 03760, South Korea; [Yee, Jeong; Han, Ji Min; Gwak, Hye Sun] Ewha Womans Univ, Div Life & Pharmaceut Sci, 52 Ewhayeodae Gil, Seoul 03760, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 BMC
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000156139
- 본문언어 영어
- Published As http://dx.doi.org/10.1186/s12885-018-4891-7
초록/요약
BackgroundErlotinib is a drug used for the treatment of non-small cell lung cancer (NSCLC) and pancreatic cancer. Severe hepatotoxicity was observed in 4% to 31% of patients receiving erlotinib treatment prompting delay or termination of treatment. Only a few factors related to hepatotoxicity of erlotinib have been reported. No study has investigated the role of concomitant medications and erlotinib-induced hepatotoxicity. The aim of this study was to investigate the association between erlotinib-induced hepatotoxicity and various factors including concomitant medications in patients with NSCLC and pancreatic cancer.MethodsFrom January 2014 to June 2017, a retrospective study was conducted in patients with NSCLC and pancreatic cancer, who were treated with erlotinib. Various data were reviewed, including sex, age, body weight, height, body surface area (BSA), underlying disease, Eastern Cooperative Oncology Group (ECOG) Performance Status (PS), smoking history, erlotinib dose, EGFR mutation, and concomitant drugs.ResultsThe incidence of grade 2 or higher hepatotoxicity in the study group of patients was 17.2%. Multivariate analysis showed a 2.7-fold increase in hepatotoxicity with the concomitant use of CYP3A4 inducers. In NSCLC patients, co-administration of H2-antagonist/PPI increased hepatotoxicity 3.5-fold. Among the demographic factors, liver metastasis and age65years were significant risk factors in all study patients and NSCLC patients, respectively; the attributable risks for liver metastasis and age were 46.3% and 71.8%, respectively. Subgroup analysis using pancreatic cancer patients yielded marginally significant results with CYP3A4 inducers and erlotinib-induced hepatotoxicity. Liver metastasis and CYP3A4 inducers also shortened time to hepatotoxicity 2.1 and 2.3-fold, respectively.ConclusionsOur study showed that concomitant use of CYP3A4 inducers and H2-antagonist/PPI, liver metastasis, and age65 were associated with erlotinib-induced hepatotoxicity. Thus, close monitoring of liver function is recommended, especially in patients using CYP3A4 inducers and anti-acid secreting agents.
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