Factors Influencing Imatinib-Induced Hepatotoxicity
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose Although imatinib-induced hepatotoxicity may aggravate the patient’s clinical condition and alter the treatment plan, the underlying mechanism of and factors influencing imatinibinduced hepatotoxicity have rarely been investigated. The purpose of this study was to investigate factors affecting on the incidence of hepatotoxicity within 90 days after starting imatinib treatment and time to onset of imatinib-induced hepatotoxicity. Materials and Methods We retrospectively evaluated the records of 177 patients receiving imatinib from October 2012 to September 2017. The analyzed factors included sex, age, body weight, body surface area, underlying disease, and concomitant drugs. Results The proportion of patients with hepatotoxicity within 90 days after imatinib administration was 33.9%. Proton pump inhibitors (PPIs) increased the incidence of hepatotoxicity approximately 3.8-fold and doubled the hazard of time to reach hepatotoxicity. Patients with liver disease or hepatitis B virus (HBV) carriers had a more than 8-fold higher risk of hepatotoxicity and a 5.2-fold increased hazard of hepatotoxicity compared to those without liver disease or HBV. Patients with body weight under 55 kg had a 2.2-fold higher risk for occurrence of hepatotoxicity. Patients with an imatinib dose > 400 mg had a 2.3-fold increased hazard of time to reach hepatotoxicity compared to those with an imatinib dose ! 400 mg. Conclusion The findings of this study suggest that the use of PPIs and presence of liver disease or HBV were associated with imatinib-induced hepatotoxicity. Thus, close liver function monitoring is recommended, especially in patients with liver impairment or using PPIs.
Abstract
Purpose Although imatinib-induced hepatotoxicity may aggravate the patient’s clinical condition and alter the treatment plan, the underlying mechanism of and factors influencing imatinibinduced hepatotoxicity have rarely been investigated. The purpose of this study was to investigate factors affecting on the incidence of hepatotoxicity within 90 days after starting imatinib treatment and time to onset of imatinib-induced hepatotoxicity. Materials and Methods We retrospectively evaluated the records of 177 patients receiving imatinib from October 2012 to September 2017. The analyzed factors included sex, age, body weight, body surface area, underlying disease, and concomitant drugs. Results The proportion of patients with hepatotoxicity within 90 days after imatinib administration was 33.9%. Proton pump inhibitors (PPIs) increased the incidence of hepatotoxicity approximately 3.8-fold and doubled the hazard of time to reach hepatotoxicity. Patients with liver disease or hepatitis B virus (HBV) carriers had a more than 8-fold higher risk of hepatotoxicity and a 5.2-fold increased hazard of hepatotoxicity compared to those without liver disease or HBV. Patients with body weight under 55 kg had a 2.2-fold higher risk for occurrence of hepatotoxicity. Patients with an imatinib dose > 400 mg had a 2.3-fold increased hazard of time to reach hepatotoxicity compared to those with an imatinib dose ! 400 mg. Conclusion The findings of this study suggest that the use of PPIs and presence of liver disease or HBV were associated with imatinib-induced hepatotoxicity. Thus, close liver function monitoring is recommended, especially in patients with liver impairment or using PPIs.
참고문헌 (29)
- Zhuang W, "Can therapeutic drug monitoring increase the safety of Imatinib in GIST patients", Cancer Med, 7, pp.317~324 (2018)
- Cohen MH, "Approval summary for imatinib mesylate capsules in the treatment of chronic myelogenous leukemia", Clin Cancer Res, 8, pp.935~942 (2002)
- Peng B, "Clinical pharmacokinetics of imatinib", Clin Pharmacokinet, 44, pp.879~894 (2005)
- O'Brien SG, "Imatinib compared with interferon and lowdose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia", N Engl J Med, 348, pp.994~1004 (2003)
- Dematteo RP, "Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour : a randomised, double-blind, placebo-controlled trial", Lancet, 373, pp.1097~1104 (2009)
- Johnson JR, "Approval summary : imatinib mesylate capsules for treatment of adult patients with newly diagnosed philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase", Clin Cancer Res, 9, pp.1972~1979 (2003)
- Mindikoglu AL, "Imatinib mesylate(gleevec)hepatotoxicity", Dig Dis Sci, 52, pp.598~601 (2007)
- Kong JH, "Early imatinib-mesylate-induced hepatotoxicity in chronic myelogenous leukaemia", Acta Haematol, 118, pp.205~208 (2007)
- Takikawa H, "Recent status of drug-induced liver injury and its problem in japan", Jpn Med Assoc J, 53, pp.243~247 (2010)
- Guilhot F, "Indications for imatinib mesylate therapy and clinical management", Oncologist, 9, pp.271~281 (2004)
- Shah RR, "Hepatotoxicity of tyrosine kinase inhibitors : clinical and regulatory perspectives", Drug Saf, 36, pp.491~503 (2013)
- "Highlights of prescribing information: Gleevec (imatinib mesylate)" (2018)[URL]
- Blanke CD, "Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase : S0033", J Clin Oncol, 26, pp.626~632 (2008)
- Larson RA, "Imatinib pharmacokinetics and its correlation with response and safety in chronic-phase chronic myeloid leukemia : a subanalysis of the IRIS study", Blood, 111, pp.4022~4028 (2008)
- Eadie LN, "Interaction of the efflux transporters ABCB1 and ABCG2 with imatinib, nilotinib, and dasatinib", Clin Pharmacol Ther, 95, pp.294~306 (2014)
- Burger H, "Pharmacokinetic resistance to imatinib mesylate : role of the ABC drug pumps ABCG2(BCRP)and ABCB1(MDR1)in the oral bioavailability of imatinib", Cell Cycle, 3, pp.1502~1505 (2004)
- Sharom FJ, "ABC multidrug transporters : structure, function and role in chemoresistance", Pharmacogenomics, 9, pp.105~127 (2008)
- Cho S, "Effects of concomitant medication use on gefitinib-induced hepatotoxicity", J Clin Pharmacol, 58, pp.263~268 (2018)
- Lodato F, "Proton pump inhibitors in cirrhosis : tradition or evidence based practice", World J Gastroenterol, 14, pp.2980~2985 (2008)
- Hodges LM, "Very important pharmacogene summary : ABCB1(MDR1, P-glycoprotein)", Pharmacogenet Genomics, 21, pp.152~161 (2011)
- Crossman LC, "hOCT 1 and resistance to imatinib", Blood, 106, pp.1133~1134 (2005)
- Thomas J, "Active transport of imatinib into and out of cells : implications for drug resistance", Blood, 104, pp.3739~3745 (2004)
- Bourdet DL, "Differential substrate and inhibitory activities of ranitidine and famotidine toward human organic cation transporter 1(hOCT1; SLC22A1), hOCT2(SLC22A2), and hOCT3(SLC22A3)", J Pharmacol Exp Ther, 315, pp.1288~1297 (2005)
- Haouala A, "Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib, and nilotinib", Blood, 117, pp.e75~e87 (2011)
- White DL, "OCT-1-mediated influx is a key determinant of the intracellular uptake of imatinib but not nilotinib(AMN107) : reduced OCT-1 activity is the cause of low in vitro sensitivity to imatinib", Blood, 108, pp.697~704 (2006)
- Budha NR, "Drug absorption interactions between oral targeted anticancer agents and PPIs : is pH-dependent solubility the Achilles heel of targeted therapy", Clin Pharmacol Ther, 92, pp.203~213 (2012)
- Deininger MW, "Specific targeted therapy of chronic myelogenous leukemia with imatinib", Pharmacol Rev, 55, pp.401~423 (2003)
- Dutreix C, "Pharmacokinetic interaction between ketoconazole and imatinib mesylate(Glivec)in healthy subjects", Cancer Chemother Pharmacol, 54, pp.290~294 (2004)
- Bolton AE, "Effect of rifampicin on the pharmacokinetics of imatinib mesylate(Gleevec, STI571)in healthy subjects", Cancer Chemother Pharmacol, 53, pp.102~106 (2004)