Cancer Research and Treatment

Original Articles

Factors Influencing Imatinib-Induced Hepatotoxicity: Ji Min Han, Jeong Yee, Yoon Sook Cho, Hye Sun Gwak; Cancer Res Treat. 2020;52(1):181-188. Published online June 26, 2019; DOI: https://doi.org/10.4143/crt.2019.131

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.

Citations

Citations to this article as recorded by

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Pharmaceutical Development and Technology.2024; 29(1): 52. CrossRef
The prevalence of hepatic and thyroid toxicity associated with imatinib treatment of chronic myeloid leukaemia: a systematic review
Mansour Tobaiqy, Nawal Helmi, Katie MacLure, Sylvia Saade
International Journal of Clinical Pharmacy.2024; 46(2): 368. CrossRef
Tyrosine kinase inhibitors can activate the NLRP3 inflammasome in myeloid cells through lysosomal damage and cell lysis
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Comparison of Native Escherichia coli L-Asparaginase versus Pegylated Asparaginase, in Combination with Ifosfamide, Methotrexate, Etoposide, and Prednisolone, in Extranodal NK/T-Cell Lymphoma, Nasal Type: Hyun Jee Kim, Chan-Young Ock, Tae Min Kim, Sung Hee Lee, Ju-Yeun Lee, Sun hoi Jung, Yoon Sook Cho, Miso Kim, Bhumsuk Keam, Dong-Wan Kim, Il Han Kim, Dae Seog Heo; Cancer Res Treat. 2018;50(3):670-680. Published online July 3, 2017; DOI: https://doi.org/10.4143/crt.2017.051

Abstract PDF Supplementary Material PubReader ePub

Purpose
The aim of this study was to compare asparaginase-related toxicities in two asparaginase preparations, namely native Escherichia coli L-asparaginase (L-ASP) and pegylated asparaginase (PEG-ASP) in combination with ifosfamide, methotrexate, etoposide, and prednisolone (IMEP) in natural killer (NK)/T-cell lymphoma (NTCL).
Materials and Methods
A total of 41 NTCL patients who received IMEP plus native E. coli L-ASP or PEG-ASP at Seoul National University Hospital were included in this study between January 2013 and March 2016. IMEP/ASP treatment consisted of ifosfamide, methotrexate, etoposide, plus native E. coli L-ASP (6,000 IU/m² on days 1, 3, 5, 7, 9, and 11) or PEG-ASP (2,500 IU/m² on day 1) every 3 weeks. ASP-related toxicities, toxicity patterns, length of hospital stay, and clinical outcomes were compared between the different treatment groups.
Results
The frequency of ASP-related toxicities was similar between the IMEP plus native E. coli L-ASP group and the PEG-ASP group apart from hypofibrinogenemia (native E. coli L-ASP vs. PEG-ASP group, 86.4% vs. 36.8%; p=0.001). Although post-treatment transaminase and albumin levels were significantly high and low, respectively, hepatotoxicity gradients before and after treatment did not differ significantly between the groups. Since PEG-ASP was given at an outpatient clinic in some patients, length of hospital stay was significantly shorter in the IMEP plus PEG-ASP group (median, 4.0 vs. 6.0 days; p=0.002). A favorable tendency of clinical outcomes was observed in NTCL patients treated with IMEP plus PEG-ASP (complete remission rate, 73.7% vs. 45.5%; p=0.067).
Conclusion
IMEP plus PEG-ASP showed similar ASP-related toxicities, shorter length of hospital stay, and a trend towards improved clinical outcomes compared with IMEP plus native E. coli L-ASP in NTCL.

Citations

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