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1
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Purwar S, Fatima A, Bhattacharyya H, Simhachalam Kutikuppala LV, Cozma MA, Srichawla BS, Komer L, Nurani KM, Găman MA. Toxicity of targeted anticancer treatments on the liver in myeloproliferative neoplasms. World J Hepatol 2023; 15:1021-1032. [PMID: 37900211 PMCID: PMC10600697 DOI: 10.4254/wjh.v15.i9.1021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 08/06/2023] [Accepted: 08/18/2023] [Indexed: 09/22/2023] Open
Abstract
The liver has a central role in metabolism, therefore, it is susceptible to harmful effects of ingested medications (drugs, herbs, and nutritional supplements). Drug-induced liver injury (DILI) comprises a range of unexpected reactions that occur after exposure to various classes of medication. Even though most cases consist of mild, temporary elevations in liver enzyme markers, DILI can also manifest as acute liver failure in some patients and can be associated with mortality. Herein, we briefly review available data on DILI induced by targeted anticancer agents in managing classical myeloproliferative neoplasms: Chronic myeloid leukemia, polycythemia vera, essential thrombocythemia, and myelofibrosis.
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Affiliation(s)
- Shubhrat Purwar
- Department of Internal Medicine, Grant Government Medical College, Mumbai 400008, Maharashtra, India
| | - Anam Fatima
- Department of Internal Medicine, Pandit Jawaharlal Nehru Memorial Medical College, Raipur 492001, Chhattisgarh, India
| | | | | | - Matei-Alexandru Cozma
- Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy, Bucharest 050474, Romania
- Department of Gastroenterology, Colentina Clinical Hospital, Bucharest 020125, Romania
| | - Bahadar Singh Srichawla
- Department of Neurology, University of Massachusetts Chan Medical School, Worcester, MA 01655, United States
| | - Leah Komer
- Department of Psychiatry, University of Toronto, Toronto M5G 1V7, Ontario, Canada
| | | | - Mihnea-Alexandru Găman
- Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy, Bucharest 050474, Romania
- Department of Hematology, Center of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, Bucharest 022328, Romania.
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Parrack PH, Zucker SD, Zhao L. Liver Pathology Related to Onco-Therapeutic Agents. Surg Pathol Clin 2023; 16:499-518. [PMID: 37536885 DOI: 10.1016/j.path.2023.04.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/05/2023]
Abstract
Oncotherapeutic agents can cause a wide range of liver injuries from elevated liver functions tests to fulminant liver failure. In this review, we emphasize a newer generation of drugs including immune checkpoint inhibitors, protein kinase inhibitors, monoclonal antibodies, and hormonal therapy. A few conventional chemotherapy agents are also discussed.
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Affiliation(s)
- Paige H Parrack
- Department of Pathology, Brigham and Women's Hospital, 75 Francis street, Boston, MA, 02115, USA; Harvard Medical School
| | - Stephen D Zucker
- Harvard Medical School; Department of Medicine, Brigham and Women's Hospital, 75 Francis street, Boston, MA, 02115, USA
| | - Lei Zhao
- Department of Pathology, Brigham and Women's Hospital, 75 Francis street, Boston, MA, 02115, USA; Harvard Medical School.
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3
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Hwang WL, Chen TC, Lin HY, Chang MC, Hsiao PC, Bai LY, Kuo CY, Chen YC, Liu TC, Gau JP, Wang PN, Hwang WS, Kuo MC, Liu CY, Liu YC, Ma MC, Su NW, Wang CC, Wu YY, Yao M, Yeh SP, Cheng HW, Lee YM, Ku FC, Tang JL. NOVEL-1st: an observational study to assess the safety and efficacy of nilotinib in newly diagnosed patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase in Taiwan. Int J Hematol 2022; 115:704-712. [PMID: 35212915 DOI: 10.1007/s12185-022-03311-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 02/09/2022] [Accepted: 02/09/2022] [Indexed: 11/28/2022]
Abstract
Nilotinib has been approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). However, the real-world evidence of nilotinib in newly diagnosed untreated Ph+ CML-CP is limited in Taiwan. The NOVEL-1st study was a non-interventional, multi-center study collecting long-term safety and effectiveness data in patients with newly diagnosed and untreated Ph+ CML-CP receiving nilotinib. We enrolled 129 patients from 11 hospitals. Overall, 1,466 adverse events (AEs) were reported; among these, 151 were serious and 524 were nilotinib-related. Common hematological AEs were thrombocytopenia (31.0%), anemia (20.9%), and leukopenia (14.0%); common nilotinib-related AEs were thrombocytopenia (29.5%), anemia (14.7%), and leukopenia (12.4%). Early molecular response, defined as BCR-ABL ≤ 10% at Month 3, was seen in 87.6% of patients. By 36 months, the cumulative rates of complete hematologic response, complete cytogenetic response, major molecular response, molecular response 4.0-log reduction, and molecular response 4.5-log reduction were 98.5, 92.5, 85.8, 65.0, and 45.0%, respectively. Nilotinib is effective and well-tolerated in patients with newly diagnosed Ph+ CML-CP in the real-world setting. Long-term holistic care and a highly tolerable AE profile may contribute to good treatment outcomes in Ph+ CML-CP under first-line treatment with nilotinib.
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Affiliation(s)
- Wen-Li Hwang
- Taichung Veterans General Hospital, Taichung, Taiwan.,Asia University Hospital, Taichung, Taiwan
| | | | | | | | | | - Li-Yuan Bai
- China Medical University Hospital, Taichung, Taiwan
| | - Ching-Yuan Kuo
- Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | | | - Ta-Chih Liu
- Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan.,Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan
| | - Jyh-Pyng Gau
- Taipei Veterans General Hospital, Taipei, Taiwan
| | - Po-Nan Wang
- Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Wei-Shou Hwang
- Chung Shan Medical University Hospital, Taichung, Taiwan
| | | | - Chun-Yu Liu
- Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Chang Liu
- Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan
| | - Ming-Chun Ma
- Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Nai-Wen Su
- Mackay Memorial Hospital, Taipei, Taiwan
| | | | - Yi-Ying Wu
- Tri-Service General Hospital, Taipei, Taiwan
| | - Ming Yao
- National Taiwan University Hospital, Taipei, Taiwan
| | - Su-Peng Yeh
- China Medical University Hospital, Taichung, Taiwan
| | | | | | | | - Jih-Luh Tang
- National Taiwan University Hospital, Taipei, Taiwan.
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4
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Wang Z, Wang X, Wang Z, Feng Y, Jia Y, Jiang L, Xia Y, Cao J, Liu Y. Comparison of Hepatotoxicity Associated With New BCR-ABL Tyrosine Kinase Inhibitors vs Imatinib Among Patients With Chronic Myeloid Leukemia: A Systematic Review and Meta-analysis. JAMA Netw Open 2021; 4:e2120165. [PMID: 34292334 PMCID: PMC8299317 DOI: 10.1001/jamanetworkopen.2021.20165] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
IMPORTANCE Although BCR-ABL fusion oncoprotein tyrosine kinase inhibitors (BCR-ABL TKIs) can substantially improve the survival rate of chronic myeloid leukemia (CML), they are clinically accompanied by severe hepatotoxicity. OBJECTIVE To compare the relative risk (RR) of hepatotoxicity of new-generation BCR-ABL TKIs with that of imatinib, and to provide an overall assessment of the clinical benefit. DATA SOURCES PubMed, Embase, Cochrane library databases, and ClinicalTrials.gov were searched for clinical trials published between January 2000 and April 2020. STUDY SELECTION Study selection was conducted independently by 2 investigators according to the inclusion and exclusion criteria published previously in the protocol: only randomized phase 2 or phase 3 clinical trials that compared bosutinib, dasatinib, nilotinib, or ponatinib with imatinib were included. Among the 2666 records identified, 9 studies finally fulfilled the established criteria. DATA EXTRACTION AND SYNTHESIS Two investigators extracted study characteristics and data independently using a standardized data extraction form. Data were extracted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. When substantial heterogeneity was observed, pooled estimates were calculated based on the random-effect model; otherwise, the fixed-effect model was used. MAIN OUTCOMES AND MEASURES Data extracted included study characteristics, baseline patient information, interventions and data on all-grade and high-grade (grades 3 and 4) elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, overall survival, and major molecular response (MMR). The RRs and 95% CIs were calculated using the inverse variance method. RESULTS Nine trials involving 3475 patients were analyzed; the median (range) age was 49 (18-91) years; 2059 (59.2%) were male patients. Increased risks were observed for each new-generation TKI except for dasatinib. Patients receiving new-generation TKIs were more likely to experience all grades of ALT elevation (pooled RR, 2.89; 95% CI, 1.78-4.69; P < .001) and grades 3 and 4 ALT elevation (pooled RR, 4.36; 95% CI, 2.00-9.50; P < .001) compared with those receiving imatinib. Patients receiving new-generation TKIs were also more likely to experience all grades of AST elevation (pooled RR, 2.20; 95% CI, 1.63-2.98; P < .001) and grades 3 and 4 AST elevation (pooled RR, 2.65; 95% CI, 1.59-4.42; P < .001) compared with those receiving imatinib. New-generation TKIs were associated with a significantly higher rate of MMR at 1 year compared with imatinib (pooled RR, 1.59; 95% CI, 1.44-1.75; P < .001). No statistical difference in overall survival at 1 year was found between new-generation TKIs and imatinib (pooled RR, 1.00; 95% CI, 1.00-1.01; P = .33). CONCLUSIONS AND RELEVANCE When compared to imatinib, bosutinib, nilotinib, and ponatinib had higher relative risks of hepatotoxicity. Treatment with new-generation TKIs was associated with a higher MMR rate at 1 year but not with 1-year overall survival.
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MESH Headings
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Alanine Transaminase/blood
- Aniline Compounds/adverse effects
- Aspartate Aminotransferases/blood
- Chemical and Drug Induced Liver Injury/etiology
- Dasatinib/adverse effects
- Female
- Humans
- Imatinib Mesylate/adverse effects
- Imidazoles/adverse effects
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
- Male
- Middle Aged
- Nitriles/adverse effects
- Oncogene Proteins v-abl/drug effects
- Protein Kinase Inhibitors/adverse effects
- Protein-Tyrosine Kinases/antagonists & inhibitors
- Proto-Oncogene Proteins c-bcr/drug effects
- Pyridazines/adverse effects
- Pyrimidines/adverse effects
- Quinolines/adverse effects
- Risk
- Young Adult
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Affiliation(s)
- Zhe Wang
- School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, China
| | - Xiaoyu Wang
- School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, China
| | - Zhen Wang
- School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, China
| | - Yuyi Feng
- School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, China
| | - Yaqin Jia
- School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, China
| | - Lili Jiang
- School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, China
| | - Yangliu Xia
- School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, China
| | - Jun Cao
- Department of Occupational and Environmental Health, Dalian Medical University, Dalian, China
| | - Yong Liu
- School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, China
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5
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Machine Learning Approaches to Predict Hepatotoxicity Risk in Patients Receiving Nilotinib. Molecules 2021; 26:molecules26113300. [PMID: 34072626 PMCID: PMC8198751 DOI: 10.3390/molecules26113300] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 05/25/2021] [Accepted: 05/28/2021] [Indexed: 12/24/2022] Open
Abstract
Background: Although nilotinib hepatotoxicity can cause severe clinical conditions and may alter treatment plans, risk factors affecting nilotinib-induced hepatotoxicity have not been investigated. This study aimed to elucidate the factors affecting nilotinib-induced hepatotoxicity. Methods: This retrospective cohort study was performed on patients using nilotinib from July of 2015 to June of 2020. We estimated the odds ratio and adjusted odds ratio from univariate and multivariate analyses, respectively. Several machine learning models were developed to predict risk factors of hepatotoxicity occurrence. The area under the curve (AUC) was analyzed to assess clinical performance. Results: Among 353 patients, the rate of patients with grade I or higher hepatotoxicity after nilotinib administration was 40.8%. Male patients and patients who received nilotinib at a dose of ≥300 mg had a 2.3-fold and a 3.5-fold increased risk for hepatotoxicity compared to female patients and compared with those who received <300 mg, respectively. H2 blocker use decreased hepatotoxicity by 11.6-fold. The area under the curve (AUC) values of machine learning methods ranged between 0.61–0.65 in this study. Conclusion: This study suggests that the use of H2 blockers was a reduced risk of nilotinib-induced hepatotoxicity, whereas male gender and a high dose were associated with increased hepatotoxicity.
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6
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Meng L, Zhao P, Hu Z, Ma W, Niu Y, Su J, Zhang Y. Nilotinib, A Tyrosine Kinase Inhibitor, Suppresses the Cell Growth and Triggers Autophagy in Papillary Thyroid Cancer. Anticancer Agents Med Chem 2021; 22:596-602. [PMID: 33797387 DOI: 10.2174/1871520621666210402110331] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Revised: 02/23/2021] [Accepted: 03/08/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Papillary thyroid carcinoma (PTC) represents for the most common thyroid cancer. Until recently, treatment options for PTC patients are limited. Nilotinib is the second-generation tyrosine kinase inhibitor, and has been widely used in the treatment of chronic myeloid leukemia (CML). OBJECTIVES We aimed to explore whether nilotinib is effective in PTC cancer progression and the underlying mechanisms. METHODS In this study, the three human PTC cell lines (KTC-1, BCPAP, and TPC1) were used to verify the effects of nilotinib on cell growth. The half maximal inhibitory concentration (IC50) was calculated according to the growth curve post nilotinib treatment at different concentrations. Cell counting kit-8 and colony formation analysis were used to monitor cell growth after nilotinib treatment. Cell apoptosis and autophagy related proteins and phosphorylation of PI3K/Akt/mTOR were detected by Western blotting analysis. RESULTS Nilotinib treatment can effectively inhibit PTC cell growth, which was accompanied by increase of apoptosis and induction of autophagy. Mechanistically, nilotinib treatment repressed the phosphorylation of PI3K/Akt/mTOR pathway. CONCLUSION Collectively, our results demonstrated that nilotinib may display anti-tumor effect against PTC via inhibiting of PI3K/Akt/mTOR pathway and inducing apoptosis and autophagy.
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Affiliation(s)
- Lei Meng
- Three Departments of Abdominal Surgery, Xingtai First Hospital, No.376 Shunde Road, Qiaodong District, Xingtai 054000, Hebei. China
| | - Pengxin Zhao
- The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang 050000, Hebei. China
| | - Zhigang Hu
- The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang 050000, Hebei. China
| | - Weiyuan Ma
- The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang 050000, Hebei. China
| | - Yong Niu
- Quyang People's Hospital, Taihang Road, Quyang County, Baoding 071000, Hebei. China
| | - Jingwei Su
- Quyang People's Hospital, Taihang Road, Quyang County, Baoding 071000, Hebei. China
| | - Yubo Zhang
- The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang 050000, Hebei. China
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Nelson RS, Seligson ND, Bottiglieri S, Carballido E, Cueto AD, Imanirad I, Levine R, Parker AS, Swain SM, Tillman EM, Hicks JK. UGT1A1 Guided Cancer Therapy: Review of the Evidence and Considerations for Clinical Implementation. Cancers (Basel) 2021; 13:1566. [PMID: 33805415 PMCID: PMC8036652 DOI: 10.3390/cancers13071566] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 03/18/2021] [Accepted: 03/19/2021] [Indexed: 02/07/2023] Open
Abstract
Multi-gene assays often include UGT1A1 and, in certain instances, may report associated toxicity risks for irinotecan, belinostat, pazopanib, and nilotinib. However, guidance for incorporating UGT1A1 results into therapeutic decision-making is mostly lacking for these anticancer drugs. We summarized meta-analyses, genome-wide association studies, clinical trials, drug labels, and guidelines relating to the impact of UGT1A1 polymorphisms on irinotecan, belinostat, pazopanib, or nilotinib toxicities. For irinotecan, UGT1A1*28 was significantly associated with neutropenia and diarrhea, particularly with doses ≥ 180 mg/m2, supporting the use of UGT1A1 to guide irinotecan prescribing. The drug label for belinostat recommends a reduced starting dose of 750 mg/m2 for UGT1A1*28 homozygotes, though published studies supporting this recommendation are sparse. There was a correlation between UGT1A1 polymorphisms and pazopanib-induced hepatotoxicity, though further studies are needed to elucidate the role of UGT1A1-guided pazopanib dose adjustments. Limited studies have investigated the association between UGT1A1 polymorphisms and nilotinib-induced hepatotoxicity, with data currently insufficient for UGT1A1-guided nilotinib dose adjustments.
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Affiliation(s)
- Ryan S. Nelson
- Department of Consultative Services, ARUP Laboratories, Salt Lake City, UT 84108, USA;
- Department of Individualized Cancer Management, Moffitt Cancer Center, Tampa, FL 33612, USA;
| | - Nathan D. Seligson
- Department of Pharmacotherapy and Translational Research, The University of Florida, Jacksonville, FL 32610, USA;
- Department of Hematology and Oncology, Nemours Children’s Specialty Care, Jacksonville, FL 32207, USA
| | - Sal Bottiglieri
- Department of Pharmacy, Moffitt Cancer Center, Tampa, FL 33612, USA;
| | - Estrella Carballido
- Department of Oncological Sciences, University of South Florida, Tampa, FL 33612, USA; (E.C.); (I.I.); (R.L.)
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA
| | - Alex Del Cueto
- Department of Individualized Cancer Management, Moffitt Cancer Center, Tampa, FL 33612, USA;
| | - Iman Imanirad
- Department of Oncological Sciences, University of South Florida, Tampa, FL 33612, USA; (E.C.); (I.I.); (R.L.)
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA
| | - Richard Levine
- Department of Oncological Sciences, University of South Florida, Tampa, FL 33612, USA; (E.C.); (I.I.); (R.L.)
- Department of Satellite and Community Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA
| | | | - Sandra M. Swain
- Georgetown University Medical Center, MedStar Health, Washington, DC 20007, USA;
| | - Emma M. Tillman
- Indiana University School of Medicine, Indianapolis, IN 46202, USA;
| | - J. Kevin Hicks
- Department of Individualized Cancer Management, Moffitt Cancer Center, Tampa, FL 33612, USA;
- Department of Oncological Sciences, University of South Florida, Tampa, FL 33612, USA; (E.C.); (I.I.); (R.L.)
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8
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Goda AE, Elsisi AE, Sokkar SS, Abdelrazik NM. Enhanced in vivo targeting of estrogen receptor alpha signaling in murine mammary adenocarcinoma by nilotinib/rosuvastatin novel combination. Toxicol Appl Pharmacol 2020; 404:115185. [PMID: 32771489 DOI: 10.1016/j.taap.2020.115185] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 07/19/2020] [Accepted: 08/04/2020] [Indexed: 02/06/2023]
Abstract
The development of resistance to endocrine therapy of estrogen receptor alpha (ERα)-positive breast cancer is inevitable, necessitating the introduction of alternative treatment strategies. Therefore, the current study was carried out to investigate the in vivo efficacy and tolerability of nilotinib/rosuvastatin novel combination against ERα-positive breast carcinoma. Results showed that treatment of tumor-bearing mice with nilotinib/rosuvastatin exerted a significant antitumor activity. Mechanistically, the combination treatment efficiently inhibited the in vivo ERα protein expression, whereas ERα mRNA levels were unaffected suggesting a posttranslational regulation. In addition, the combination treatment markedly downregulated the expression of two ERα downstream target genes: C3 and pS2 confirming the inhibition of ERα signaling in vivo. Further, nilotinib/rosuvastatin combination strongly induced apoptosis evidenced by a marked caspase-3 cleavage and downregulation of tumor nitric oxide levels. Moreover, histopathology showed significant declines in mitotic figures and tumor giant cells implying the in vivo capability of the combination treatment to interfere with cancer cell proliferation and persistence. Of note, the combination treatment abrogated nilotinib-induced hypercholesterolemia and did not adversely affect the liver function or body weight. Overall, the present study provided evidences that warrant further assessment of nilotinib/rosuvastatin combination as an alternative therapeutic modality for ERα-positive breast cancer.
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Affiliation(s)
- Ahmed E Goda
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt.
| | - Alaa E Elsisi
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt
| | - Samia S Sokkar
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt
| | - Noha M Abdelrazik
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt
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9
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Yang H, Sung PS, Jung ES, Cho S, Bae SH, Kim DW. Nilotinib-Induced Immune-Mediated Liver Injury: Corticosteroid as a Possible Therapeutic Option. Front Oncol 2020; 10:1160. [PMID: 32754445 PMCID: PMC7367179 DOI: 10.3389/fonc.2020.01160] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Accepted: 06/08/2020] [Indexed: 12/12/2022] Open
Abstract
Introduction: Nilotinib is a BCR-ABL tyrosine kinase inhibitor approved for chronic myeloid leukemia. We present a case of severe immune-mediated liver injury by nilotinib treatment. Case report: A 59-year-old woman was referred to the liver clinic because of elevated liver enzyme levels. One year prior, she was diagnosed as having chronic myeloid leukemia and treated with nilotinib therapy. The level of aspartate aminotransferase and alanine aminotransferase were 578 IU/L and 499 IU/L, respectively. Percutaneous needle liver biopsy showed extensive centrilobular infiltration of immune cells and destruction of the lobular architecture with minimal inflammation in the portal triad. Immunohistochemical staining showed that many CD8+ T cells and CD56+ cells infiltrated the site of inflammation. Multicolor fluorescence-activated cell-sorting analysis revealed that a considerable number of intrahepatic CD8+ T cells showed an activated phenotype compared with the healthy control. She was diagnosed with nilotinib-induced, immune-mediated liver injury. Prednisolone treatment (30 mg daily) was started and caused rapid normalization of liver enzyme levels. Conclusion: Nilotinib can cause immune-mediated liver injury. The use of corticosteroid can be treatment option in immune-mediated liver injury.
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Affiliation(s)
- Hyun Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Eunpyeong St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea
| | - Pil Soo Sung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea.,The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Eun Sun Jung
- Department of Hospital Pathology, College of Medicine, Eunpyeong St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea
| | - Sungwoo Cho
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Si Hyun Bae
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Eunpyeong St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea.,The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Dong-Wook Kim
- Division of Hematology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea
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