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Viganò M, La Milia M, Grassini MV, Pugliese N, De Giorgio M, Fagiuoli S. Hepatotoxicity of Small Molecule Protein Kinase Inhibitors for Cancer. Cancers (Basel) 2023; 15:cancers15061766. [PMID: 36980652 PMCID: PMC10046041 DOI: 10.3390/cancers15061766] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 03/09/2023] [Accepted: 03/11/2023] [Indexed: 03/17/2023] Open
Abstract
Small molecule protein kinase inhibitors (PKIs) have become an effective strategy for cancer patients. However, hepatotoxicity is a major safety concern of these drugs, since the majority are reported to increase transaminases, and few of them (Idelalisib, Lapatinib, Pazopanib, Pexidartinib, Ponatinib, Regorafenib, Sunitinib) have a boxed label warning. The exact rate of PKI-induced hepatoxicity is not well defined due to the fact that the majority of data arise from pre-registration or registration trials on fairly selected patients, and the post-marketing data are often based only on the most severe described cases, whereas most real practice studies do not include drug-related hepatotoxicity as an end point. Although these side effects are usually reversible by dose adjustment or therapy suspension, or by switching to an alternative PKI, and fatality is uncommon, all patients undergoing PKIs should be carefully pre-evaluated and monitored. The management of this complication requires an individually tailored reappraisal of the risk/benefit ratio, especially in patients who are responding to therapy. This review reports the currently available data on the risk and management of hepatotoxicity of all the approved PKIs.
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Affiliation(s)
- Mauro Viganò
- Gastroenterology Hepatology and Transplantation Unit, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy
- Correspondence: ; Tel.: +39-035-2674259; Fax: +39-035-2674964
| | - Marta La Milia
- Gastroenterology Hepatology and Transplantation Unit, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy
| | - Maria Vittoria Grassini
- Gastroenterology Hepatology and Transplantation Unit, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy
- Section of Gastroenterology & Hepatology, Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy
| | - Nicola Pugliese
- Department of Gastroenterology, Division of Internal Medicine and Hepatology, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Massimo De Giorgio
- Gastroenterology Hepatology and Transplantation Unit, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy
| | - Stefano Fagiuoli
- Gastroenterology Hepatology and Transplantation Unit, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy
- Gastroenterology, Department of Medicine, University of Milan Bicocca, 20126 Milan, Italy
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Peng L, Xiao K, Cui J, Ye XH, Zhang YC, Mao L, Selvaggi G, Yen J, Stebbing J. Successful Treatment with Ensartinib After Alectinib-induced Hyperbilirubinemia in ALK-Positive NSCLC. Onco Targets Ther 2021; 14:3409-3415. [PMID: 34079286 PMCID: PMC8164872 DOI: 10.2147/ott.s310756] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Accepted: 04/28/2021] [Indexed: 12/15/2022] Open
Abstract
Background Alectinib is approved for the treatment of advanced non-small-cell lung cancer (NSCLC) harboring ALK rearrangements. Although generally well tolerated, alectinib can cause serious or life-threatening side effects. Case Presentation Here, we report a case of a patient with NSCLC with an EML4-ALK fusion and was treated with alectinib but who developed grade 4 hyperbilirubinemia after five months on therapy. Alectinib was discontinued, and an artificial liver support system (ALSS) was used with an impressive decline in bilirubin levels. After two months drug-free, the patient experienced disease progression. Ensartinib was initiated as second-line treatment with a best response of stable disease after three months of therapy with no evidence of hyperbilirubinemia. Conclusion This is the first report of ensartinib treatment after alectinib-induced hyperbilirubinemia which was successfully relieved by ALSS treatment and targeted drug cessation.
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Affiliation(s)
- Ling Peng
- Department of Pulmonary and Critical Care Medicine, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang Province, People's Republic of China
| | - Kui Xiao
- Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, People's Republic of China
| | - Jian Cui
- Shanghai BioGenius Bioinformatics Institute, Shanghai, People's Republic of China
| | - Xiang-Hua Ye
- Department of Radiotherapy, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China
| | - Yong-Chang Zhang
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, Hunan, People's Republic of China
| | - Li Mao
- Betta Pharmaceuticals, Hangzhou, People's Republic of China
| | | | | | - Justin Stebbing
- Division of Cancer, Department of Surgery and Cancer, Imperial College London, London, UK
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Houron C, Danielou M, Mir O, Fromenty B, Perlemuter G, Voican CS. Multikinase inhibitor-induced liver injury in patients with cancer: A review for clinicians. Crit Rev Oncol Hematol 2020; 157:103127. [PMID: 33161366 DOI: 10.1016/j.critrevonc.2020.103127] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 09/29/2020] [Accepted: 10/05/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Multikinase inhibitors (MKI) are targeted molecular agents that have revolutionized cancer management. However, there is a paucity of data concerning MKI-related liver injury risk and clinical guidelines for the management of liver toxicity in patients receiving MKI for cancer are scarce. DESIGN We conducted a PubMed search of articles in English published from January 2000 to December 2018 related to hepatotoxicity of the 29 FDA-approved MKIs at doses used in clinical practice. The search terms were the international non-proprietary name of each agent cross-referenced with «hepatotoxicity», «hepatitis», «hepatic adverse event», or «liver failure», and «phase II clinical trial», «phase III clinical trial», or «case report». RESULTS Following this search, 140 relevant studies and 99 case reports were considered. Although asymptomatic elevation of aminotransferase levels has been frequently observed in MKI clinical trials, clinically significant hepatotoxicity is a rare event. In most cases, the interval between treatment initiation and the onset of liver injury is between one week and two months. Liver toxicity is often hepatocellular and less frequently mixed. Life-threatening MKI-induced hepatic injury has been described, involving fulminant liver failure or death. Starting from existing data, a description of MKI-related liver events, grading of hepatotoxicity risk, and recommendations for management are also given for various MKI molecules. CONCLUSION All MKIs can potentially cause liver injury, which is sometimes irreversible. As there is still no strategy available to prevent MKI-related hepatotoxicity, early detection remains crucial. The surveillance of liver function during treatment may help in the early detection of hepatotoxicity. Furthermore, the exclusion of potential causes of hepatic injury is essential to avoid unnecessary MKI withdrawal.
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Affiliation(s)
- Camille Houron
- Faculté de Médecine Paris-Saclay, Université Paris-Saclay, F-94276, Le Kremlin-Bicêtre, France; INSERM U996, DHU Hepatinov, Labex LERMIT, F-92140, Clamart, France
| | - Marie Danielou
- Faculté de Médecine Paris-Saclay, Université Paris-Saclay, F-94276, Le Kremlin-Bicêtre, France; Service d'Hépato-Gastroentérologie et Nutrition, Hôpital Antoine-Béclère, AP-HP, Université Paris-Saclay, F-92140, Clamart, France
| | - Olivier Mir
- Gustave Roussy Cancer Campus, Department of Ambulatory Care, F-94805, Villejuif, France
| | - Bernard Fromenty
- INSERM, INRAE, Univ Rennes, Institut NUMECAN (Nutrition Metabolisms and Cancer), UMR_A 1341, UMR_S 1241, F-35000, Rennes, France
| | - Gabriel Perlemuter
- Faculté de Médecine Paris-Saclay, Université Paris-Saclay, F-94276, Le Kremlin-Bicêtre, France; INSERM U996, DHU Hepatinov, Labex LERMIT, F-92140, Clamart, France; Service d'Hépato-Gastroentérologie et Nutrition, Hôpital Antoine-Béclère, AP-HP, Université Paris-Saclay, F-92140, Clamart, France.
| | - Cosmin Sebastian Voican
- Faculté de Médecine Paris-Saclay, Université Paris-Saclay, F-94276, Le Kremlin-Bicêtre, France; INSERM U996, DHU Hepatinov, Labex LERMIT, F-92140, Clamart, France; Service d'Hépato-Gastroentérologie et Nutrition, Hôpital Antoine-Béclère, AP-HP, Université Paris-Saclay, F-92140, Clamart, France
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Successful Treatment of Crizotinib-Induced Fulminant Liver Failure: A Case Report and Review of Literature. Case Reports Hepatol 2020; 2020:8247960. [PMID: 32231818 PMCID: PMC7085870 DOI: 10.1155/2020/8247960] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Accepted: 02/14/2020] [Indexed: 01/05/2023] Open
Abstract
Crizotinib is a first-line tyrosine kinase inhibitor used for the treatment of metastatic lung cancer. Crizotinib-induced hepatotoxicity is a rare event. We report a case of a 46-year-old female with a history of metastatic lung cancer who presented with acute liver failure after being on crizotinib for two months. The medication was discontinued, and she was treated with N-acetylcysteine for seven days. Her liver function tests returned to normal limits after 26 days after admission. The precise mechanism and risk factors of crizotinib-induced hepatotoxicity remain unknown. Physicians should be aware of the potentially lethal side effect caused by crizotinib.
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Song SH, Ryu JW, Jwa HY, Ha CW, Kim H, Jo JM, Han SH. ALK-positive lung cancer diagnosed with abdominal lymph nodes in a patient receiving hemodialysis. Thorac Cancer 2019; 10:2188-2191. [PMID: 31588629 PMCID: PMC6825909 DOI: 10.1111/1759-7714.13205] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Revised: 09/08/2019] [Accepted: 09/08/2019] [Indexed: 11/28/2022] Open
Abstract
There is little consensus in the literature about the administration of crizotinib in patients with end-stage renal disease undergoing hemodialysis. A 69-year-old male patient, who was receiving regular hemodialysis due to end-stage renal disease, visited the hospital with symptoms of repeated abdominal pain. There was no suspicious finding of cancer within the thorax. After biopsy, the abdominal lymph nodes were identified as adenocarcinoma originating from the lung following computed tomography (CT) scan, and ALK rearrangement was confirmed. The patient achieved a partial response following the administration of crizotinib, although treatment was discontinued because of unknown cholestasis. Overall survival was eight months. Although crizotinib has clear efficacy in patients with ALK-positive lung cancer with end-stage renal disease, the optimal dose of crizotinib should be identified in patients receiving regular hemodialysis.
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Affiliation(s)
- Sung H Song
- Department of Internal Medicine, Cheju Halla General Hospital, Jeju, Republic of Korea
| | - Ji W Ryu
- Department of Internal Medicine, Cheju Halla General Hospital, Jeju, Republic of Korea
| | - Hye Y Jwa
- Department of Internal Medicine, Cheju Halla General Hospital, Jeju, Republic of Korea
| | - Chang W Ha
- Department of Pathology, Cheju Halla General Hospital, Jeju, Republic of Korea
| | - Hyun Kim
- Department of Radiology, Cheju Halla General Hospital, Jeju, Republic of Korea
| | - Jae M Jo
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Republic of Korea
| | - Sang H Han
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Republic of Korea
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Ota T, Masuda N, Matsui K, Yamada T, Tanaka N, Fujimoto S, Fukuoka M. Successful Desensitization with Crizotinib after Crizotinib-induced Liver Injury in ROS1-rearranged Lung Adenocarcinoma. Intern Med 2019; 58:2651-2655. [PMID: 31178493 PMCID: PMC6794186 DOI: 10.2169/internalmedicine.2554-18] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Crizotinib has been approved for patients with advanced lung adenocarcinoma harboring rearrangements of the c-ROS-1 (ROS1) and anaplastic lymphoma kinase (ALK) genes. We report a patient with ROS1-rearranged lung adenocarcinoma who developed a crizotinib-induced mixed/cholestatic type of liver injury. The patient discontinued crizotinib after 34 days due to liver toxicity. Twenty-four days later, when transaminases and C reactive protein (CRP) were normalized, crizotinib was resumed using an oral desensitization method. The patient was successfully treated for manageable recurrence of liver injury and has been able to continue the treatment.
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Affiliation(s)
- Takayo Ota
- Department of Medical Oncology, Izumi City General Hospital, Japan
| | - Noriyuki Masuda
- Department of Medical Oncology, Izumi City General Hospital, Japan
| | - Kaoru Matsui
- Department of Medical Oncology, Izumi City General Hospital, Japan
| | - Takao Yamada
- Department of Gastroenterology, Izumi City General Hospital, Japan
| | - Noriko Tanaka
- Department of Radiology, Izumi City General Hospital, Japan
| | | | - Masahiro Fukuoka
- Department of Medical Oncology, Izumi City General Hospital, Japan
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D’Antonio F, De Sanctis R, Bolengo I, Destro A, Rahal D, De Vincenzo F, Santoro A. Pulmonary sarcomatoid carcinoma presenting both ALK rearrangement and PD-L1 high positivity: A case report on the therapeutic regimen. Medicine (Baltimore) 2019; 98:e16754. [PMID: 31393391 PMCID: PMC6708868 DOI: 10.1097/md.0000000000016754] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
RATIONALE Pulmonary sarcomatoid carcinoma (PSC) represents <1% of all lung cancers and is characterized by a very poor prognosis. The optimal therapeutic regimen remains unclear. We describe a rare case of PSC with both anaplastic lymphoma kinase (ALK)-arranged and high levels of programmed death ligand 1 (PD-L1) expression. PATIENT CONCERNS A 46-year-old woman, nonsmoker, came to our attention due to uncontrolled pain in the lower left limb. DIAGNOSIS PSC with both ALK rearrangement and high levels of PD-L1 expression. INTERVENTIONS The patient started first-line systemic treatment with pembrolizumab reporting stable disease; at progression, she received second-line treatment with crizotinib. The treatment was not well-tolerated, and the patient then underwent 5 cycles of ceritinib treatment. OUTCOMES The patient showed a partial response to targeted therapy. At progression, brigatinib was initiated, but the patients reported liver progression soon after the initiation of this therapy. LESSONS Molecular-driven investigation is necessary in PSC for treatment selection.
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Affiliation(s)
| | - Rita De Sanctis
- Medical Oncology and Hematology Unit, Humanitas Cancer Center
| | | | - Annarita Destro
- Pathology Department, Humanitas Clinical and Research Center – IRCCS, Rozzano
| | - Daoud Rahal
- Pathology Department, Humanitas Clinical and Research Center – IRCCS, Rozzano
| | | | - Armando Santoro
- Medical Oncology and Hematology Unit, Humanitas Cancer Center
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
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Zhang Y, Xu YY, Chen Y, Li JN, Wang Y. Crizotinib-induced acute fatal liver failure in an Asian ALK-positive lung adenocarcinoma patient with liver metastasis: A case report. World J Clin Cases 2019; 7:1080-1086. [PMID: 31123682 PMCID: PMC6511925 DOI: 10.12998/wjcc.v7.i9.1080] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2018] [Revised: 02/25/2019] [Accepted: 03/09/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Crizotinib-induce hepatotoxicity is rare and non-specific, and severe hepatotoxicity can develop into fatal liver failure. Herein, we report a case of fatal crizotinib-induced liver failure in a 37-year-old Asian patient.
CASE SUMMARY The patient complained of dyspnea and upper abdominal pain for a week in August 2017. He was diagnosed with anaplastic lymphoma kinase-rearranged lung adenocarcinoma combined with multiple distant metastases. Crizotinib was initiated as a first-line treatment at a dosage of 250 mg twice daily. No adverse effects were seen until day 46. On day 55, he was admitted to the hospital with elevated liver enzymes aspartate aminotransferase (AST) (402 IU/L), alanine aminotransferase (ALT) (215 IU/L) and total bilirubin (145 μmol/L) and was diagnosed with crizotinib-induced fulminant liver failure. Despite crizotinib discontinuation and intensive supportive therapy, the level of AST (1075 IU/L), ALT (240 IU/L) and total bilirubin (233 μmol/L) continued to rapidly increase, and he died on day 60.
CONCLUSION Physicians should be aware of the potential fatal adverse effects of crizotinib.
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Affiliation(s)
- Ying Zhang
- Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
| | - Yan-Yan Xu
- Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
| | - Yi Chen
- Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
| | - Jin-Na Li
- Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
| | - Ying Wang
- Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
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Brivio E, Zwaan CM. ALK inhibition in two emblematic cases of pediatric inflammatory myofibroblastic tumor: Efficacy and side effects. Pediatr Blood Cancer 2019; 66:e27645. [PMID: 30697903 DOI: 10.1002/pbc.27645] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Revised: 01/07/2019] [Accepted: 01/18/2019] [Indexed: 12/13/2022]
Abstract
There is an increasing interest for anaplastic lymphoma kinase (ALK) inhibitors in pediatric oncology for specific entities such as ALK-driven inflammatory myofibroblastic tumor (IMT). IMT treatment can be challenging due to localization of the tumor and in rare cases of metastasis. When standard surgical treatment is not feasible, ALK inhibitors may play an important role, as recently reported for the first-generation ALK inhibitors (crizotinib). However, data on the second-generation ALK inhibitors are limited. We report two emblematic cases of IMT in pediatric patients, treated with the second-generation ALK inhibitor ceritinib in the context of a clinical trial (NCT01742286).
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Affiliation(s)
- Erica Brivio
- Prinses Maxima Centrum, Center for Pediatric Oncology, Utrecht, the Netherlands
| | - C Michel Zwaan
- Prinses Maxima Centrum, Center for Pediatric Oncology, Utrecht, the Netherlands.,Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands
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Yasuda Y, Nishikawa Y, Sakamori Y, Terao M, Hashimoto K, Funazo T, Nomizo T, Tsuji T, Yoshida H, Nagai H, Ozasa H, Hirai T, Kim YH. Successful oral desensitization with crizotinib after crizotinib-induced hepatitis in an anaplastic lymphoma kinase-rearranged non-small-cell lung cancer patient: A case report. Mol Clin Oncol 2017; 7:295-297. [PMID: 28781805 DOI: 10.3892/mco.2017.1310] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Accepted: 04/13/2017] [Indexed: 01/12/2023] Open
Abstract
Crizotinib is one of the molecularly-targeted agents targeted against anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC). Although its effects appear to be promising, crizotinib may cause adverse effects in patients with ALK-rearranged NSCLC. Hepatic laboratory abnormalities are frequently observed with crizotinib and treatment discontinuation is occasionally required. We herein report the case of a 51-year-old woman diagnosed with relapsed ALK-rearranged NSCLC, who received crizotinib as second-line systemic chemotherapy. After 17 days of crizotinib therapy, the patient developed grade >3 hepatotoxicity. Treatment discontinuation improved the laboratory abnormalities and fifth-line oral desensitization with crizotinib achieved successful response without hepatotoxicity. Therefore, oral desensitization with crizotinib may be a viable option following crizotinib-induced hepatitis.
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Affiliation(s)
- Yuto Yasuda
- Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
| | - Yasuyo Nishikawa
- Department of Surgery, Gastrointestinal Center, Kyoto-Katsura Hospital, Kyoto 615-8256, Japan
| | - Yuichi Sakamori
- Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
| | - Makoto Terao
- Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto 606-8507, Japan
| | - Kentaro Hashimoto
- Department of Respiratory Medicine, Shiga Medical Center for Adults, Moriyama, Shiga 524-0022, Japan
| | - Tomoko Funazo
- Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
| | - Takashi Nomizo
- Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
| | - Takahiro Tsuji
- Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
| | - Hironori Yoshida
- Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
| | - Hiroki Nagai
- Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
| | - Hiroaki Ozasa
- Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
| | - Toyohiro Hirai
- Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
| | - Young Hak Kim
- Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
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Qian M, Zhu B, Wang X, Liebman M. Drug resistance in ALK-positiveNon-small cell lungcancer patients. Semin Cell Dev Biol 2017; 64:150-157. [DOI: 10.1016/j.semcdb.2016.09.016] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Accepted: 09/28/2016] [Indexed: 02/07/2023]
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