• Je něco špatně v tomto záznamu ?

Severe tyrosine-kinase inhibitor induced liver injury in metastatic renal cell carcinoma patients: two case reports assessed for causality using the updated RUCAM and review of the literature

H. Studentova, J. Volakova, M. Spisarova, A. Zemankova, K. Aiglova, T. Szotkowski, B. Melichar

. 2022 ; 22 (1) : 49. [pub] 20220205

Jazyk angličtina Země Velká Británie

Typ dokumentu kazuistiky, časopisecké články, přehledy

Perzistentní odkaz   https://www.medvik.cz/link/bmc22011054

Grantová podpora
17-16614S Grantová Agentura České Republiky

BACKGROUND: Sunitinib and pazopanib are both oral small molecule multityrosine kinase inhibitors (MTKI) used in the treatment of renal cell carcinoma (RCC). Hepatotoxicity or "liver injury" is the most important adverse effect of pazopanib administration, but little is known about the underlying mechanism. Liver injury may also occur in patients treated with sunitinib, but severe toxicity is extremely rare. Herein we report two new cases of severe liver injury induced by MTKI. Both cases are unique and exceptional. We assessed both cases for drug-induced liver injury (DILI) using the updated score Roussel Uclaf causality assessment method (RUCAM). The literature on potential pathogenic mechanisms and precautionary measures is reviewed. CASE PRESENTATION: A case of a metastatic RCC (mRCC) patient treated with pazopanib who had manifestation of severe liver injury is presented. These manifestations consisted of grade 4 alanine aminotransferase (ALT) increase and grade 4 hyperbilirubinemia. Alternate causes of acute or chronic liver disease were excluded. The patient gradually recovered from the liver injury and refused any further therapy for mRCC. The patient was diagnosed with acute myeloid leukemia (AML) two years later and eventually succumbed to the disease. The second case describes a mRCC patient treated with sunitinib for 3,5 years and fatal liver failure after 2 weeks of clarithromycin co-medication for acute bronchitis. CONCLUSIONS: Liver injury has been commonly observed in TKI-treated patients with unpredictable course. Management requires regular routine liver enzyme-monitoring and the collaboration of medical oncologist and hepatologist. There is an unmet medical need for a risk stratification and definition of predictive biomarkers to identify potential genetic polymorphisms or other factors associated with TKI-induced liver injury. Any potential unrecommended concomitant therapy has to be avoided.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc22011054
003      
CZ-PrNML
005      
20220506130332.0
007      
ta
008      
220425s2022 xxk f 000 0|eng||
009      
AR
024    7_
$a 10.1186/s12876-022-02121-3 $2 doi
035    __
$a (PubMed)35123392
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxk
100    1_
$a Studentova, Hana $u Department of Oncology, Palacký University Medical School and Teaching Hospital, Olomouc, Czech Republic. hanastudentova@email.cz $1 https://orcid.org/0000000321059258
245    10
$a Severe tyrosine-kinase inhibitor induced liver injury in metastatic renal cell carcinoma patients: two case reports assessed for causality using the updated RUCAM and review of the literature / $c H. Studentova, J. Volakova, M. Spisarova, A. Zemankova, K. Aiglova, T. Szotkowski, B. Melichar
520    9_
$a BACKGROUND: Sunitinib and pazopanib are both oral small molecule multityrosine kinase inhibitors (MTKI) used in the treatment of renal cell carcinoma (RCC). Hepatotoxicity or "liver injury" is the most important adverse effect of pazopanib administration, but little is known about the underlying mechanism. Liver injury may also occur in patients treated with sunitinib, but severe toxicity is extremely rare. Herein we report two new cases of severe liver injury induced by MTKI. Both cases are unique and exceptional. We assessed both cases for drug-induced liver injury (DILI) using the updated score Roussel Uclaf causality assessment method (RUCAM). The literature on potential pathogenic mechanisms and precautionary measures is reviewed. CASE PRESENTATION: A case of a metastatic RCC (mRCC) patient treated with pazopanib who had manifestation of severe liver injury is presented. These manifestations consisted of grade 4 alanine aminotransferase (ALT) increase and grade 4 hyperbilirubinemia. Alternate causes of acute or chronic liver disease were excluded. The patient gradually recovered from the liver injury and refused any further therapy for mRCC. The patient was diagnosed with acute myeloid leukemia (AML) two years later and eventually succumbed to the disease. The second case describes a mRCC patient treated with sunitinib for 3,5 years and fatal liver failure after 2 weeks of clarithromycin co-medication for acute bronchitis. CONCLUSIONS: Liver injury has been commonly observed in TKI-treated patients with unpredictable course. Management requires regular routine liver enzyme-monitoring and the collaboration of medical oncologist and hepatologist. There is an unmet medical need for a risk stratification and definition of predictive biomarkers to identify potential genetic polymorphisms or other factors associated with TKI-induced liver injury. Any potential unrecommended concomitant therapy has to be avoided.
650    12
$a karcinom z renálních buněk $x farmakoterapie $7 D002292
650    12
$a lékové postižení jater $x etiologie $7 D056486
650    12
$a chronické poškození jater způsobené chemickými látkami $7 D056487
650    _2
$a lidé $7 D006801
650    12
$a nádory ledvin $x farmakoterapie $7 D007680
650    _2
$a tyrosin $7 D014443
655    _2
$a kazuistiky $7 D002363
655    _2
$a časopisecké články $7 D016428
655    _2
$a přehledy $7 D016454
700    1_
$a Volakova, Jindriska $u Deparment of Clinical Pharmacology, Palacký University Medical School and Teaching Hospital, Olomouc, Czech Republic
700    1_
$a Spisarova, Martina $u Department of Oncology, Palacký University Medical School and Teaching Hospital, Olomouc, Czech Republic
700    1_
$a Zemankova, Anezka $u Department of Oncology, Palacký University Medical School and Teaching Hospital, Olomouc, Czech Republic
700    1_
$a Aiglova, Kvetoslava $u Second Department of Internal Medicine, Palacký University Medical School and Teaching Hospital, Olomouc, Czech Republic
700    1_
$a Szotkowski, Tomas $u Department of Hemato-Oncology, Palacký University Medical School and Teaching Hospital, Olomouc, Czech Republic
700    1_
$a Melichar, Bohuslav $u Department of Oncology, Palacký University Medical School and Teaching Hospital, Olomouc, Czech Republic $u Institute of Molecular and Translational Medicine, Palacký University Medical School and Teaching Hospital, Olomouc, Czech Republic
773    0_
$w MED00006914 $t BMC gastroenterology $x 1471-230X $g Roč. 22, č. 1 (2022), s. 49
856    41
$u https://pubmed.ncbi.nlm.nih.gov/35123392 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20220425 $b ABA008
991    __
$a 20220506130324 $b ABA008
999    __
$a ok $b bmc $g 1788912 $s 1162252
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2022 $b 22 $c 1 $d 49 $e 20220205 $i 1471-230X $m BMC gastroenterology $n BMC Gastroenterol $x MED00006914
GRA    __
$a 17-16614S $p Grantová Agentura České Republiky
LZP    __
$a Pubmed-20220425

Najít záznam

Citační ukazatele

Možnosti archivace