UGT1A1 polymorphism and hyperbilirubinemia in a patient who received sorafenib
Purpose To report a single case of uridine glucuronosyltransferase 1A1 (UGT1A1) polymorphism and hyperbilirubinemia in a patient who received sorafenib. Methods A 63-year-old man with cirrhosis was diagnosed with hepatocellular carcinoma. His cirrhosis was categorized as Child-Pugh A, total bilirubi...
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| creator | Meza-Junco, Judith Chu, Quincy S.-C Christensen, Olaf Rajagopalan, Prabhu Das, Soma Stefanyschyn, Ruslan Sawyer, Michael B |
| description | Purpose To report a single case of uridine glucuronosyltransferase 1A1 (UGT1A1) polymorphism and hyperbilirubinemia in a patient who received sorafenib. Methods A 63-year-old man with cirrhosis was diagnosed with hepatocellular carcinoma. His cirrhosis was categorized as Child-Pugh A, total bilirubin concentration was 24 μmol/L (normal range |
| doi_str_mv | 10.1007/s00280-009-1096-4 |
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Methods A 63-year-old man with cirrhosis was diagnosed with hepatocellular carcinoma. His cirrhosis was categorized as Child-Pugh A, total bilirubin concentration was 24 μmol/L (normal range <20 μmol/L). The patient was enrolled in a phase I trial combination study of cyclophosphamide and doxorubicin combined with sorafenib. Results After a single infusion of doxorubicin and cyclophosphamide and 7 days of sorafenib, he presented with an elevated bilirubin concentration (48 μmol/L). Unconjugated bilirubin was 38 μmol/L and conjugated was 10 μmol/L. The patient was found to have one mutant allele (UGT1A1*28). Conclusions The isolated increase in serum bilirubin levels in our patient was probably due to sorafenib-induced UGT1A1 inhibition that manifested itself due both to the patient having one UGT1A1*28 allele and the presence of underlying liver disease. Bilirubin elevations in patients treated with sorafenib could indicate progression or drug toxicity; hence, these possibilities need to be ruled out. We would suggest that when patients develop hyperbilirubinemia while taking sorafenib for any indication, consideration be given to obtaining a fractionation of bilirubin and consideration of UGT1A1 genotyping in order to exclude a Gilbert's syndrome as possible reason for the hyperbilrubinemia. Further studies are warranted to analyze the impact of sorafenib treatment on unconjugated bilirubin blood levels in patients with Gilbert's syndrome.</description><identifier>ISSN: 0344-5704</identifier><identifier>EISSN: 1432-0843</identifier><identifier>DOI: 10.1007/s00280-009-1096-4</identifier><identifier>PMID: 19672597</identifier><language>eng</language><publisher>Berlin/Heidelberg: Berlin/Heidelberg : Springer-Verlag</publisher><subject><![CDATA[Alleles ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Benzenesulfonates - administration & dosage ; Benzenesulfonates - adverse effects ; Bilirubin ; Blood levels ; Cancer Research ; Carcinoma, Hepatocellular - drug therapy ; Cirrhosis ; Clinical Trials, Phase I as Topic ; Cyclophosphamide ; Cyclophosphamide - administration & dosage ; Doxorubicin ; Doxorubicin - administration & dosage ; Fractionation ; Genotyping ; Gilbert's syndrome ; Glucuronosyltransferase ; Glucuronosyltransferase - antagonists & inhibitors ; Glucuronosyltransferase - genetics ; Hepatocellular carcinoma ; Humans ; Hyperbilirubinemia ; Hyperbilirubinemia - etiology ; Hyperbilirubinemia - genetics ; Impact analysis ; Inhibitor drugs ; Liver cancer ; Liver cirrhosis ; Liver Cirrhosis - complications ; Liver Cirrhosis - physiopathology ; Liver diseases ; Liver Neoplasms - drug therapy ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Mini Review ; Niacinamide - analogs & derivatives ; Oncology ; Patients ; Pharmacology/Toxicology ; Phenylurea Compounds ; Polymorphism ; Polymorphism, Genetic ; Pyridines - administration & dosage ; Pyridines - adverse effects ; Targeted cancer therapy ; Toxicity ; Uridine]]></subject><ispartof>Cancer chemotherapy and pharmacology, 2009-12, Vol.65 (1), p.1-4</ispartof><rights>Springer-Verlag 2009</rights><rights>Springer-Verlag 2009.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c487t-f679cdcd62d1eae42d136b8de466b3d834c39897dee03f403d3a4fc9a69b14f3</citedby><cites>FETCH-LOGICAL-c487t-f679cdcd62d1eae42d136b8de466b3d834c39897dee03f403d3a4fc9a69b14f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00280-009-1096-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00280-009-1096-4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19672597$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Meza-Junco, Judith</creatorcontrib><creatorcontrib>Chu, Quincy S.-C</creatorcontrib><creatorcontrib>Christensen, Olaf</creatorcontrib><creatorcontrib>Rajagopalan, Prabhu</creatorcontrib><creatorcontrib>Das, Soma</creatorcontrib><creatorcontrib>Stefanyschyn, Ruslan</creatorcontrib><creatorcontrib>Sawyer, Michael B</creatorcontrib><title>UGT1A1 polymorphism and hyperbilirubinemia in a patient who received sorafenib</title><title>Cancer chemotherapy and pharmacology</title><addtitle>Cancer Chemother Pharmacol</addtitle><addtitle>Cancer Chemother Pharmacol</addtitle><description>Purpose To report a single case of uridine glucuronosyltransferase 1A1 (UGT1A1) polymorphism and hyperbilirubinemia in a patient who received sorafenib. Methods A 63-year-old man with cirrhosis was diagnosed with hepatocellular carcinoma. His cirrhosis was categorized as Child-Pugh A, total bilirubin concentration was 24 μmol/L (normal range <20 μmol/L). The patient was enrolled in a phase I trial combination study of cyclophosphamide and doxorubicin combined with sorafenib. Results After a single infusion of doxorubicin and cyclophosphamide and 7 days of sorafenib, he presented with an elevated bilirubin concentration (48 μmol/L). Unconjugated bilirubin was 38 μmol/L and conjugated was 10 μmol/L. The patient was found to have one mutant allele (UGT1A1*28). Conclusions The isolated increase in serum bilirubin levels in our patient was probably due to sorafenib-induced UGT1A1 inhibition that manifested itself due both to the patient having one UGT1A1*28 allele and the presence of underlying liver disease. Bilirubin elevations in patients treated with sorafenib could indicate progression or drug toxicity; hence, these possibilities need to be ruled out. We would suggest that when patients develop hyperbilirubinemia while taking sorafenib for any indication, consideration be given to obtaining a fractionation of bilirubin and consideration of UGT1A1 genotyping in order to exclude a Gilbert's syndrome as possible reason for the hyperbilrubinemia. Further studies are warranted to analyze the impact of sorafenib treatment on unconjugated bilirubin blood levels in patients with Gilbert's syndrome.</description><subject>Alleles</subject><subject>Antineoplastic Combined Chemotherapy Protocols - adverse effects</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Benzenesulfonates - administration & dosage</subject><subject>Benzenesulfonates - adverse effects</subject><subject>Bilirubin</subject><subject>Blood levels</subject><subject>Cancer Research</subject><subject>Carcinoma, Hepatocellular - drug therapy</subject><subject>Cirrhosis</subject><subject>Clinical Trials, Phase I as Topic</subject><subject>Cyclophosphamide</subject><subject>Cyclophosphamide - administration & dosage</subject><subject>Doxorubicin</subject><subject>Doxorubicin - administration & dosage</subject><subject>Fractionation</subject><subject>Genotyping</subject><subject>Gilbert's syndrome</subject><subject>Glucuronosyltransferase</subject><subject>Glucuronosyltransferase - antagonists & inhibitors</subject><subject>Glucuronosyltransferase - genetics</subject><subject>Hepatocellular carcinoma</subject><subject>Humans</subject><subject>Hyperbilirubinemia</subject><subject>Hyperbilirubinemia - etiology</subject><subject>Hyperbilirubinemia - genetics</subject><subject>Impact analysis</subject><subject>Inhibitor drugs</subject><subject>Liver cancer</subject><subject>Liver cirrhosis</subject><subject>Liver Cirrhosis - complications</subject><subject>Liver Cirrhosis - physiopathology</subject><subject>Liver diseases</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Mini Review</subject><subject>Niacinamide - analogs & derivatives</subject><subject>Oncology</subject><subject>Patients</subject><subject>Pharmacology/Toxicology</subject><subject>Phenylurea Compounds</subject><subject>Polymorphism</subject><subject>Polymorphism, Genetic</subject><subject>Pyridines - administration & dosage</subject><subject>Pyridines - adverse effects</subject><subject>Targeted cancer therapy</subject><subject>Toxicity</subject><subject>Uridine</subject><issn>0344-5704</issn><issn>1432-0843</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kE1PGzEQhq0KVELaH9BLscp52_HOxLs-IlQ-JASHhrPlXc8So-wHdgLKv-9GG4kTnN7DPO870iPEDwW_FUDxJwHkJWQAJlNgdEZfxEwR5hmUhEdiBkiULQqgE3Ga0jMAkEL8Kk6U0UW-MMVM3D9eL9WFkkO_3rV9HFYhtdJ1Xq52A8cqrEPcVqHjNjgZOunk4DaBu418W_Uycs3hlb1MfXQNd6H6Jo4bt078_ZBzsbz6u7y8ye4erm8vL-6ymspikzW6MLWvvc69Ysc0Buqq9ExaV-hLpBpNaQrPDNgQoEdHTW2cNpWiBufifJodYv-y5bSxz_02duNHm2tDBaGifKR-fUgpXICGEZwLNUF17FOK3NghhtbFnVVg95btZNmOlu3est13fh6Gt1XL_r1x0DoC-QSk8dQ9cXz__Nnq2VRqXG_dUwzJPv7LQSEoXSoyGv8DHdiP3A</recordid><startdate>20091201</startdate><enddate>20091201</enddate><creator>Meza-Junco, Judith</creator><creator>Chu, Quincy S.-C</creator><creator>Christensen, Olaf</creator><creator>Rajagopalan, Prabhu</creator><creator>Das, Soma</creator><creator>Stefanyschyn, Ruslan</creator><creator>Sawyer, Michael B</creator><general>Berlin/Heidelberg : Springer-Verlag</general><general>Springer-Verlag</general><general>Springer Nature B.V</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20091201</creationdate><title>UGT1A1 polymorphism and hyperbilirubinemia in a patient who received sorafenib</title><author>Meza-Junco, Judith ; Chu, Quincy S.-C ; Christensen, Olaf ; Rajagopalan, Prabhu ; Das, Soma ; Stefanyschyn, Ruslan ; Sawyer, Michael B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c487t-f679cdcd62d1eae42d136b8de466b3d834c39897dee03f403d3a4fc9a69b14f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Alleles</topic><topic>Antineoplastic Combined Chemotherapy Protocols - adverse effects</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Benzenesulfonates - administration & dosage</topic><topic>Benzenesulfonates - adverse effects</topic><topic>Bilirubin</topic><topic>Blood levels</topic><topic>Cancer Research</topic><topic>Carcinoma, Hepatocellular - drug therapy</topic><topic>Cirrhosis</topic><topic>Clinical Trials, Phase I as Topic</topic><topic>Cyclophosphamide</topic><topic>Cyclophosphamide - administration & dosage</topic><topic>Doxorubicin</topic><topic>Doxorubicin - administration & dosage</topic><topic>Fractionation</topic><topic>Genotyping</topic><topic>Gilbert's syndrome</topic><topic>Glucuronosyltransferase</topic><topic>Glucuronosyltransferase - antagonists & inhibitors</topic><topic>Glucuronosyltransferase - genetics</topic><topic>Hepatocellular carcinoma</topic><topic>Humans</topic><topic>Hyperbilirubinemia</topic><topic>Hyperbilirubinemia - etiology</topic><topic>Hyperbilirubinemia - genetics</topic><topic>Impact analysis</topic><topic>Inhibitor drugs</topic><topic>Liver cancer</topic><topic>Liver cirrhosis</topic><topic>Liver Cirrhosis - complications</topic><topic>Liver Cirrhosis - physiopathology</topic><topic>Liver diseases</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Mini Review</topic><topic>Niacinamide - analogs & derivatives</topic><topic>Oncology</topic><topic>Patients</topic><topic>Pharmacology/Toxicology</topic><topic>Phenylurea Compounds</topic><topic>Polymorphism</topic><topic>Polymorphism, Genetic</topic><topic>Pyridines - administration & dosage</topic><topic>Pyridines - adverse effects</topic><topic>Targeted cancer therapy</topic><topic>Toxicity</topic><topic>Uridine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Meza-Junco, Judith</creatorcontrib><creatorcontrib>Chu, Quincy S.-C</creatorcontrib><creatorcontrib>Christensen, Olaf</creatorcontrib><creatorcontrib>Rajagopalan, Prabhu</creatorcontrib><creatorcontrib>Das, Soma</creatorcontrib><creatorcontrib>Stefanyschyn, Ruslan</creatorcontrib><creatorcontrib>Sawyer, Michael B</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>Cancer chemotherapy and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Meza-Junco, Judith</au><au>Chu, Quincy S.-C</au><au>Christensen, Olaf</au><au>Rajagopalan, Prabhu</au><au>Das, Soma</au><au>Stefanyschyn, Ruslan</au><au>Sawyer, Michael B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>UGT1A1 polymorphism and hyperbilirubinemia in a patient who received sorafenib</atitle><jtitle>Cancer chemotherapy and pharmacology</jtitle><stitle>Cancer Chemother Pharmacol</stitle><addtitle>Cancer Chemother Pharmacol</addtitle><date>2009-12-01</date><risdate>2009</risdate><volume>65</volume><issue>1</issue><spage>1</spage><epage>4</epage><pages>1-4</pages><issn>0344-5704</issn><eissn>1432-0843</eissn><abstract>Purpose To report a single case of uridine glucuronosyltransferase 1A1 (UGT1A1) polymorphism and hyperbilirubinemia in a patient who received sorafenib. Methods A 63-year-old man with cirrhosis was diagnosed with hepatocellular carcinoma. His cirrhosis was categorized as Child-Pugh A, total bilirubin concentration was 24 μmol/L (normal range <20 μmol/L). The patient was enrolled in a phase I trial combination study of cyclophosphamide and doxorubicin combined with sorafenib. Results After a single infusion of doxorubicin and cyclophosphamide and 7 days of sorafenib, he presented with an elevated bilirubin concentration (48 μmol/L). Unconjugated bilirubin was 38 μmol/L and conjugated was 10 μmol/L. The patient was found to have one mutant allele (UGT1A1*28). Conclusions The isolated increase in serum bilirubin levels in our patient was probably due to sorafenib-induced UGT1A1 inhibition that manifested itself due both to the patient having one UGT1A1*28 allele and the presence of underlying liver disease. Bilirubin elevations in patients treated with sorafenib could indicate progression or drug toxicity; hence, these possibilities need to be ruled out. We would suggest that when patients develop hyperbilirubinemia while taking sorafenib for any indication, consideration be given to obtaining a fractionation of bilirubin and consideration of UGT1A1 genotyping in order to exclude a Gilbert's syndrome as possible reason for the hyperbilrubinemia. Further studies are warranted to analyze the impact of sorafenib treatment on unconjugated bilirubin blood levels in patients with Gilbert's syndrome.</abstract><cop>Berlin/Heidelberg</cop><pub>Berlin/Heidelberg : Springer-Verlag</pub><pmid>19672597</pmid><doi>10.1007/s00280-009-1096-4</doi><tpages>4</tpages></addata></record> |
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| subjects | Alleles Antineoplastic Combined Chemotherapy Protocols - adverse effects Antineoplastic Combined Chemotherapy Protocols - therapeutic use Benzenesulfonates - administration & dosage Benzenesulfonates - adverse effects Bilirubin Blood levels Cancer Research Carcinoma, Hepatocellular - drug therapy Cirrhosis Clinical Trials, Phase I as Topic Cyclophosphamide Cyclophosphamide - administration & dosage Doxorubicin Doxorubicin - administration & dosage Fractionation Genotyping Gilbert's syndrome Glucuronosyltransferase Glucuronosyltransferase - antagonists & inhibitors Glucuronosyltransferase - genetics Hepatocellular carcinoma Humans Hyperbilirubinemia Hyperbilirubinemia - etiology Hyperbilirubinemia - genetics Impact analysis Inhibitor drugs Liver cancer Liver cirrhosis Liver Cirrhosis - complications Liver Cirrhosis - physiopathology Liver diseases Liver Neoplasms - drug therapy Male Medicine Medicine & Public Health Middle Aged Mini Review Niacinamide - analogs & derivatives Oncology Patients Pharmacology/Toxicology Phenylurea Compounds Polymorphism Polymorphism, Genetic Pyridines - administration & dosage Pyridines - adverse effects Targeted cancer therapy Toxicity Uridine |
| title | UGT1A1 polymorphism and hyperbilirubinemia in a patient who received sorafenib |
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