Pharmacogenetic impact of UGT1A1 polymorphisms on pulmonary neuroendocrine tumours treated with metronomic irinotecan-based chemotherapy in Chinese populations
Abstract Objectives To evaluate the effects of UGT1A1*6 and UGT1A1*28 polymorphisms on the safety and efficacy of metronomic irinotecan-based chemotherapy (IBC) in Chinese patients with pulmonary neuroendocrine tumours (PNTs). Methods Sixty-eight PNT patients who received metronomic IBC were observe...
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| Veröffentlicht in: | Journal of pharmacy and pharmacology 2020-11, Vol.72 (11), p.1528-1535 |
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| creator | Ma, Xu Han, Sen Liu, Ying Liu, Jing-Tao Fang, Jian Zhang, Yan-Hua |
| description | Abstract
Objectives
To evaluate the effects of UGT1A1*6 and UGT1A1*28 polymorphisms on the safety and efficacy of metronomic irinotecan-based chemotherapy (IBC) in Chinese patients with pulmonary neuroendocrine tumours (PNTs).
Methods
Sixty-eight PNT patients who received metronomic IBC were observed. The quantitative fluorescent polymerase chain reaction was used to detect UGT1A1*6 and UGT1A1*28 polymorphisms. The follow-up data were collected to investigate the relationship between different genotypes and adverse drug reactions. The clinical outcomes of metronomic IBC were also evaluated.
Key findings
In the genotype–toxicity association analysis, patients with homozygous UGT1A1*6 had the highest incidence of grade 3-4 diarrhoea (P = 0.010). Compared to other groups, patients with the haplotype of UGT1A1*28 showed a trend towards an increased incidence of grade 4 neutropaenia (P = 0.047). A higher incidence of grade 3–4 leucopaenia was found in groups with UGT1A1*1/*28 (P = 0.023) and UGT1A1*28/*28 (P = 0.022). Grade 1 total bilirubin elevation was associated with the homozygous UGT1A1*6 mutation (P = 0.027) or any UGT1A1*6 variants (P = 0.047). However, neither UGTA1A*28 nor UGT1A1*6 showed any significant association with tumour response or clinical outcomes.
Conclusions
The impact of UGT1A1 polymorphisms varies in different irinotecan-based chemotherapies. UGT1A1*6 and UGTA1A*28 were useful for the prediction of irinotecan-related severe toxicity in Chinese PNT patients treated with metronomic IBC. |
| doi_str_mv | 10.1111/jphp.13333 |
| format | Article |
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Objectives
To evaluate the effects of UGT1A1*6 and UGT1A1*28 polymorphisms on the safety and efficacy of metronomic irinotecan-based chemotherapy (IBC) in Chinese patients with pulmonary neuroendocrine tumours (PNTs).
Methods
Sixty-eight PNT patients who received metronomic IBC were observed. The quantitative fluorescent polymerase chain reaction was used to detect UGT1A1*6 and UGT1A1*28 polymorphisms. The follow-up data were collected to investigate the relationship between different genotypes and adverse drug reactions. The clinical outcomes of metronomic IBC were also evaluated.
Key findings
In the genotype–toxicity association analysis, patients with homozygous UGT1A1*6 had the highest incidence of grade 3-4 diarrhoea (P = 0.010). Compared to other groups, patients with the haplotype of UGT1A1*28 showed a trend towards an increased incidence of grade 4 neutropaenia (P = 0.047). A higher incidence of grade 3–4 leucopaenia was found in groups with UGT1A1*1/*28 (P = 0.023) and UGT1A1*28/*28 (P = 0.022). Grade 1 total bilirubin elevation was associated with the homozygous UGT1A1*6 mutation (P = 0.027) or any UGT1A1*6 variants (P = 0.047). However, neither UGTA1A*28 nor UGT1A1*6 showed any significant association with tumour response or clinical outcomes.
Conclusions
The impact of UGT1A1 polymorphisms varies in different irinotecan-based chemotherapies. UGT1A1*6 and UGTA1A*28 were useful for the prediction of irinotecan-related severe toxicity in Chinese PNT patients treated with metronomic IBC.</description><identifier>ISSN: 0022-3573</identifier><identifier>EISSN: 2042-7158</identifier><identifier>DOI: 10.1111/jphp.13333</identifier><language>eng</language><publisher>Bognor Regis: Oxford University Press</publisher><subject>Association analysis ; Bilirubin ; Chemotherapy ; Clinical outcomes ; Diarrhea ; Haplotypes ; Irinotecan ; Neuroendocrine tumors ; Polymerase chain reaction ; pulmonary neuroendocrine tumour ; single nucleotide polymorphisms ; Toxicity ; UGT1A128 ; UGT1A16</subject><ispartof>Journal of pharmacy and pharmacology, 2020-11, Vol.72 (11), p.1528-1535</ispartof><rights>2020 Royal Pharmaceutical Society 2020</rights><rights>2020 Royal Pharmaceutical Society</rights><rights>Copyright © 2020 Royal Pharmaceutical Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4003-a7d65a635b5d5fb2d1682f66cecaa8dd63f6295c07ee39801ff24a9e6ff6f70f3</citedby><cites>FETCH-LOGICAL-c4003-a7d65a635b5d5fb2d1682f66cecaa8dd63f6295c07ee39801ff24a9e6ff6f70f3</cites><orcidid>0000-0003-1649-2284 ; 0000-0003-4344-574X ; 0000-0002-5891-5225 ; 0000-0002-3340-5958 ; 0000-0002-2752-7270 ; 0000-0003-3697-4563</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjphp.13333$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjphp.13333$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids></links><search><creatorcontrib>Ma, Xu</creatorcontrib><creatorcontrib>Han, Sen</creatorcontrib><creatorcontrib>Liu, Ying</creatorcontrib><creatorcontrib>Liu, Jing-Tao</creatorcontrib><creatorcontrib>Fang, Jian</creatorcontrib><creatorcontrib>Zhang, Yan-Hua</creatorcontrib><title>Pharmacogenetic impact of UGT1A1 polymorphisms on pulmonary neuroendocrine tumours treated with metronomic irinotecan-based chemotherapy in Chinese populations</title><title>Journal of pharmacy and pharmacology</title><description>Abstract
Objectives
To evaluate the effects of UGT1A1*6 and UGT1A1*28 polymorphisms on the safety and efficacy of metronomic irinotecan-based chemotherapy (IBC) in Chinese patients with pulmonary neuroendocrine tumours (PNTs).
Methods
Sixty-eight PNT patients who received metronomic IBC were observed. The quantitative fluorescent polymerase chain reaction was used to detect UGT1A1*6 and UGT1A1*28 polymorphisms. The follow-up data were collected to investigate the relationship between different genotypes and adverse drug reactions. The clinical outcomes of metronomic IBC were also evaluated.
Key findings
In the genotype–toxicity association analysis, patients with homozygous UGT1A1*6 had the highest incidence of grade 3-4 diarrhoea (P = 0.010). Compared to other groups, patients with the haplotype of UGT1A1*28 showed a trend towards an increased incidence of grade 4 neutropaenia (P = 0.047). A higher incidence of grade 3–4 leucopaenia was found in groups with UGT1A1*1/*28 (P = 0.023) and UGT1A1*28/*28 (P = 0.022). Grade 1 total bilirubin elevation was associated with the homozygous UGT1A1*6 mutation (P = 0.027) or any UGT1A1*6 variants (P = 0.047). However, neither UGTA1A*28 nor UGT1A1*6 showed any significant association with tumour response or clinical outcomes.
Conclusions
The impact of UGT1A1 polymorphisms varies in different irinotecan-based chemotherapies. UGT1A1*6 and UGTA1A*28 were useful for the prediction of irinotecan-related severe toxicity in Chinese PNT patients treated with metronomic IBC.</description><subject>Association analysis</subject><subject>Bilirubin</subject><subject>Chemotherapy</subject><subject>Clinical outcomes</subject><subject>Diarrhea</subject><subject>Haplotypes</subject><subject>Irinotecan</subject><subject>Neuroendocrine tumors</subject><subject>Polymerase chain reaction</subject><subject>pulmonary neuroendocrine tumour</subject><subject>single nucleotide polymorphisms</subject><subject>Toxicity</subject><subject>UGT1A128</subject><subject>UGT1A16</subject><issn>0022-3573</issn><issn>2042-7158</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kUFP3DAQha2KSiy0F36BJdQLUqjtJE72iFYFWiF1D3COvM648WrtMbYjtL-mfxUvC1fmMpfvvaeZR8gFZ9e8zM9tmMI1r8t8IQvBGlF1vO1PyIIxIaq67epTcpbSljHWSSkX5P96UtEpjf_AQ7aaWheUzhQNfbp75DecBtztHcYw2eQSRU_DvHPoVdxTD3NE8CPqaD3QPDucY6I5gsow0hebJ-ogR_ToDtaFwgxa-WqjUgH0BA7zBFGFPbWerqZik6BElgyVLfr0jXw1apfg-_s-J0-3vx5X99XD37vfq5uHSjeM1ZXqRtkqWbebdmzNRoxc9sJIqUua6sdR1kaKZatZB1Ave8aNEY1agjRGmo6Z-pxcHn1DxOcZUh625RZfIgfRNH3LZdOzQl0dKR0xpQhmCNG68oqBs-FQwHAoYHgroMD8CL_YHew_IYc_6_v1h-bHUYNz-Mz7FdA1mfY</recordid><startdate>202011</startdate><enddate>202011</enddate><creator>Ma, Xu</creator><creator>Han, Sen</creator><creator>Liu, Ying</creator><creator>Liu, Jing-Tao</creator><creator>Fang, Jian</creator><creator>Zhang, Yan-Hua</creator><general>Oxford University Press</general><general>Wiley Subscription Services, Inc</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TK</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><orcidid>https://orcid.org/0000-0003-1649-2284</orcidid><orcidid>https://orcid.org/0000-0003-4344-574X</orcidid><orcidid>https://orcid.org/0000-0002-5891-5225</orcidid><orcidid>https://orcid.org/0000-0002-3340-5958</orcidid><orcidid>https://orcid.org/0000-0002-2752-7270</orcidid><orcidid>https://orcid.org/0000-0003-3697-4563</orcidid></search><sort><creationdate>202011</creationdate><title>Pharmacogenetic impact of UGT1A1 polymorphisms on pulmonary neuroendocrine tumours treated with metronomic irinotecan-based chemotherapy in Chinese populations</title><author>Ma, Xu ; Han, Sen ; Liu, Ying ; Liu, Jing-Tao ; Fang, Jian ; Zhang, Yan-Hua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4003-a7d65a635b5d5fb2d1682f66cecaa8dd63f6295c07ee39801ff24a9e6ff6f70f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Association analysis</topic><topic>Bilirubin</topic><topic>Chemotherapy</topic><topic>Clinical outcomes</topic><topic>Diarrhea</topic><topic>Haplotypes</topic><topic>Irinotecan</topic><topic>Neuroendocrine tumors</topic><topic>Polymerase chain reaction</topic><topic>pulmonary neuroendocrine tumour</topic><topic>single nucleotide polymorphisms</topic><topic>Toxicity</topic><topic>UGT1A128</topic><topic>UGT1A16</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ma, Xu</creatorcontrib><creatorcontrib>Han, Sen</creatorcontrib><creatorcontrib>Liu, Ying</creatorcontrib><creatorcontrib>Liu, Jing-Tao</creatorcontrib><creatorcontrib>Fang, Jian</creatorcontrib><creatorcontrib>Zhang, Yan-Hua</creatorcontrib><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><jtitle>Journal of pharmacy and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ma, Xu</au><au>Han, Sen</au><au>Liu, Ying</au><au>Liu, Jing-Tao</au><au>Fang, Jian</au><au>Zhang, Yan-Hua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacogenetic impact of UGT1A1 polymorphisms on pulmonary neuroendocrine tumours treated with metronomic irinotecan-based chemotherapy in Chinese populations</atitle><jtitle>Journal of pharmacy and pharmacology</jtitle><date>2020-11</date><risdate>2020</risdate><volume>72</volume><issue>11</issue><spage>1528</spage><epage>1535</epage><pages>1528-1535</pages><issn>0022-3573</issn><eissn>2042-7158</eissn><abstract>Abstract
Objectives
To evaluate the effects of UGT1A1*6 and UGT1A1*28 polymorphisms on the safety and efficacy of metronomic irinotecan-based chemotherapy (IBC) in Chinese patients with pulmonary neuroendocrine tumours (PNTs).
Methods
Sixty-eight PNT patients who received metronomic IBC were observed. The quantitative fluorescent polymerase chain reaction was used to detect UGT1A1*6 and UGT1A1*28 polymorphisms. The follow-up data were collected to investigate the relationship between different genotypes and adverse drug reactions. The clinical outcomes of metronomic IBC were also evaluated.
Key findings
In the genotype–toxicity association analysis, patients with homozygous UGT1A1*6 had the highest incidence of grade 3-4 diarrhoea (P = 0.010). Compared to other groups, patients with the haplotype of UGT1A1*28 showed a trend towards an increased incidence of grade 4 neutropaenia (P = 0.047). A higher incidence of grade 3–4 leucopaenia was found in groups with UGT1A1*1/*28 (P = 0.023) and UGT1A1*28/*28 (P = 0.022). Grade 1 total bilirubin elevation was associated with the homozygous UGT1A1*6 mutation (P = 0.027) or any UGT1A1*6 variants (P = 0.047). However, neither UGTA1A*28 nor UGT1A1*6 showed any significant association with tumour response or clinical outcomes.
Conclusions
The impact of UGT1A1 polymorphisms varies in different irinotecan-based chemotherapies. UGT1A1*6 and UGTA1A*28 were useful for the prediction of irinotecan-related severe toxicity in Chinese PNT patients treated with metronomic IBC.</abstract><cop>Bognor Regis</cop><pub>Oxford University Press</pub><doi>10.1111/jphp.13333</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-1649-2284</orcidid><orcidid>https://orcid.org/0000-0003-4344-574X</orcidid><orcidid>https://orcid.org/0000-0002-5891-5225</orcidid><orcidid>https://orcid.org/0000-0002-3340-5958</orcidid><orcidid>https://orcid.org/0000-0002-2752-7270</orcidid><orcidid>https://orcid.org/0000-0003-3697-4563</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); Wiley Online Library Journals Frontfile Complete |
| subjects | Association analysis Bilirubin Chemotherapy Clinical outcomes Diarrhea Haplotypes Irinotecan Neuroendocrine tumors Polymerase chain reaction pulmonary neuroendocrine tumour single nucleotide polymorphisms Toxicity UGT1A128 UGT1A16 |
| title | Pharmacogenetic impact of UGT1A1 polymorphisms on pulmonary neuroendocrine tumours treated with metronomic irinotecan-based chemotherapy in Chinese populations |
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