Association of ABCB1, 5-HT3B Receptor and CYP2D6 Genetic Polymorphisms with Ondansetron and Metoclopramide Antiemetic Response in Indonesian Cancer Patients Treated with Highly Emetogenic Chemotherapy
Objective Suboptimal treatment of chemotherapy-induced nausea and vomiting and unsatisfactory response to antiemetic drugs cause impairment of cancer patient's daily functioning. This study was aimed to investigate the association of selected germline polymorphisms with ondansetron and metoclop...
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| Veröffentlicht in: | Japanese journal of clinical oncology 2011-10, Vol.41 (10), p.1168-1176 |
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| creator | Perwitasari, Dyah A. Wessels, Judith A.M. van der Straaten, Robert J.H.M. Baak-Pablo, Renee F. Mustofa, Mustofa Hakimi, Mohammad Nortier, Johann W.R. Gelderblom, Hans Guchelaar, Henk-Jan |
| description | Objective
Suboptimal treatment of chemotherapy-induced nausea and vomiting and unsatisfactory response to antiemetic drugs cause impairment of cancer patient's daily functioning. This study was aimed to investigate the association of selected germline polymorphisms with ondansetron and metoclopramide response in Indonesian cancer patients treated with highly emetogenic chemotherapy.
Methods
We enrolled 202 chemotherapy naïve patients treated with cisplatin at a dosage of ≥50 mg/m2 as monotherapy or as combined chemotherapy. Ondansetron 8 mg and dexamethasone 8 mg intravenously were the standard antiemetic therapy for prevention of acute chemotherapy-induced nausea and vomiting. Metoclopramide 10 mg orally, three times per day as fixed prescription, was given until 5 days after chemotherapy to prevent delayed chemotherapy-induced nausea and vomiting. Primary and secondary outcomes were the occurrence of chemotherapy-induced nausea and vomiting in the acute and delayed phase. The following single-nucleotide polymorphisms were determined in ABCB1: rs1045642, rs2032582 and rs1128503; in 5-HT3B-R: rs45460698, rs4938058 and rs7943062; and in CYP2D6: rs16947 (CYP2D6*2), rs3892097 (CYP2D6*4) and rs1065852 (CYP2D6*10) using Taqman assays.
Results
During the acute phase, 21.8 and 30.2% patients experienced Grade 3 and 4 nausea and vomiting, respectively, whereas 38.6% patients experienced nausea and/or vomiting in the delayed phase. Carriers of the CTG haplotype of the ABCB1 gene experienced Grade 3 and 4 chemotherapy-induced nausea and vomiting more often than other haplotypes in the delayed phase (P< 0.05). No associations were found with the 5-HT3B receptor haplotypes and CYP2D6-predicted phenotypes.
Conclusions
Our study shows that in Indonesian cancer patients treated with highly cytostatic emetogenic, carriership of the CTG haplotype of the ABCB1 gene is related to an increased risk of delayed chemotherapy-induced nausea and vomiting. |
| doi_str_mv | 10.1093/jjco/hyr117 |
| format | Article |
| fullrecord | <record><control><sourceid>oup_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1093_jjco_hyr117</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/jjco/hyr117</oup_id><sourcerecordid>10.1093/jjco/hyr117</sourcerecordid><originalsourceid>FETCH-LOGICAL-c380t-a0184a0c1fb1edf9b775c534bb6eed17f411a87282b44a4aeb7ccd1f6aa17c0f3</originalsourceid><addsrcrecordid>eNp9kU1v1DAQQC0EokvhxB35xIWGevLl9LgbSrdSUVfVcuAUTexJ49XGjmxXKP-Qn9UsAY6c5vLmaUaPsfcgPoO4yi4PB-Uu-8kDyBdsBXlZJFmZwku2EllZJWkFcMbehHAQQhRVLl-zsxSqXFRSrNivdQhOGYzGWe46vt7UG7jgRbLdZxv-QIrG6DxHq3n9Y5d-KfkNWYpG8Z07ToPzY2_CEPhPE3t-bzXaQNHPrtPGN4pOHd3ocTCa-NpGQ8Pv5QcKo5tRbiy_tdpZCgYtr9Eq8nw3n0M2Br73hJH0Yt-ax_448evZ4B7Jzpa6p8HFnjyO01v2qsNjoHd_5jn7_vV6X2-Tu_ub23p9l6isEjFBMb-OQkHXAunuqpWyUEWWt21JpEF2OQBWMq3SNs8xR2qlUhq6EhGkEl12zj4tXuVdCJ66ZvRmQD81IJpTj-bUo1l6zPSHhR6f2oH0P_ZvgBn4uADuafyv6Rl3gJju</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Association of ABCB1, 5-HT3B Receptor and CYP2D6 Genetic Polymorphisms with Ondansetron and Metoclopramide Antiemetic Response in Indonesian Cancer Patients Treated with Highly Emetogenic Chemotherapy</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>Alma/SFX Local Collection</source><creator>Perwitasari, Dyah A. ; Wessels, Judith A.M. ; van der Straaten, Robert J.H.M. ; Baak-Pablo, Renee F. ; Mustofa, Mustofa ; Hakimi, Mohammad ; Nortier, Johann W.R. ; Gelderblom, Hans ; Guchelaar, Henk-Jan</creator><creatorcontrib>Perwitasari, Dyah A. ; Wessels, Judith A.M. ; van der Straaten, Robert J.H.M. ; Baak-Pablo, Renee F. ; Mustofa, Mustofa ; Hakimi, Mohammad ; Nortier, Johann W.R. ; Gelderblom, Hans ; Guchelaar, Henk-Jan</creatorcontrib><description>Objective
Suboptimal treatment of chemotherapy-induced nausea and vomiting and unsatisfactory response to antiemetic drugs cause impairment of cancer patient's daily functioning. This study was aimed to investigate the association of selected germline polymorphisms with ondansetron and metoclopramide response in Indonesian cancer patients treated with highly emetogenic chemotherapy.
Methods
We enrolled 202 chemotherapy naïve patients treated with cisplatin at a dosage of ≥50 mg/m2 as monotherapy or as combined chemotherapy. Ondansetron 8 mg and dexamethasone 8 mg intravenously were the standard antiemetic therapy for prevention of acute chemotherapy-induced nausea and vomiting. Metoclopramide 10 mg orally, three times per day as fixed prescription, was given until 5 days after chemotherapy to prevent delayed chemotherapy-induced nausea and vomiting. Primary and secondary outcomes were the occurrence of chemotherapy-induced nausea and vomiting in the acute and delayed phase. The following single-nucleotide polymorphisms were determined in ABCB1: rs1045642, rs2032582 and rs1128503; in 5-HT3B-R: rs45460698, rs4938058 and rs7943062; and in CYP2D6: rs16947 (CYP2D6*2), rs3892097 (CYP2D6*4) and rs1065852 (CYP2D6*10) using Taqman assays.
Results
During the acute phase, 21.8 and 30.2% patients experienced Grade 3 and 4 nausea and vomiting, respectively, whereas 38.6% patients experienced nausea and/or vomiting in the delayed phase. Carriers of the CTG haplotype of the ABCB1 gene experienced Grade 3 and 4 chemotherapy-induced nausea and vomiting more often than other haplotypes in the delayed phase (P< 0.05). No associations were found with the 5-HT3B receptor haplotypes and CYP2D6-predicted phenotypes.
Conclusions
Our study shows that in Indonesian cancer patients treated with highly cytostatic emetogenic, carriership of the CTG haplotype of the ABCB1 gene is related to an increased risk of delayed chemotherapy-induced nausea and vomiting.</description><identifier>ISSN: 0368-2811</identifier><identifier>EISSN: 1465-3621</identifier><identifier>DOI: 10.1093/jjco/hyr117</identifier><identifier>PMID: 21840870</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Antiemetics - pharmacokinetics ; Antiemetics - pharmacology ; Antineoplastic Agents - adverse effects ; ATP Binding Cassette Transporter, Sub-Family B ; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics ; Cisplatin - adverse effects ; Cytochrome P-450 CYP2D6 - genetics ; Female ; Haplotypes - genetics ; Humans ; Indonesia ; Male ; Metoclopramide - pharmacokinetics ; Metoclopramide - pharmacology ; Middle Aged ; Nausea - chemically induced ; Nausea - genetics ; Neoplasms - drug therapy ; Ondansetron - pharmacokinetics ; Ondansetron - pharmacology ; Polymorphism, Single Nucleotide ; Receptors, Serotonin, 5-HT3 - genetics ; Vomiting - chemically induced ; Vomiting - genetics</subject><ispartof>Japanese journal of clinical oncology, 2011-10, Vol.41 (10), p.1168-1176</ispartof><rights>The Author (2011). Published by Oxford University Press. All rights reserved 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c380t-a0184a0c1fb1edf9b775c534bb6eed17f411a87282b44a4aeb7ccd1f6aa17c0f3</citedby><cites>FETCH-LOGICAL-c380t-a0184a0c1fb1edf9b775c534bb6eed17f411a87282b44a4aeb7ccd1f6aa17c0f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21840870$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Perwitasari, Dyah A.</creatorcontrib><creatorcontrib>Wessels, Judith A.M.</creatorcontrib><creatorcontrib>van der Straaten, Robert J.H.M.</creatorcontrib><creatorcontrib>Baak-Pablo, Renee F.</creatorcontrib><creatorcontrib>Mustofa, Mustofa</creatorcontrib><creatorcontrib>Hakimi, Mohammad</creatorcontrib><creatorcontrib>Nortier, Johann W.R.</creatorcontrib><creatorcontrib>Gelderblom, Hans</creatorcontrib><creatorcontrib>Guchelaar, Henk-Jan</creatorcontrib><title>Association of ABCB1, 5-HT3B Receptor and CYP2D6 Genetic Polymorphisms with Ondansetron and Metoclopramide Antiemetic Response in Indonesian Cancer Patients Treated with Highly Emetogenic Chemotherapy</title><title>Japanese journal of clinical oncology</title><addtitle>Jpn J Clin Oncol</addtitle><description>Objective
Suboptimal treatment of chemotherapy-induced nausea and vomiting and unsatisfactory response to antiemetic drugs cause impairment of cancer patient's daily functioning. This study was aimed to investigate the association of selected germline polymorphisms with ondansetron and metoclopramide response in Indonesian cancer patients treated with highly emetogenic chemotherapy.
Methods
We enrolled 202 chemotherapy naïve patients treated with cisplatin at a dosage of ≥50 mg/m2 as monotherapy or as combined chemotherapy. Ondansetron 8 mg and dexamethasone 8 mg intravenously were the standard antiemetic therapy for prevention of acute chemotherapy-induced nausea and vomiting. Metoclopramide 10 mg orally, three times per day as fixed prescription, was given until 5 days after chemotherapy to prevent delayed chemotherapy-induced nausea and vomiting. Primary and secondary outcomes were the occurrence of chemotherapy-induced nausea and vomiting in the acute and delayed phase. The following single-nucleotide polymorphisms were determined in ABCB1: rs1045642, rs2032582 and rs1128503; in 5-HT3B-R: rs45460698, rs4938058 and rs7943062; and in CYP2D6: rs16947 (CYP2D6*2), rs3892097 (CYP2D6*4) and rs1065852 (CYP2D6*10) using Taqman assays.
Results
During the acute phase, 21.8 and 30.2% patients experienced Grade 3 and 4 nausea and vomiting, respectively, whereas 38.6% patients experienced nausea and/or vomiting in the delayed phase. Carriers of the CTG haplotype of the ABCB1 gene experienced Grade 3 and 4 chemotherapy-induced nausea and vomiting more often than other haplotypes in the delayed phase (P< 0.05). No associations were found with the 5-HT3B receptor haplotypes and CYP2D6-predicted phenotypes.
Conclusions
Our study shows that in Indonesian cancer patients treated with highly cytostatic emetogenic, carriership of the CTG haplotype of the ABCB1 gene is related to an increased risk of delayed chemotherapy-induced nausea and vomiting.</description><subject>Antiemetics - pharmacokinetics</subject><subject>Antiemetics - pharmacology</subject><subject>Antineoplastic Agents - adverse effects</subject><subject>ATP Binding Cassette Transporter, Sub-Family B</subject><subject>ATP-Binding Cassette, Sub-Family B, Member 1 - genetics</subject><subject>Cisplatin - adverse effects</subject><subject>Cytochrome P-450 CYP2D6 - genetics</subject><subject>Female</subject><subject>Haplotypes - genetics</subject><subject>Humans</subject><subject>Indonesia</subject><subject>Male</subject><subject>Metoclopramide - pharmacokinetics</subject><subject>Metoclopramide - pharmacology</subject><subject>Middle Aged</subject><subject>Nausea - chemically induced</subject><subject>Nausea - genetics</subject><subject>Neoplasms - drug therapy</subject><subject>Ondansetron - pharmacokinetics</subject><subject>Ondansetron - pharmacology</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Receptors, Serotonin, 5-HT3 - genetics</subject><subject>Vomiting - chemically induced</subject><subject>Vomiting - genetics</subject><issn>0368-2811</issn><issn>1465-3621</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1v1DAQQC0EokvhxB35xIWGevLl9LgbSrdSUVfVcuAUTexJ49XGjmxXKP-Qn9UsAY6c5vLmaUaPsfcgPoO4yi4PB-Uu-8kDyBdsBXlZJFmZwku2EllZJWkFcMbehHAQQhRVLl-zsxSqXFRSrNivdQhOGYzGWe46vt7UG7jgRbLdZxv-QIrG6DxHq3n9Y5d-KfkNWYpG8Z07ToPzY2_CEPhPE3t-bzXaQNHPrtPGN4pOHd3ocTCa-NpGQ8Pv5QcKo5tRbiy_tdpZCgYtr9Eq8nw3n0M2Br73hJH0Yt-ax_448evZ4B7Jzpa6p8HFnjyO01v2qsNjoHd_5jn7_vV6X2-Tu_ub23p9l6isEjFBMb-OQkHXAunuqpWyUEWWt21JpEF2OQBWMq3SNs8xR2qlUhq6EhGkEl12zj4tXuVdCJ66ZvRmQD81IJpTj-bUo1l6zPSHhR6f2oH0P_ZvgBn4uADuafyv6Rl3gJju</recordid><startdate>201110</startdate><enddate>201110</enddate><creator>Perwitasari, Dyah A.</creator><creator>Wessels, Judith A.M.</creator><creator>van der Straaten, Robert J.H.M.</creator><creator>Baak-Pablo, Renee F.</creator><creator>Mustofa, Mustofa</creator><creator>Hakimi, Mohammad</creator><creator>Nortier, Johann W.R.</creator><creator>Gelderblom, Hans</creator><creator>Guchelaar, Henk-Jan</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>201110</creationdate><title>Association of ABCB1, 5-HT3B Receptor and CYP2D6 Genetic Polymorphisms with Ondansetron and Metoclopramide Antiemetic Response in Indonesian Cancer Patients Treated with Highly Emetogenic Chemotherapy</title><author>Perwitasari, Dyah A. ; Wessels, Judith A.M. ; van der Straaten, Robert J.H.M. ; Baak-Pablo, Renee F. ; Mustofa, Mustofa ; Hakimi, Mohammad ; Nortier, Johann W.R. ; Gelderblom, Hans ; Guchelaar, Henk-Jan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c380t-a0184a0c1fb1edf9b775c534bb6eed17f411a87282b44a4aeb7ccd1f6aa17c0f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Antiemetics - pharmacokinetics</topic><topic>Antiemetics - pharmacology</topic><topic>Antineoplastic Agents - adverse effects</topic><topic>ATP Binding Cassette Transporter, Sub-Family B</topic><topic>ATP-Binding Cassette, Sub-Family B, Member 1 - genetics</topic><topic>Cisplatin - adverse effects</topic><topic>Cytochrome P-450 CYP2D6 - genetics</topic><topic>Female</topic><topic>Haplotypes - genetics</topic><topic>Humans</topic><topic>Indonesia</topic><topic>Male</topic><topic>Metoclopramide - pharmacokinetics</topic><topic>Metoclopramide - pharmacology</topic><topic>Middle Aged</topic><topic>Nausea - chemically induced</topic><topic>Nausea - genetics</topic><topic>Neoplasms - drug therapy</topic><topic>Ondansetron - pharmacokinetics</topic><topic>Ondansetron - pharmacology</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Receptors, Serotonin, 5-HT3 - genetics</topic><topic>Vomiting - chemically induced</topic><topic>Vomiting - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Perwitasari, Dyah A.</creatorcontrib><creatorcontrib>Wessels, Judith A.M.</creatorcontrib><creatorcontrib>van der Straaten, Robert J.H.M.</creatorcontrib><creatorcontrib>Baak-Pablo, Renee F.</creatorcontrib><creatorcontrib>Mustofa, Mustofa</creatorcontrib><creatorcontrib>Hakimi, Mohammad</creatorcontrib><creatorcontrib>Nortier, Johann W.R.</creatorcontrib><creatorcontrib>Gelderblom, Hans</creatorcontrib><creatorcontrib>Guchelaar, Henk-Jan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Japanese journal of clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Perwitasari, Dyah A.</au><au>Wessels, Judith A.M.</au><au>van der Straaten, Robert J.H.M.</au><au>Baak-Pablo, Renee F.</au><au>Mustofa, Mustofa</au><au>Hakimi, Mohammad</au><au>Nortier, Johann W.R.</au><au>Gelderblom, Hans</au><au>Guchelaar, Henk-Jan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of ABCB1, 5-HT3B Receptor and CYP2D6 Genetic Polymorphisms with Ondansetron and Metoclopramide Antiemetic Response in Indonesian Cancer Patients Treated with Highly Emetogenic Chemotherapy</atitle><jtitle>Japanese journal of clinical oncology</jtitle><addtitle>Jpn J Clin Oncol</addtitle><date>2011-10</date><risdate>2011</risdate><volume>41</volume><issue>10</issue><spage>1168</spage><epage>1176</epage><pages>1168-1176</pages><issn>0368-2811</issn><eissn>1465-3621</eissn><abstract>Objective
Suboptimal treatment of chemotherapy-induced nausea and vomiting and unsatisfactory response to antiemetic drugs cause impairment of cancer patient's daily functioning. This study was aimed to investigate the association of selected germline polymorphisms with ondansetron and metoclopramide response in Indonesian cancer patients treated with highly emetogenic chemotherapy.
Methods
We enrolled 202 chemotherapy naïve patients treated with cisplatin at a dosage of ≥50 mg/m2 as monotherapy or as combined chemotherapy. Ondansetron 8 mg and dexamethasone 8 mg intravenously were the standard antiemetic therapy for prevention of acute chemotherapy-induced nausea and vomiting. Metoclopramide 10 mg orally, three times per day as fixed prescription, was given until 5 days after chemotherapy to prevent delayed chemotherapy-induced nausea and vomiting. Primary and secondary outcomes were the occurrence of chemotherapy-induced nausea and vomiting in the acute and delayed phase. The following single-nucleotide polymorphisms were determined in ABCB1: rs1045642, rs2032582 and rs1128503; in 5-HT3B-R: rs45460698, rs4938058 and rs7943062; and in CYP2D6: rs16947 (CYP2D6*2), rs3892097 (CYP2D6*4) and rs1065852 (CYP2D6*10) using Taqman assays.
Results
During the acute phase, 21.8 and 30.2% patients experienced Grade 3 and 4 nausea and vomiting, respectively, whereas 38.6% patients experienced nausea and/or vomiting in the delayed phase. Carriers of the CTG haplotype of the ABCB1 gene experienced Grade 3 and 4 chemotherapy-induced nausea and vomiting more often than other haplotypes in the delayed phase (P< 0.05). No associations were found with the 5-HT3B receptor haplotypes and CYP2D6-predicted phenotypes.
Conclusions
Our study shows that in Indonesian cancer patients treated with highly cytostatic emetogenic, carriership of the CTG haplotype of the ABCB1 gene is related to an increased risk of delayed chemotherapy-induced nausea and vomiting.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>21840870</pmid><doi>10.1093/jjco/hyr117</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0368-2811 |
| ispartof | Japanese journal of clinical oncology, 2011-10, Vol.41 (10), p.1168-1176 |
| issn | 0368-2811 1465-3621 |
| language | eng |
| recordid | cdi_crossref_primary_10_1093_jjco_hyr117 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | Antiemetics - pharmacokinetics Antiemetics - pharmacology Antineoplastic Agents - adverse effects ATP Binding Cassette Transporter, Sub-Family B ATP-Binding Cassette, Sub-Family B, Member 1 - genetics Cisplatin - adverse effects Cytochrome P-450 CYP2D6 - genetics Female Haplotypes - genetics Humans Indonesia Male Metoclopramide - pharmacokinetics Metoclopramide - pharmacology Middle Aged Nausea - chemically induced Nausea - genetics Neoplasms - drug therapy Ondansetron - pharmacokinetics Ondansetron - pharmacology Polymorphism, Single Nucleotide Receptors, Serotonin, 5-HT3 - genetics Vomiting - chemically induced Vomiting - genetics |
| title | Association of ABCB1, 5-HT3B Receptor and CYP2D6 Genetic Polymorphisms with Ondansetron and Metoclopramide Antiemetic Response in Indonesian Cancer Patients Treated with Highly Emetogenic Chemotherapy |
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