Relationship between Serum Bortezomib Concentration and Emergence of Diarrhea in Patients with Multiple Myeloma and/or AL Amyloidosis
(1) Background: multiple myeloma patients have benefited from bortezomib therapy, though it has often been discontinued owing to diarrhea. The objective of this study was to verify serum bortezomib concentration in the emergence of diarrhea. (2) Methods: this prospective, observational case-control,...
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| Veröffentlicht in: | Cancers 2021-11, Vol.13 (22), p.5674 |
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| creator | Fujimoto, Yuki Ueno, Shikiko Oda, Kazutaka Gunda, Nao Shimomura, Yumi Nishimura, Yuka Yamaguchi, Ayami Kuwano, Akari Ito, Yuki Baba, Yusuke Nishigaki, Aina Michiwaki, Natsumi Uchino, Shota Kurogi, Kayo Kawano, Yawara Matsuoka, Masao Saito, Hideyuki Okuno, Yutaka Jono, Hirofumi |
| description | (1) Background: multiple myeloma patients have benefited from bortezomib therapy, though it has often been discontinued owing to diarrhea. The objective of this study was to verify serum bortezomib concentration in the emergence of diarrhea. (2) Methods: this prospective, observational case-control, and monocentric study was performed with an approval by the Ethics Committee of Kumamoto University Hospital in 2015 (No. 1121) from February 2015 to April 2017. (3) Results: twenty-four patients with bortezomib therapy were recruited; eight patients (33.3%) developed diarrhea at day 3 as median. Median measured trough bortezomib concentration at 24 h after first or second dose for patients with or without diarrhea was 0.87 or 0.48 ng/mL, respectively (p = 0.04, Wilcoxon signed rank test). Receiver operation characteristic (ROC) analysis produced the cut-off concentration of 0.857 ng/mL (area under the ROC curve of 0.797, sensitivity of 0.625, specificity of 0.875). The survival curves between patients with and without diarrhea were similar (p = 0.667); those between patients with higher and lower concentration than median value (0.61 ng/mL) were also similar (p = 0.940). (4) Conclusions: this study indicated the possible involvement of serum bortezomib concentration in the emergence of diarrhea in bortezomib therapy in patients with multiple myeloma. |
| doi_str_mv | 10.3390/cancers13225674 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8616141</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2604028422</sourcerecordid><originalsourceid>FETCH-LOGICAL-c398t-3eba591aed381d3b86d67aa016919c05f2a73c7b9a5308bfe1d1f96d7a94db793</originalsourceid><addsrcrecordid>eNpdkU1rGzEQhkVoaUKac6-CXHpxrY9daXUpuM5HAw4tSXsW2tVsrKCVXGm3wbnnf1eOQ2kzCGaQnnlHL4PQB0o-ca7IvDOhg5QpZ6wWsjpAR4xINhNCVW_-qQ_RSc73pATnVAr5Dh3yquGknCP0dAPejC6GvHYb3ML4ABDwLaRpwF9iGuExDq7Fy1hGhTE9o9gEi88HSHdQbnHs8ZkzKa3BYBfw98IUNOMHN67x9eRHt_GAr7fg42B2vfOY8GKFF8PWR2djdvk9etsbn-HkJR-jnxfnP5ZfZ6tvl1fLxWrWcdWMMw6tqRU1YHlDLW8bYYU0hlChqOpI3TMjeSdbZepir-2BWtorYaVRlW2l4sfo8153M7UD2L0lrzfJDSZtdTRO__8S3Frfxd-6EVTQihaBjy8CKf6aII96cLkD702AOGXNBKkIayrGCnr6Cr2PUwrF3o5ihMpaNYWa76kuxZwT9H8_Q4nebVm_2jL_A2vbnT8</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2602017598</pqid></control><display><type>article</type><title>Relationship between Serum Bortezomib Concentration and Emergence of Diarrhea in Patients with Multiple Myeloma and/or AL Amyloidosis</title><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central Open Access</source><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>PubMed Central</source><creator>Fujimoto, Yuki ; Ueno, Shikiko ; Oda, Kazutaka ; Gunda, Nao ; Shimomura, Yumi ; Nishimura, Yuka ; Yamaguchi, Ayami ; Kuwano, Akari ; Ito, Yuki ; Baba, Yusuke ; Nishigaki, Aina ; Michiwaki, Natsumi ; Uchino, Shota ; Kurogi, Kayo ; Kawano, Yawara ; Matsuoka, Masao ; Saito, Hideyuki ; Okuno, Yutaka ; Jono, Hirofumi</creator><creatorcontrib>Fujimoto, Yuki ; Ueno, Shikiko ; Oda, Kazutaka ; Gunda, Nao ; Shimomura, Yumi ; Nishimura, Yuka ; Yamaguchi, Ayami ; Kuwano, Akari ; Ito, Yuki ; Baba, Yusuke ; Nishigaki, Aina ; Michiwaki, Natsumi ; Uchino, Shota ; Kurogi, Kayo ; Kawano, Yawara ; Matsuoka, Masao ; Saito, Hideyuki ; Okuno, Yutaka ; Jono, Hirofumi</creatorcontrib><description>(1) Background: multiple myeloma patients have benefited from bortezomib therapy, though it has often been discontinued owing to diarrhea. The objective of this study was to verify serum bortezomib concentration in the emergence of diarrhea. (2) Methods: this prospective, observational case-control, and monocentric study was performed with an approval by the Ethics Committee of Kumamoto University Hospital in 2015 (No. 1121) from February 2015 to April 2017. (3) Results: twenty-four patients with bortezomib therapy were recruited; eight patients (33.3%) developed diarrhea at day 3 as median. Median measured trough bortezomib concentration at 24 h after first or second dose for patients with or without diarrhea was 0.87 or 0.48 ng/mL, respectively (p = 0.04, Wilcoxon signed rank test). Receiver operation characteristic (ROC) analysis produced the cut-off concentration of 0.857 ng/mL (area under the ROC curve of 0.797, sensitivity of 0.625, specificity of 0.875). The survival curves between patients with and without diarrhea were similar (p = 0.667); those between patients with higher and lower concentration than median value (0.61 ng/mL) were also similar (p = 0.940). (4) Conclusions: this study indicated the possible involvement of serum bortezomib concentration in the emergence of diarrhea in bortezomib therapy in patients with multiple myeloma.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers13225674</identifier><identifier>PMID: 34830830</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Accuracy ; Acids ; Amyloidosis ; Bortezomib ; Chromatography ; Diarrhea ; Drug dosages ; Multiple myeloma ; Patients ; Peripheral neuropathy ; Pharmacokinetics ; Regression analysis</subject><ispartof>Cancers, 2021-11, Vol.13 (22), p.5674</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c398t-3eba591aed381d3b86d67aa016919c05f2a73c7b9a5308bfe1d1f96d7a94db793</citedby><cites>FETCH-LOGICAL-c398t-3eba591aed381d3b86d67aa016919c05f2a73c7b9a5308bfe1d1f96d7a94db793</cites><orcidid>0000-0002-8269-440X ; 0000-0003-0095-9580 ; 0000-0003-2108-5157</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616141/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616141/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,886,27926,27927,53793,53795</link.rule.ids></links><search><creatorcontrib>Fujimoto, Yuki</creatorcontrib><creatorcontrib>Ueno, Shikiko</creatorcontrib><creatorcontrib>Oda, Kazutaka</creatorcontrib><creatorcontrib>Gunda, Nao</creatorcontrib><creatorcontrib>Shimomura, Yumi</creatorcontrib><creatorcontrib>Nishimura, Yuka</creatorcontrib><creatorcontrib>Yamaguchi, Ayami</creatorcontrib><creatorcontrib>Kuwano, Akari</creatorcontrib><creatorcontrib>Ito, Yuki</creatorcontrib><creatorcontrib>Baba, Yusuke</creatorcontrib><creatorcontrib>Nishigaki, Aina</creatorcontrib><creatorcontrib>Michiwaki, Natsumi</creatorcontrib><creatorcontrib>Uchino, Shota</creatorcontrib><creatorcontrib>Kurogi, Kayo</creatorcontrib><creatorcontrib>Kawano, Yawara</creatorcontrib><creatorcontrib>Matsuoka, Masao</creatorcontrib><creatorcontrib>Saito, Hideyuki</creatorcontrib><creatorcontrib>Okuno, Yutaka</creatorcontrib><creatorcontrib>Jono, Hirofumi</creatorcontrib><title>Relationship between Serum Bortezomib Concentration and Emergence of Diarrhea in Patients with Multiple Myeloma and/or AL Amyloidosis</title><title>Cancers</title><description>(1) Background: multiple myeloma patients have benefited from bortezomib therapy, though it has often been discontinued owing to diarrhea. The objective of this study was to verify serum bortezomib concentration in the emergence of diarrhea. (2) Methods: this prospective, observational case-control, and monocentric study was performed with an approval by the Ethics Committee of Kumamoto University Hospital in 2015 (No. 1121) from February 2015 to April 2017. (3) Results: twenty-four patients with bortezomib therapy were recruited; eight patients (33.3%) developed diarrhea at day 3 as median. Median measured trough bortezomib concentration at 24 h after first or second dose for patients with or without diarrhea was 0.87 or 0.48 ng/mL, respectively (p = 0.04, Wilcoxon signed rank test). Receiver operation characteristic (ROC) analysis produced the cut-off concentration of 0.857 ng/mL (area under the ROC curve of 0.797, sensitivity of 0.625, specificity of 0.875). The survival curves between patients with and without diarrhea were similar (p = 0.667); those between patients with higher and lower concentration than median value (0.61 ng/mL) were also similar (p = 0.940). (4) Conclusions: this study indicated the possible involvement of serum bortezomib concentration in the emergence of diarrhea in bortezomib therapy in patients with multiple myeloma.</description><subject>Accuracy</subject><subject>Acids</subject><subject>Amyloidosis</subject><subject>Bortezomib</subject><subject>Chromatography</subject><subject>Diarrhea</subject><subject>Drug dosages</subject><subject>Multiple myeloma</subject><subject>Patients</subject><subject>Peripheral neuropathy</subject><subject>Pharmacokinetics</subject><subject>Regression analysis</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkU1rGzEQhkVoaUKac6-CXHpxrY9daXUpuM5HAw4tSXsW2tVsrKCVXGm3wbnnf1eOQ2kzCGaQnnlHL4PQB0o-ca7IvDOhg5QpZ6wWsjpAR4xINhNCVW_-qQ_RSc73pATnVAr5Dh3yquGknCP0dAPejC6GvHYb3ML4ABDwLaRpwF9iGuExDq7Fy1hGhTE9o9gEi88HSHdQbnHs8ZkzKa3BYBfw98IUNOMHN67x9eRHt_GAr7fg42B2vfOY8GKFF8PWR2djdvk9etsbn-HkJR-jnxfnP5ZfZ6tvl1fLxWrWcdWMMw6tqRU1YHlDLW8bYYU0hlChqOpI3TMjeSdbZepir-2BWtorYaVRlW2l4sfo8153M7UD2L0lrzfJDSZtdTRO__8S3Frfxd-6EVTQihaBjy8CKf6aII96cLkD702AOGXNBKkIayrGCnr6Cr2PUwrF3o5ihMpaNYWa76kuxZwT9H8_Q4nebVm_2jL_A2vbnT8</recordid><startdate>20211112</startdate><enddate>20211112</enddate><creator>Fujimoto, Yuki</creator><creator>Ueno, Shikiko</creator><creator>Oda, Kazutaka</creator><creator>Gunda, Nao</creator><creator>Shimomura, Yumi</creator><creator>Nishimura, Yuka</creator><creator>Yamaguchi, Ayami</creator><creator>Kuwano, Akari</creator><creator>Ito, Yuki</creator><creator>Baba, Yusuke</creator><creator>Nishigaki, Aina</creator><creator>Michiwaki, Natsumi</creator><creator>Uchino, Shota</creator><creator>Kurogi, Kayo</creator><creator>Kawano, Yawara</creator><creator>Matsuoka, Masao</creator><creator>Saito, Hideyuki</creator><creator>Okuno, Yutaka</creator><creator>Jono, Hirofumi</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8269-440X</orcidid><orcidid>https://orcid.org/0000-0003-0095-9580</orcidid><orcidid>https://orcid.org/0000-0003-2108-5157</orcidid></search><sort><creationdate>20211112</creationdate><title>Relationship between Serum Bortezomib Concentration and Emergence of Diarrhea in Patients with Multiple Myeloma and/or AL Amyloidosis</title><author>Fujimoto, Yuki ; Ueno, Shikiko ; Oda, Kazutaka ; Gunda, Nao ; Shimomura, Yumi ; Nishimura, Yuka ; Yamaguchi, Ayami ; Kuwano, Akari ; Ito, Yuki ; Baba, Yusuke ; Nishigaki, Aina ; Michiwaki, Natsumi ; Uchino, Shota ; Kurogi, Kayo ; Kawano, Yawara ; Matsuoka, Masao ; Saito, Hideyuki ; Okuno, Yutaka ; Jono, Hirofumi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c398t-3eba591aed381d3b86d67aa016919c05f2a73c7b9a5308bfe1d1f96d7a94db793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Accuracy</topic><topic>Acids</topic><topic>Amyloidosis</topic><topic>Bortezomib</topic><topic>Chromatography</topic><topic>Diarrhea</topic><topic>Drug dosages</topic><topic>Multiple myeloma</topic><topic>Patients</topic><topic>Peripheral neuropathy</topic><topic>Pharmacokinetics</topic><topic>Regression analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fujimoto, Yuki</creatorcontrib><creatorcontrib>Ueno, Shikiko</creatorcontrib><creatorcontrib>Oda, Kazutaka</creatorcontrib><creatorcontrib>Gunda, Nao</creatorcontrib><creatorcontrib>Shimomura, Yumi</creatorcontrib><creatorcontrib>Nishimura, Yuka</creatorcontrib><creatorcontrib>Yamaguchi, Ayami</creatorcontrib><creatorcontrib>Kuwano, Akari</creatorcontrib><creatorcontrib>Ito, Yuki</creatorcontrib><creatorcontrib>Baba, Yusuke</creatorcontrib><creatorcontrib>Nishigaki, Aina</creatorcontrib><creatorcontrib>Michiwaki, Natsumi</creatorcontrib><creatorcontrib>Uchino, Shota</creatorcontrib><creatorcontrib>Kurogi, Kayo</creatorcontrib><creatorcontrib>Kawano, Yawara</creatorcontrib><creatorcontrib>Matsuoka, Masao</creatorcontrib><creatorcontrib>Saito, Hideyuki</creatorcontrib><creatorcontrib>Okuno, Yutaka</creatorcontrib><creatorcontrib>Jono, Hirofumi</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Access via ProQuest (Open Access)</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><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fujimoto, Yuki</au><au>Ueno, Shikiko</au><au>Oda, Kazutaka</au><au>Gunda, Nao</au><au>Shimomura, Yumi</au><au>Nishimura, Yuka</au><au>Yamaguchi, Ayami</au><au>Kuwano, Akari</au><au>Ito, Yuki</au><au>Baba, Yusuke</au><au>Nishigaki, Aina</au><au>Michiwaki, Natsumi</au><au>Uchino, Shota</au><au>Kurogi, Kayo</au><au>Kawano, Yawara</au><au>Matsuoka, Masao</au><au>Saito, Hideyuki</au><au>Okuno, Yutaka</au><au>Jono, Hirofumi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Relationship between Serum Bortezomib Concentration and Emergence of Diarrhea in Patients with Multiple Myeloma and/or AL Amyloidosis</atitle><jtitle>Cancers</jtitle><date>2021-11-12</date><risdate>2021</risdate><volume>13</volume><issue>22</issue><spage>5674</spage><pages>5674-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>(1) Background: multiple myeloma patients have benefited from bortezomib therapy, though it has often been discontinued owing to diarrhea. The objective of this study was to verify serum bortezomib concentration in the emergence of diarrhea. (2) Methods: this prospective, observational case-control, and monocentric study was performed with an approval by the Ethics Committee of Kumamoto University Hospital in 2015 (No. 1121) from February 2015 to April 2017. (3) Results: twenty-four patients with bortezomib therapy were recruited; eight patients (33.3%) developed diarrhea at day 3 as median. Median measured trough bortezomib concentration at 24 h after first or second dose for patients with or without diarrhea was 0.87 or 0.48 ng/mL, respectively (p = 0.04, Wilcoxon signed rank test). Receiver operation characteristic (ROC) analysis produced the cut-off concentration of 0.857 ng/mL (area under the ROC curve of 0.797, sensitivity of 0.625, specificity of 0.875). The survival curves between patients with and without diarrhea were similar (p = 0.667); those between patients with higher and lower concentration than median value (0.61 ng/mL) were also similar (p = 0.940). (4) Conclusions: this study indicated the possible involvement of serum bortezomib concentration in the emergence of diarrhea in bortezomib therapy in patients with multiple myeloma.</abstract><cop>Basel</cop><pub>MDPI AG</pub><pmid>34830830</pmid><doi>10.3390/cancers13225674</doi><orcidid>https://orcid.org/0000-0002-8269-440X</orcidid><orcidid>https://orcid.org/0000-0003-0095-9580</orcidid><orcidid>https://orcid.org/0000-0003-2108-5157</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; PubMed Central |
| subjects | Accuracy Acids Amyloidosis Bortezomib Chromatography Diarrhea Drug dosages Multiple myeloma Patients Peripheral neuropathy Pharmacokinetics Regression analysis |
| title | Relationship between Serum Bortezomib Concentration and Emergence of Diarrhea in Patients with Multiple Myeloma and/or AL Amyloidosis |
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