The efficacy and safety of cardio-protective therapy in patients with 5-FU (Fluorouracil)-associated coronary vasospasm
Coronary vasospasm is a known side effect of 5-FU (fluorouracil) therapy. Beyond switching to non-5FU-based chemotherapy, there are no established treatments for 5-FU associated coronary vasospam. Our objective was to assess the safety and efficacy of re-challenge with 5-FU after pre-treatment with...
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| Veröffentlicht in: | PloS one 2022-04, Vol.17 (4), p.e0265767-e0265767 |
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| creator | Zafar, Amna Drobni, Zsofia D Lei, Matthew Gongora, Carlos A Quinaglia, Thiago Lou, Uvette Y Mosarla, Ramya Murphy, Sean P Jones-O'Connor, Maeve Mahmood, Ali Hartmann, Sarah Gilman, Hannah K Weekes, Colin D Nipp, Ryan Clark, John R Clark, Jeffrey W Blaszkowsky, Lawrence S Tavares, Erica Neilan, Tomas G |
| description | Coronary vasospasm is a known side effect of 5-FU (fluorouracil) therapy. Beyond switching to non-5FU-based chemotherapy, there are no established treatments for 5-FU associated coronary vasospam. Our objective was to assess the safety and efficacy of re-challenge with 5-FU after pre-treatment with calcium channel blockers (CCBs) and long-acting nitrates among patients 5-FU associated coronary vasospasm.
We conducted a retrospective study of patients with 5-FU coronary vasospasm at a single academic center. By protocol, those referred to cardio-oncology received pre-treatment with either combination [nitrates and CCBs] or single-agent therapy [nitrates or CCBs]) prior to re-challenge with 5-FU. Our primary outcome was overall survival. Other important outcomes included progression-free survival and safety.
Among 6,606 patients who received 5-FU from January 2001 to Dec 2020, 115 (1.74%) developed coronary vasospasm. Of these 115 patients, 81 patients continued 5-FU therapy, while 34 stopped. Of the 81 who continued, 78 were referred to cardio-oncology and prescribed CCBs and/or nitrates prior to subsequent 5-FU, while the remaining 3 continued 5-FU without cardiac pre-treatment. Of the 78, 56.4% (44/78) received both nitrates and CCBs, 19.2% (15/78) received CCBs alone, and 24.4% (19/78) received nitrates alone. When compared to patients who stopped 5-FU, those who continued 5-FU after pre-treatment (single or combination therapy) had a decreased risk of death (HR 0.42, P = 0.005 [95% CI 0.23-0.77]) and a trend towards decreased cancer progression (HR 0.60, P = 0.08 [95% CI 0.34-1.06]). No patient in the pre-treatment group had a myocardial infarct after re-challenge; however, chest pain (without myocardial infarction) recurred in 19.2% (15/78) among those who received cardiac pre-treatment vs. 66.7% (2/3) among those who did not (P = 0.048). There was no difference in efficacy or the recurrence of vasospasm among patients who received pre-treatment with a single agent (nitrates or CCBs) or combination therapy (14.7% (5/34) vs. 25.0% (11/44), P = 0.26).
Re-challenge after pre-treatment with CCBs and nitrates guided by a cardio-oncology service was safe and allowed continued 5-FU therapy. |
| doi_str_mv | 10.1371/journal.pone.0265767 |
| format | Article |
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We conducted a retrospective study of patients with 5-FU coronary vasospasm at a single academic center. By protocol, those referred to cardio-oncology received pre-treatment with either combination [nitrates and CCBs] or single-agent therapy [nitrates or CCBs]) prior to re-challenge with 5-FU. Our primary outcome was overall survival. Other important outcomes included progression-free survival and safety.
Among 6,606 patients who received 5-FU from January 2001 to Dec 2020, 115 (1.74%) developed coronary vasospasm. Of these 115 patients, 81 patients continued 5-FU therapy, while 34 stopped. Of the 81 who continued, 78 were referred to cardio-oncology and prescribed CCBs and/or nitrates prior to subsequent 5-FU, while the remaining 3 continued 5-FU without cardiac pre-treatment. Of the 78, 56.4% (44/78) received both nitrates and CCBs, 19.2% (15/78) received CCBs alone, and 24.4% (19/78) received nitrates alone. When compared to patients who stopped 5-FU, those who continued 5-FU after pre-treatment (single or combination therapy) had a decreased risk of death (HR 0.42, P = 0.005 [95% CI 0.23-0.77]) and a trend towards decreased cancer progression (HR 0.60, P = 0.08 [95% CI 0.34-1.06]). No patient in the pre-treatment group had a myocardial infarct after re-challenge; however, chest pain (without myocardial infarction) recurred in 19.2% (15/78) among those who received cardiac pre-treatment vs. 66.7% (2/3) among those who did not (P = 0.048). There was no difference in efficacy or the recurrence of vasospasm among patients who received pre-treatment with a single agent (nitrates or CCBs) or combination therapy (14.7% (5/34) vs. 25.0% (11/44), P = 0.26).
Re-challenge after pre-treatment with CCBs and nitrates guided by a cardio-oncology service was safe and allowed continued 5-FU therapy.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0265767</identifier><identifier>PMID: 35390017</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>5-Fluorouracil ; Biology and Life Sciences ; Calcium channel blockers ; Calcium Channel Blockers - therapeutic use ; Calcium channels ; Cardiology ; Cardiotoxicity ; Cardiovascular disease ; Care and treatment ; Chemotherapy ; Colorectal cancer ; Complications and side effects ; Coronary heart disease ; Coronary Vasospasm - chemically induced ; Coronary Vasospasm - drug therapy ; Coronary vessels ; Drug dosages ; Fluorouracil ; Fluorouracil - adverse effects ; Gastrointestinal cancer ; Heart ; Hematology ; Hospitals ; Humans ; Medical schools ; Medicine ; Medicine and Health Sciences ; Myocardial infarction ; Neoplasms - drug therapy ; Nitrates ; Nitrates - therapeutic use ; Oncology ; Pain ; Patient outcomes ; Patients ; Physical Sciences ; Pretreatment ; Retrospective Studies ; Safety ; Survival ; Variables ; Vasoconstriction</subject><ispartof>PloS one, 2022-04, Vol.17 (4), p.e0265767-e0265767</ispartof><rights>COPYRIGHT 2022 Public Library of Science</rights><rights>2022 Zafar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 Zafar et al 2022 Zafar et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c593t-5972f22cef219cf7695826a909a1498822376e45b13969152add810235bd20c13</citedby><cites>FETCH-LOGICAL-c593t-5972f22cef219cf7695826a909a1498822376e45b13969152add810235bd20c13</cites><orcidid>0000-0001-9220-3646 ; 0000-0002-0383-2086 ; 0000-0001-9099-3007 ; 0000-0003-2010-3018</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/PMC8989300/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8989300/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,2104,2930,23873,27931,27932,53798,53800</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35390017$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Taniyama, Yoshiaki</contributor><creatorcontrib>Zafar, Amna</creatorcontrib><creatorcontrib>Drobni, Zsofia D</creatorcontrib><creatorcontrib>Lei, Matthew</creatorcontrib><creatorcontrib>Gongora, Carlos A</creatorcontrib><creatorcontrib>Quinaglia, Thiago</creatorcontrib><creatorcontrib>Lou, Uvette Y</creatorcontrib><creatorcontrib>Mosarla, Ramya</creatorcontrib><creatorcontrib>Murphy, Sean P</creatorcontrib><creatorcontrib>Jones-O'Connor, Maeve</creatorcontrib><creatorcontrib>Mahmood, Ali</creatorcontrib><creatorcontrib>Hartmann, Sarah</creatorcontrib><creatorcontrib>Gilman, Hannah K</creatorcontrib><creatorcontrib>Weekes, Colin D</creatorcontrib><creatorcontrib>Nipp, Ryan</creatorcontrib><creatorcontrib>Clark, John R</creatorcontrib><creatorcontrib>Clark, Jeffrey W</creatorcontrib><creatorcontrib>Blaszkowsky, Lawrence S</creatorcontrib><creatorcontrib>Tavares, Erica</creatorcontrib><creatorcontrib>Neilan, Tomas G</creatorcontrib><title>The efficacy and safety of cardio-protective therapy in patients with 5-FU (Fluorouracil)-associated coronary vasospasm</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Coronary vasospasm is a known side effect of 5-FU (fluorouracil) therapy. Beyond switching to non-5FU-based chemotherapy, there are no established treatments for 5-FU associated coronary vasospam. Our objective was to assess the safety and efficacy of re-challenge with 5-FU after pre-treatment with calcium channel blockers (CCBs) and long-acting nitrates among patients 5-FU associated coronary vasospasm.
We conducted a retrospective study of patients with 5-FU coronary vasospasm at a single academic center. By protocol, those referred to cardio-oncology received pre-treatment with either combination [nitrates and CCBs] or single-agent therapy [nitrates or CCBs]) prior to re-challenge with 5-FU. Our primary outcome was overall survival. Other important outcomes included progression-free survival and safety.
Among 6,606 patients who received 5-FU from January 2001 to Dec 2020, 115 (1.74%) developed coronary vasospasm. Of these 115 patients, 81 patients continued 5-FU therapy, while 34 stopped. Of the 81 who continued, 78 were referred to cardio-oncology and prescribed CCBs and/or nitrates prior to subsequent 5-FU, while the remaining 3 continued 5-FU without cardiac pre-treatment. Of the 78, 56.4% (44/78) received both nitrates and CCBs, 19.2% (15/78) received CCBs alone, and 24.4% (19/78) received nitrates alone. When compared to patients who stopped 5-FU, those who continued 5-FU after pre-treatment (single or combination therapy) had a decreased risk of death (HR 0.42, P = 0.005 [95% CI 0.23-0.77]) and a trend towards decreased cancer progression (HR 0.60, P = 0.08 [95% CI 0.34-1.06]). No patient in the pre-treatment group had a myocardial infarct after re-challenge; however, chest pain (without myocardial infarction) recurred in 19.2% (15/78) among those who received cardiac pre-treatment vs. 66.7% (2/3) among those who did not (P = 0.048). There was no difference in efficacy or the recurrence of vasospasm among patients who received pre-treatment with a single agent (nitrates or CCBs) or combination therapy (14.7% (5/34) vs. 25.0% (11/44), P = 0.26).
Re-challenge after pre-treatment with CCBs and nitrates guided by a cardio-oncology service was safe and allowed continued 5-FU therapy.</description><subject>5-Fluorouracil</subject><subject>Biology and Life Sciences</subject><subject>Calcium channel blockers</subject><subject>Calcium Channel Blockers - therapeutic use</subject><subject>Calcium channels</subject><subject>Cardiology</subject><subject>Cardiotoxicity</subject><subject>Cardiovascular disease</subject><subject>Care and treatment</subject><subject>Chemotherapy</subject><subject>Colorectal cancer</subject><subject>Complications and side effects</subject><subject>Coronary heart disease</subject><subject>Coronary Vasospasm - chemically induced</subject><subject>Coronary Vasospasm - drug therapy</subject><subject>Coronary vessels</subject><subject>Drug dosages</subject><subject>Fluorouracil</subject><subject>Fluorouracil - adverse effects</subject><subject>Gastrointestinal cancer</subject><subject>Heart</subject><subject>Hematology</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Medical schools</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Myocardial infarction</subject><subject>Neoplasms - drug therapy</subject><subject>Nitrates</subject><subject>Nitrates - therapeutic use</subject><subject>Oncology</subject><subject>Pain</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Physical Sciences</subject><subject>Pretreatment</subject><subject>Retrospective Studies</subject><subject>Safety</subject><subject>Survival</subject><subject>Variables</subject><subject>Vasoconstriction</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNptUl1r2zAUNWNj7br9g7EJ9tI9ONOHJUsvg1KWrVDYS_ssbvSRKDiWJzkp-fdTFrc0oxhhcXXOuedeTlV9JHhGWEu-reM29dDNhti7GaaCt6J9VZ0TxWgtKGavn93Pqnc5rzHmTArxtjpjnCmMSXtePdytHHLeBwNmj6C3KIN34x5FjwwkG2I9pDg6M4adQ-PKJRj2KPRogDG4fszoIYwrxOv5Pbqcd9uYii0woftaQ87RBBidRaaUe0h7tIMc8wB5875646HL7sP0v6ju5z_urn_Vt79_3lxf3daGKzbWXLXUU2qcp0QZ3wrFJRWgsALSKCkpZa1wDV8QpoQinIK1kmDK-MJSbAi7qD4fdYcuZj3tLGsqGkkVEVIWxM0RYSOs9ZDCphjVEYL-V4hpqSGNwXROY0yLA6DEtrLhTCyoZE46XJo1i5bZovV96rZdbJw1ZUEJuhPR05c-rPQy7rRUUjGMi8DlJJDin63Lo96EbFzXQe_i9uhbYVpOgX75D_rydBNqCWWA0PtY-pqDqL4SSrVEyUYU1OwFVPms2wRTAuZDqZ8QmiPBpJhzcv5pRoL1IZ6PZvQhnnqKZ6F9er6fJ9JjHtlfPN_haA</recordid><startdate>20220407</startdate><enddate>20220407</enddate><creator>Zafar, 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efficacy and safety of cardio-protective therapy in patients with 5-FU (Fluorouracil)-associated coronary vasospasm</title><author>Zafar, Amna ; Drobni, Zsofia D ; Lei, Matthew ; Gongora, Carlos A ; Quinaglia, Thiago ; Lou, Uvette Y ; Mosarla, Ramya ; Murphy, Sean P ; Jones-O'Connor, Maeve ; Mahmood, Ali ; Hartmann, Sarah ; Gilman, Hannah K ; Weekes, Colin D ; Nipp, Ryan ; Clark, John R ; Clark, Jeffrey W ; Blaszkowsky, Lawrence S ; Tavares, Erica ; Neilan, Tomas G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c593t-5972f22cef219cf7695826a909a1498822376e45b13969152add810235bd20c13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>5-Fluorouracil</topic><topic>Biology and Life Sciences</topic><topic>Calcium channel blockers</topic><topic>Calcium Channel Blockers - therapeutic use</topic><topic>Calcium 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Database</collection><collection>Materials Science Collection</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>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zafar, Amna</au><au>Drobni, Zsofia D</au><au>Lei, Matthew</au><au>Gongora, Carlos A</au><au>Quinaglia, Thiago</au><au>Lou, Uvette Y</au><au>Mosarla, Ramya</au><au>Murphy, Sean P</au><au>Jones-O'Connor, Maeve</au><au>Mahmood, Ali</au><au>Hartmann, Sarah</au><au>Gilman, Hannah K</au><au>Weekes, Colin D</au><au>Nipp, Ryan</au><au>Clark, John R</au><au>Clark, Jeffrey W</au><au>Blaszkowsky, Lawrence S</au><au>Tavares, Erica</au><au>Neilan, Tomas G</au><au>Taniyama, Yoshiaki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The efficacy and safety of cardio-protective therapy in patients with 5-FU (Fluorouracil)-associated coronary vasospasm</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2022-04-07</date><risdate>2022</risdate><volume>17</volume><issue>4</issue><spage>e0265767</spage><epage>e0265767</epage><pages>e0265767-e0265767</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Coronary vasospasm is a known side effect of 5-FU (fluorouracil) therapy. Beyond switching to non-5FU-based chemotherapy, there are no established treatments for 5-FU associated coronary vasospam. Our objective was to assess the safety and efficacy of re-challenge with 5-FU after pre-treatment with calcium channel blockers (CCBs) and long-acting nitrates among patients 5-FU associated coronary vasospasm.
We conducted a retrospective study of patients with 5-FU coronary vasospasm at a single academic center. By protocol, those referred to cardio-oncology received pre-treatment with either combination [nitrates and CCBs] or single-agent therapy [nitrates or CCBs]) prior to re-challenge with 5-FU. Our primary outcome was overall survival. Other important outcomes included progression-free survival and safety.
Among 6,606 patients who received 5-FU from January 2001 to Dec 2020, 115 (1.74%) developed coronary vasospasm. Of these 115 patients, 81 patients continued 5-FU therapy, while 34 stopped. Of the 81 who continued, 78 were referred to cardio-oncology and prescribed CCBs and/or nitrates prior to subsequent 5-FU, while the remaining 3 continued 5-FU without cardiac pre-treatment. Of the 78, 56.4% (44/78) received both nitrates and CCBs, 19.2% (15/78) received CCBs alone, and 24.4% (19/78) received nitrates alone. When compared to patients who stopped 5-FU, those who continued 5-FU after pre-treatment (single or combination therapy) had a decreased risk of death (HR 0.42, P = 0.005 [95% CI 0.23-0.77]) and a trend towards decreased cancer progression (HR 0.60, P = 0.08 [95% CI 0.34-1.06]). No patient in the pre-treatment group had a myocardial infarct after re-challenge; however, chest pain (without myocardial infarction) recurred in 19.2% (15/78) among those who received cardiac pre-treatment vs. 66.7% (2/3) among those who did not (P = 0.048). There was no difference in efficacy or the recurrence of vasospasm among patients who received pre-treatment with a single agent (nitrates or CCBs) or combination therapy (14.7% (5/34) vs. 25.0% (11/44), P = 0.26).
Re-challenge after pre-treatment with CCBs and nitrates guided by a cardio-oncology service was safe and allowed continued 5-FU therapy.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>35390017</pmid><doi>10.1371/journal.pone.0265767</doi><orcidid>https://orcid.org/0000-0001-9220-3646</orcidid><orcidid>https://orcid.org/0000-0002-0383-2086</orcidid><orcidid>https://orcid.org/0000-0001-9099-3007</orcidid><orcidid>https://orcid.org/0000-0003-2010-3018</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2022-04, Vol.17 (4), p.e0265767-e0265767 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2648291688 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 5-Fluorouracil Biology and Life Sciences Calcium channel blockers Calcium Channel Blockers - therapeutic use Calcium channels Cardiology Cardiotoxicity Cardiovascular disease Care and treatment Chemotherapy Colorectal cancer Complications and side effects Coronary heart disease Coronary Vasospasm - chemically induced Coronary Vasospasm - drug therapy Coronary vessels Drug dosages Fluorouracil Fluorouracil - adverse effects Gastrointestinal cancer Heart Hematology Hospitals Humans Medical schools Medicine Medicine and Health Sciences Myocardial infarction Neoplasms - drug therapy Nitrates Nitrates - therapeutic use Oncology Pain Patient outcomes Patients Physical Sciences Pretreatment Retrospective Studies Safety Survival Variables Vasoconstriction |
| title | The efficacy and safety of cardio-protective therapy in patients with 5-FU (Fluorouracil)-associated coronary vasospasm |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-03T23%3A26%3A39IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20efficacy%20and%20safety%20of%20cardio-protective%20therapy%20in%20patients%20with%205-FU%20(Fluorouracil)-associated%20coronary%20vasospasm&rft.jtitle=PloS%20one&rft.au=Zafar,%20Amna&rft.date=2022-04-07&rft.volume=17&rft.issue=4&rft.spage=e0265767&rft.epage=e0265767&rft.pages=e0265767-e0265767&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0265767&rft_dat=%3Cgale_plos_%3EA699719846%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2648291688&rft_id=info:pmid/35390017&rft_galeid=A699719846&rft_doaj_id=oai_doaj_org_article_002769a21d784536b283e8e05bd4b73d&rfr_iscdi=true |