From Bench to Bedside: Attempt to Evaluate Repositioning of Drugs in the Treatment of Metastatic Small Cell Lung Cancer (SCLC)
Based on in vitro data and results of a recent drug repositioning study, some medications approved by the FDA for the treatment of various non-malignant disorders were demonstrated to have anti-SCLC activity in preclinical models. The aim of our study is to confirm whether use of these medications i...
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| description | Based on in vitro data and results of a recent drug repositioning study, some medications approved by the FDA for the treatment of various non-malignant disorders were demonstrated to have anti-SCLC activity in preclinical models. The aim of our study is to confirm whether use of these medications is associated with survival benefit.
Consecutive patients with pathologically confirmed, stage 4 SCLC were analyzed in this retrospective study. Patients that were prescribed statins, aspirin, clomipramine (tricyclic antidepressant; TCA), selective serotonin reuptake inhibitors (SSRIs), doxazosin or prazosin (α1-adrenergic receptor antagonists; ADRA1) were identified.
There were a total of 876 patients. Aspirin, statins, SSRIs, ADRA1, and TCA were administered in 138, 72, 20, 28, and 5 cases, respectively. A statistically significant increase in median OS was observed only in statin-treated patients when compared to those not receiving any of the aforementioned medications (OS, 8.4 vs. 6.1 months, respectively; p = 0.002). The administration of SSRIs, aspirin, and ADRA1 did not result in a statistically significant OS benefit (median OS, 8.5, 6.8, and 6.0 months, respectively). The multivariate Cox model showed that, besides age and ECOG PS, radiotherapy was an independent survival predictor (Hazard Ratio, 2.151; 95% confidence interval, 1.828-2.525; p |
| doi_str_mv | 10.1371/journal.pone.0144797 |
| format | Article |
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Consecutive patients with pathologically confirmed, stage 4 SCLC were analyzed in this retrospective study. Patients that were prescribed statins, aspirin, clomipramine (tricyclic antidepressant; TCA), selective serotonin reuptake inhibitors (SSRIs), doxazosin or prazosin (α1-adrenergic receptor antagonists; ADRA1) were identified.
There were a total of 876 patients. Aspirin, statins, SSRIs, ADRA1, and TCA were administered in 138, 72, 20, 28, and 5 cases, respectively. A statistically significant increase in median OS was observed only in statin-treated patients when compared to those not receiving any of the aforementioned medications (OS, 8.4 vs. 6.1 months, respectively; p = 0.002). The administration of SSRIs, aspirin, and ADRA1 did not result in a statistically significant OS benefit (median OS, 8.5, 6.8, and 6.0 months, respectively). The multivariate Cox model showed that, besides age and ECOG PS, radiotherapy was an independent survival predictor (Hazard Ratio, 2.151; 95% confidence interval, 1.828-2.525; p <0.001).
Results of drug repositioning studies using only preclinical data or small numbers of patients should be treated with caution before application in the clinic. Our data demonstrated that radiotherapy appears to be an independent survival predictor in stage 4 SCLC, therefore confirming the results of other prospective and retrospective studies.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0144797</identifier><identifier>PMID: 26735301</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adrenergic receptors ; Adult ; Aged ; Aged, 80 and over ; Analysis ; Antidepressants ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - therapeutic use ; Aspirin ; Cancer metastasis ; Cancer therapies ; Care and treatment ; Chemotherapy ; Clinical medicine ; Clomipramine ; Complications and side effects ; Confidence intervals ; Data processing ; Development and progression ; Drug development ; Drug dosages ; Drug Repositioning - statistics & numerical data ; Drugs ; Ethics ; FDA approval ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - chemistry ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use ; Kaplan-Meier Estimate ; Laboratories ; Lung cancer ; Lung diseases ; Lung Neoplasms - mortality ; Lung Neoplasms - pathology ; Lung Neoplasms - therapy ; Male ; Mathematical models ; Metastases ; Metastasis ; Middle Aged ; Neoplasm Staging ; Oncology ; Patient outcomes ; Patients ; Prazosin ; Proportional Hazards Models ; Radiation therapy ; Retrospective Studies ; Selective serotonin reuptake inhibitors ; Serotonin ; Serotonin uptake inhibitors ; Small cell lung cancer ; Small cell lung carcinoma ; Small Cell Lung Carcinoma - mortality ; Small Cell Lung Carcinoma - pathology ; Small Cell Lung Carcinoma - therapy ; Statins ; Statistical analysis ; Statistical significance ; Studies ; Survival ; Systematic review ; Thoracic surgery ; Tumors</subject><ispartof>PloS one, 2016-01, Vol.11 (1), p.e0144797-e0144797</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Lohinai 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>2016 Lohinai et al 2016 Lohinai et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-5ebdd1abd1c917150ff48215c004830217a1711e586b4c083485f4e3480a57603</citedby><cites>FETCH-LOGICAL-c692t-5ebdd1abd1c917150ff48215c004830217a1711e586b4c083485f4e3480a57603</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703211/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703211/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26735301$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Minna, John D</contributor><creatorcontrib>Lohinai, Zoltan</creatorcontrib><creatorcontrib>Dome, Peter</creatorcontrib><creatorcontrib>Szilagyi, Zsuzsa</creatorcontrib><creatorcontrib>Ostoros, Gyula</creatorcontrib><creatorcontrib>Moldvay, Judit</creatorcontrib><creatorcontrib>Hegedus, Balazs</creatorcontrib><creatorcontrib>Dome, Balazs</creatorcontrib><creatorcontrib>Weiss, Glen J</creatorcontrib><title>From Bench to Bedside: Attempt to Evaluate Repositioning of Drugs in the Treatment of Metastatic Small Cell Lung Cancer (SCLC)</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Based on in vitro data and results of a recent drug repositioning study, some medications approved by the FDA for the treatment of various non-malignant disorders were demonstrated to have anti-SCLC activity in preclinical models. The aim of our study is to confirm whether use of these medications is associated with survival benefit.
Consecutive patients with pathologically confirmed, stage 4 SCLC were analyzed in this retrospective study. Patients that were prescribed statins, aspirin, clomipramine (tricyclic antidepressant; TCA), selective serotonin reuptake inhibitors (SSRIs), doxazosin or prazosin (α1-adrenergic receptor antagonists; ADRA1) were identified.
There were a total of 876 patients. Aspirin, statins, SSRIs, ADRA1, and TCA were administered in 138, 72, 20, 28, and 5 cases, respectively. A statistically significant increase in median OS was observed only in statin-treated patients when compared to those not receiving any of the aforementioned medications (OS, 8.4 vs. 6.1 months, respectively; p = 0.002). The administration of SSRIs, aspirin, and ADRA1 did not result in a statistically significant OS benefit (median OS, 8.5, 6.8, and 6.0 months, respectively). The multivariate Cox model showed that, besides age and ECOG PS, radiotherapy was an independent survival predictor (Hazard Ratio, 2.151; 95% confidence interval, 1.828-2.525; p <0.001).
Results of drug repositioning studies using only preclinical data or small numbers of patients should be treated with caution before application in the clinic. Our data demonstrated that radiotherapy appears to be an independent survival predictor in stage 4 SCLC, therefore confirming the results of other prospective and retrospective studies.</description><subject>Adrenergic receptors</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analysis</subject><subject>Antidepressants</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Aspirin</subject><subject>Cancer metastasis</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Chemotherapy</subject><subject>Clinical medicine</subject><subject>Clomipramine</subject><subject>Complications and side effects</subject><subject>Confidence intervals</subject><subject>Data processing</subject><subject>Development and progression</subject><subject>Drug development</subject><subject>Drug dosages</subject><subject>Drug Repositioning - statistics & numerical data</subject><subject>Drugs</subject><subject>Ethics</subject><subject>FDA approval</subject><subject>Female</subject><subject>Humans</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - chemistry</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</subject><subject>Kaplan-Meier Estimate</subject><subject>Laboratories</subject><subject>Lung cancer</subject><subject>Lung diseases</subject><subject>Lung Neoplasms - mortality</subject><subject>Lung Neoplasms - pathology</subject><subject>Lung Neoplasms - therapy</subject><subject>Male</subject><subject>Mathematical models</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>Oncology</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Prazosin</subject><subject>Proportional Hazards Models</subject><subject>Radiation therapy</subject><subject>Retrospective Studies</subject><subject>Selective serotonin reuptake inhibitors</subject><subject>Serotonin</subject><subject>Serotonin uptake inhibitors</subject><subject>Small cell lung cancer</subject><subject>Small cell lung carcinoma</subject><subject>Small Cell Lung Carcinoma - mortality</subject><subject>Small Cell Lung Carcinoma - pathology</subject><subject>Small Cell Lung Carcinoma - therapy</subject><subject>Statins</subject><subject>Statistical analysis</subject><subject>Statistical significance</subject><subject>Studies</subject><subject>Survival</subject><subject>Systematic review</subject><subject>Thoracic surgery</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</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>eNqNk1Fv0zAQxyMEYmPwDRBEQkLbQ4sdO07CA1IJG1QqmrQOXq2rc2k9JXGxnQle-Ow4tJsatAdkKbbOv__fubMvil5SMqUso-9uTG87aKZb0-GUUM6zInsUHdOCJROREPb4YH0UPXPuhpCU5UI8jY4SkbGUEXoc_b6wpo0_Yqc2sTdhUTld4ft45j22Wz_Ezm-h6cFjfIVb47TXptPdOjZ1_Mn2axfrLvYbjK8tgm-x88POV_TgPHit4mULTROXGD6LPuhK6BTa-HRZLsqz59GTGhqHL_bzSfTt4vy6_DJZXH6el7PFRIki8ZMUV1VFYVVRVdCMpqSueZ7QVBHCc0YSmkEIU0xzseKK5Iznac0xTATSTBB2Er3e-W4b4-S-dE7SLOUkyVjOAzHfEZWBG7m1ugX7SxrQ8m_A2LUEG_JpUNZBscIqQZGmPAEBVVEAwzypVjlTCQSvD_vT-lWLlQpFsdCMTMc7nd7ItbmVPCMsoTQYnO4NrPnRo_Oy1U6FEkKHph_-W5A8zYhgAX3zD_pwdntqDSEB3dUmnKsGUznjrKCCiDwP1PQBKowKW63CO6t1iI8EZyNBYDz-9GvonZPz5dX_s5ffx-zbA3aD0PiNM00_vD03BvkOVNY4Z7G-LzIlcmiTu2rIoU3kvk2C7NXhBd2L7vqC_QGmuQrE</recordid><startdate>20160106</startdate><enddate>20160106</enddate><creator>Lohinai, Zoltan</creator><creator>Dome, Peter</creator><creator>Szilagyi, Zsuzsa</creator><creator>Ostoros, Gyula</creator><creator>Moldvay, Judit</creator><creator>Hegedus, Balazs</creator><creator>Dome, Balazs</creator><creator>Weiss, Glen J</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160106</creationdate><title>From Bench to Bedside: Attempt to Evaluate Repositioning of Drugs in the Treatment of Metastatic Small Cell Lung Cancer (SCLC)</title><author>Lohinai, Zoltan ; Dome, Peter ; Szilagyi, Zsuzsa ; Ostoros, Gyula ; Moldvay, Judit ; Hegedus, Balazs ; Dome, Balazs ; Weiss, Glen J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-5ebdd1abd1c917150ff48215c004830217a1711e586b4c083485f4e3480a57603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adrenergic receptors</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Analysis</topic><topic>Antidepressants</topic><topic>Antineoplastic Agents - 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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>Lohinai, Zoltan</au><au>Dome, Peter</au><au>Szilagyi, Zsuzsa</au><au>Ostoros, Gyula</au><au>Moldvay, Judit</au><au>Hegedus, Balazs</au><au>Dome, Balazs</au><au>Weiss, Glen J</au><au>Minna, John D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>From Bench to Bedside: Attempt to Evaluate Repositioning of Drugs in the Treatment of Metastatic Small Cell Lung Cancer (SCLC)</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-01-06</date><risdate>2016</risdate><volume>11</volume><issue>1</issue><spage>e0144797</spage><epage>e0144797</epage><pages>e0144797-e0144797</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Based on in vitro data and results of a recent drug repositioning study, some medications approved by the FDA for the treatment of various non-malignant disorders were demonstrated to have anti-SCLC activity in preclinical models. The aim of our study is to confirm whether use of these medications is associated with survival benefit.
Consecutive patients with pathologically confirmed, stage 4 SCLC were analyzed in this retrospective study. Patients that were prescribed statins, aspirin, clomipramine (tricyclic antidepressant; TCA), selective serotonin reuptake inhibitors (SSRIs), doxazosin or prazosin (α1-adrenergic receptor antagonists; ADRA1) were identified.
There were a total of 876 patients. Aspirin, statins, SSRIs, ADRA1, and TCA were administered in 138, 72, 20, 28, and 5 cases, respectively. A statistically significant increase in median OS was observed only in statin-treated patients when compared to those not receiving any of the aforementioned medications (OS, 8.4 vs. 6.1 months, respectively; p = 0.002). The administration of SSRIs, aspirin, and ADRA1 did not result in a statistically significant OS benefit (median OS, 8.5, 6.8, and 6.0 months, respectively). The multivariate Cox model showed that, besides age and ECOG PS, radiotherapy was an independent survival predictor (Hazard Ratio, 2.151; 95% confidence interval, 1.828-2.525; p <0.001).
Results of drug repositioning studies using only preclinical data or small numbers of patients should be treated with caution before application in the clinic. Our data demonstrated that radiotherapy appears to be an independent survival predictor in stage 4 SCLC, therefore confirming the results of other prospective and retrospective studies.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26735301</pmid><doi>10.1371/journal.pone.0144797</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2016-01, Vol.11 (1), p.e0144797-e0144797 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1754027384 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adrenergic receptors Adult Aged Aged, 80 and over Analysis Antidepressants Antineoplastic Agents - chemistry Antineoplastic Agents - therapeutic use Aspirin Cancer metastasis Cancer therapies Care and treatment Chemotherapy Clinical medicine Clomipramine Complications and side effects Confidence intervals Data processing Development and progression Drug development Drug dosages Drug Repositioning - statistics & numerical data Drugs Ethics FDA approval Female Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - chemistry Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use Kaplan-Meier Estimate Laboratories Lung cancer Lung diseases Lung Neoplasms - mortality Lung Neoplasms - pathology Lung Neoplasms - therapy Male Mathematical models Metastases Metastasis Middle Aged Neoplasm Staging Oncology Patient outcomes Patients Prazosin Proportional Hazards Models Radiation therapy Retrospective Studies Selective serotonin reuptake inhibitors Serotonin Serotonin uptake inhibitors Small cell lung cancer Small cell lung carcinoma Small Cell Lung Carcinoma - mortality Small Cell Lung Carcinoma - pathology Small Cell Lung Carcinoma - therapy Statins Statistical analysis Statistical significance Studies Survival Systematic review Thoracic surgery Tumors |
| title | From Bench to Bedside: Attempt to Evaluate Repositioning of Drugs in the Treatment of Metastatic Small Cell Lung Cancer (SCLC) |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T13%3A57%3A01IST&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=From%20Bench%20to%20Bedside:%20Attempt%20to%20Evaluate%20Repositioning%20of%20Drugs%20in%20the%20Treatment%20of%20Metastatic%20Small%20Cell%20Lung%20Cancer%20(SCLC)&rft.jtitle=PloS%20one&rft.au=Lohinai,%20Zoltan&rft.date=2016-01-06&rft.volume=11&rft.issue=1&rft.spage=e0144797&rft.epage=e0144797&rft.pages=e0144797-e0144797&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0144797&rft_dat=%3Cgale_plos_%3EA439160688%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=1754027384&rft_id=info:pmid/26735301&rft_galeid=A439160688&rft_doaj_id=oai_doaj_org_article_f273bed2e65542a6ad99a3e82db83c2a&rfr_iscdi=true |