Activity of preclinical and phase I clinical trial of a novel androgen receptor antagonist GT0918 in metastatic breast cancer
Purpose To evaluate GT0918, a 2nd-generation AR antagonist, for its AR down-regulation activity among breast cancer patients. Methods The effect of GT0918 on AR protein expression was evaluated in AR expression breast cancer cells and in breast cancer xenograft model. A 3 + 3 phase I dose-escalation...
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| Veröffentlicht in: | Breast cancer research and treatment 2021-10, Vol.189 (3), p.725-736 |
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| creator | Li, Huiping Song, Guohong Zhou, Qiaoxia Ran, Ran Jiang, Hanfang Zhang, Ruyan Liu, Yaxin Zhang, Jiayang Meng, Luping Ma, Liandong Sun, Ye Wang, Meiyu Zhou, Qingqing Yan, Honghua Zhou, Qianxiang Dong, Xunwei Tong, Youzhi |
| description | Purpose
To evaluate GT0918, a 2nd-generation AR antagonist, for its AR down-regulation activity among breast cancer patients.
Methods
The effect of GT0918 on AR protein expression was evaluated in AR expression breast cancer cells and in breast cancer xenograft model. A 3 + 3 phase I dose-escalation study was launched in Peking University Cancer Hospital. The endpoints included dose finding, safety, pharmacokinetics, and antitumor activity.
Results
GT0918 was demonstrated to effectively suppress the expression of AR protein and the growth of AR-positive breast cancer tumors in mouse xenograft tumor models. All patients treated with GT0918 were at a QD dose-escalation of five dose levels from 100 to 500 mg. The most common treatment-related AEs of any grade were asthenia, anemia, decreased appetite, increased blood cholesterol, increased blood triglycerides, decreased white blood cell count, and increased low-density lipoprotein. Grade 3 AEs were fatigue (2 of 18, 11.1%), aspartate aminotransferase increase (1 of 18, 5.6%), alanine aminotransferase increase (1 of 18, 5.6%), and neutrophil count decrease (1 of 18, 5.6%). Clinical benefit rate (CBR) in 16 weeks was 23.1% (3/13). Among 7 AR-positive patients, 6 can evaluate efficacy, and 2 completed 23.5- and 25-cycle treatment, respectively (as of 2020/1/20). PK parameters showed a fast absorption profile of GT0918 in the single-dose study. GT0918 and its major metabolite reached steady-state serum concentration levels at day 21 after multiple dosing.
Conclusion
GT0918 can effectively inhibit AR-positive breast cancer tumor growth. GT0918 was demonstrated well tolerated with a favorable PK profile. The suitable dose of GT0918 was 500 mg QD and may provide clinical benefits for AR-positive mBC. |
| doi_str_mv | 10.1007/s10549-021-06345-x |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8505310</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A678748986</galeid><sourcerecordid>A678748986</sourcerecordid><originalsourceid>FETCH-LOGICAL-c572t-feea7c45cefa1b54c8fc531801a3348c4339a3937861270841c6912239e42f43</originalsourceid><addsrcrecordid>eNp9kl9rHCEUxaW0NNu0X6APRSj0bVL_js5LYQltEgj0Zd_Fde_MGmZ0q-6SPOS712TTTRZCEVSuv3P0ykHoMyVnlBD1PVMiRdcQRhvSciGb2zdoRqXijWJUvUUzQlvVtJq0J-hDzjeEkE6R7j064YJ3TEg-Q_dzV_zOlzsce7xJ4EYfvLMjtmGFN2ubAV_hQ7EkX-dKWhziDh6pFAcIuCphU2KqlWKHGHwu-GJBOqqxD3iCYnOxxTu8TFC32NngIH1E73o7Zvj0tJ6ixa-fi_PL5vr3xdX5_LpxUrHS9ABWOSEd9JYupXC6d5JTTajlXGgnOO8s77jSLWWKaEFd21HGeAeC9YKfoh972812OcHKQSjJjmaT_GTTnYnWm-OT4NdmiDujJan3kGrw9ckgxT9byMXcxG0K9cmGSU00U1qJZ2qwIxgf-ljN3OSzM_P2gdCdbit19gpVxwom72KA3tf6keDbC8Ea7FjWOY7b4mPIxyDbgy7FnBP0hw4pMQ-JMfvEmJoY85gYc1tFX17-zUHyLyIV4Hsg16MwQHru_T-2fwEAQctl</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2580827874</pqid></control><display><type>article</type><title>Activity of preclinical and phase I clinical trial of a novel androgen receptor antagonist GT0918 in metastatic breast cancer</title><source>MEDLINE</source><source>SpringerNature Journals</source><creator>Li, Huiping ; Song, Guohong ; Zhou, Qiaoxia ; Ran, Ran ; Jiang, Hanfang ; Zhang, Ruyan ; Liu, Yaxin ; Zhang, Jiayang ; Meng, Luping ; Ma, Liandong ; Sun, Ye ; Wang, Meiyu ; Zhou, Qingqing ; Yan, Honghua ; Zhou, Qianxiang ; Dong, Xunwei ; Tong, Youzhi</creator><creatorcontrib>Li, Huiping ; Song, Guohong ; Zhou, Qiaoxia ; Ran, Ran ; Jiang, Hanfang ; Zhang, Ruyan ; Liu, Yaxin ; Zhang, Jiayang ; Meng, Luping ; Ma, Liandong ; Sun, Ye ; Wang, Meiyu ; Zhou, Qingqing ; Yan, Honghua ; Zhou, Qianxiang ; Dong, Xunwei ; Tong, Youzhi</creatorcontrib><description>Purpose
To evaluate GT0918, a 2nd-generation AR antagonist, for its AR down-regulation activity among breast cancer patients.
Methods
The effect of GT0918 on AR protein expression was evaluated in AR expression breast cancer cells and in breast cancer xenograft model. A 3 + 3 phase I dose-escalation study was launched in Peking University Cancer Hospital. The endpoints included dose finding, safety, pharmacokinetics, and antitumor activity.
Results
GT0918 was demonstrated to effectively suppress the expression of AR protein and the growth of AR-positive breast cancer tumors in mouse xenograft tumor models. All patients treated with GT0918 were at a QD dose-escalation of five dose levels from 100 to 500 mg. The most common treatment-related AEs of any grade were asthenia, anemia, decreased appetite, increased blood cholesterol, increased blood triglycerides, decreased white blood cell count, and increased low-density lipoprotein. Grade 3 AEs were fatigue (2 of 18, 11.1%), aspartate aminotransferase increase (1 of 18, 5.6%), alanine aminotransferase increase (1 of 18, 5.6%), and neutrophil count decrease (1 of 18, 5.6%). Clinical benefit rate (CBR) in 16 weeks was 23.1% (3/13). Among 7 AR-positive patients, 6 can evaluate efficacy, and 2 completed 23.5- and 25-cycle treatment, respectively (as of 2020/1/20). PK parameters showed a fast absorption profile of GT0918 in the single-dose study. GT0918 and its major metabolite reached steady-state serum concentration levels at day 21 after multiple dosing.
Conclusion
GT0918 can effectively inhibit AR-positive breast cancer tumor growth. GT0918 was demonstrated well tolerated with a favorable PK profile. The suitable dose of GT0918 was 500 mg QD and may provide clinical benefits for AR-positive mBC.</description><identifier>ISSN: 0167-6806</identifier><identifier>EISSN: 1573-7217</identifier><identifier>DOI: 10.1007/s10549-021-06345-x</identifier><identifier>PMID: 34392453</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Alanine ; Alanine transaminase ; Androgen Receptor Antagonists ; Androgen receptors ; Animal models ; Animals ; Antitumor activity ; Appetite loss ; Aspartate ; Aspartate aminotransferase ; Asthenia ; Blood ; Blood cell count ; Blood cholesterol ; Breast cancer ; Breast Neoplasms - drug therapy ; Cancer research ; Cholesterol ; Clinical Trial ; Clinical trials ; Dosage ; Down-regulation ; Female ; Humans ; Leukocytes (neutrophilic) ; Low density lipoproteins ; Medicine ; Medicine & Public Health ; Metastases ; Metastasis ; Mice ; NCT ; NCT04103853 ; Oncology ; Oxazoles ; Patients ; Pharmacokinetics ; Product development ; Receptors, Androgen ; Thiohydantoins ; Triglycerides ; Tumors ; Xenografts</subject><ispartof>Breast cancer research and treatment, 2021-10, Vol.189 (3), p.725-736</ispartof><rights>The Author(s) 2021</rights><rights>2021. The Author(s).</rights><rights>COPYRIGHT 2021 Springer</rights><rights>The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c572t-feea7c45cefa1b54c8fc531801a3348c4339a3937861270841c6912239e42f43</citedby><cites>FETCH-LOGICAL-c572t-feea7c45cefa1b54c8fc531801a3348c4339a3937861270841c6912239e42f43</cites><orcidid>0000-0002-3331-647X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10549-021-06345-x$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10549-021-06345-x$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34392453$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Huiping</creatorcontrib><creatorcontrib>Song, Guohong</creatorcontrib><creatorcontrib>Zhou, Qiaoxia</creatorcontrib><creatorcontrib>Ran, Ran</creatorcontrib><creatorcontrib>Jiang, Hanfang</creatorcontrib><creatorcontrib>Zhang, Ruyan</creatorcontrib><creatorcontrib>Liu, Yaxin</creatorcontrib><creatorcontrib>Zhang, Jiayang</creatorcontrib><creatorcontrib>Meng, Luping</creatorcontrib><creatorcontrib>Ma, Liandong</creatorcontrib><creatorcontrib>Sun, Ye</creatorcontrib><creatorcontrib>Wang, Meiyu</creatorcontrib><creatorcontrib>Zhou, Qingqing</creatorcontrib><creatorcontrib>Yan, Honghua</creatorcontrib><creatorcontrib>Zhou, Qianxiang</creatorcontrib><creatorcontrib>Dong, Xunwei</creatorcontrib><creatorcontrib>Tong, Youzhi</creatorcontrib><title>Activity of preclinical and phase I clinical trial of a novel androgen receptor antagonist GT0918 in metastatic breast cancer</title><title>Breast cancer research and treatment</title><addtitle>Breast Cancer Res Treat</addtitle><addtitle>Breast Cancer Res Treat</addtitle><description>Purpose
To evaluate GT0918, a 2nd-generation AR antagonist, for its AR down-regulation activity among breast cancer patients.
Methods
The effect of GT0918 on AR protein expression was evaluated in AR expression breast cancer cells and in breast cancer xenograft model. A 3 + 3 phase I dose-escalation study was launched in Peking University Cancer Hospital. The endpoints included dose finding, safety, pharmacokinetics, and antitumor activity.
Results
GT0918 was demonstrated to effectively suppress the expression of AR protein and the growth of AR-positive breast cancer tumors in mouse xenograft tumor models. All patients treated with GT0918 were at a QD dose-escalation of five dose levels from 100 to 500 mg. The most common treatment-related AEs of any grade were asthenia, anemia, decreased appetite, increased blood cholesterol, increased blood triglycerides, decreased white blood cell count, and increased low-density lipoprotein. Grade 3 AEs were fatigue (2 of 18, 11.1%), aspartate aminotransferase increase (1 of 18, 5.6%), alanine aminotransferase increase (1 of 18, 5.6%), and neutrophil count decrease (1 of 18, 5.6%). Clinical benefit rate (CBR) in 16 weeks was 23.1% (3/13). Among 7 AR-positive patients, 6 can evaluate efficacy, and 2 completed 23.5- and 25-cycle treatment, respectively (as of 2020/1/20). PK parameters showed a fast absorption profile of GT0918 in the single-dose study. GT0918 and its major metabolite reached steady-state serum concentration levels at day 21 after multiple dosing.
Conclusion
GT0918 can effectively inhibit AR-positive breast cancer tumor growth. GT0918 was demonstrated well tolerated with a favorable PK profile. The suitable dose of GT0918 was 500 mg QD and may provide clinical benefits for AR-positive mBC.</description><subject>Alanine</subject><subject>Alanine transaminase</subject><subject>Androgen Receptor Antagonists</subject><subject>Androgen receptors</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antitumor activity</subject><subject>Appetite loss</subject><subject>Aspartate</subject><subject>Aspartate aminotransferase</subject><subject>Asthenia</subject><subject>Blood</subject><subject>Blood cell count</subject><subject>Blood cholesterol</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Cancer research</subject><subject>Cholesterol</subject><subject>Clinical Trial</subject><subject>Clinical trials</subject><subject>Dosage</subject><subject>Down-regulation</subject><subject>Female</subject><subject>Humans</subject><subject>Leukocytes (neutrophilic)</subject><subject>Low density lipoproteins</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice</subject><subject>NCT</subject><subject>NCT04103853</subject><subject>Oncology</subject><subject>Oxazoles</subject><subject>Patients</subject><subject>Pharmacokinetics</subject><subject>Product development</subject><subject>Receptors, Androgen</subject><subject>Thiohydantoins</subject><subject>Triglycerides</subject><subject>Tumors</subject><subject>Xenografts</subject><issn>0167-6806</issn><issn>1573-7217</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><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>eNp9kl9rHCEUxaW0NNu0X6APRSj0bVL_js5LYQltEgj0Zd_Fde_MGmZ0q-6SPOS712TTTRZCEVSuv3P0ykHoMyVnlBD1PVMiRdcQRhvSciGb2zdoRqXijWJUvUUzQlvVtJq0J-hDzjeEkE6R7j064YJ3TEg-Q_dzV_zOlzsce7xJ4EYfvLMjtmGFN2ubAV_hQ7EkX-dKWhziDh6pFAcIuCphU2KqlWKHGHwu-GJBOqqxD3iCYnOxxTu8TFC32NngIH1E73o7Zvj0tJ6ixa-fi_PL5vr3xdX5_LpxUrHS9ABWOSEd9JYupXC6d5JTTajlXGgnOO8s77jSLWWKaEFd21HGeAeC9YKfoh972812OcHKQSjJjmaT_GTTnYnWm-OT4NdmiDujJan3kGrw9ckgxT9byMXcxG0K9cmGSU00U1qJZ2qwIxgf-ljN3OSzM_P2gdCdbit19gpVxwom72KA3tf6keDbC8Ea7FjWOY7b4mPIxyDbgy7FnBP0hw4pMQ-JMfvEmJoY85gYc1tFX17-zUHyLyIV4Hsg16MwQHru_T-2fwEAQctl</recordid><startdate>20211001</startdate><enddate>20211001</enddate><creator>Li, Huiping</creator><creator>Song, Guohong</creator><creator>Zhou, Qiaoxia</creator><creator>Ran, Ran</creator><creator>Jiang, Hanfang</creator><creator>Zhang, Ruyan</creator><creator>Liu, Yaxin</creator><creator>Zhang, Jiayang</creator><creator>Meng, Luping</creator><creator>Ma, Liandong</creator><creator>Sun, Ye</creator><creator>Wang, Meiyu</creator><creator>Zhou, Qingqing</creator><creator>Yan, Honghua</creator><creator>Zhou, Qianxiang</creator><creator>Dong, Xunwei</creator><creator>Tong, Youzhi</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>C6C</scope><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>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9-</scope><scope>K9.</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3331-647X</orcidid></search><sort><creationdate>20211001</creationdate><title>Activity of preclinical and phase I clinical trial of a novel androgen receptor antagonist GT0918 in metastatic breast cancer</title><author>Li, Huiping ; Song, Guohong ; Zhou, Qiaoxia ; Ran, Ran ; Jiang, Hanfang ; Zhang, Ruyan ; Liu, Yaxin ; Zhang, Jiayang ; Meng, Luping ; Ma, Liandong ; Sun, Ye ; Wang, Meiyu ; Zhou, Qingqing ; Yan, Honghua ; Zhou, Qianxiang ; Dong, Xunwei ; Tong, Youzhi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c572t-feea7c45cefa1b54c8fc531801a3348c4339a3937861270841c6912239e42f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Alanine</topic><topic>Alanine transaminase</topic><topic>Androgen Receptor Antagonists</topic><topic>Androgen receptors</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antitumor activity</topic><topic>Appetite loss</topic><topic>Aspartate</topic><topic>Aspartate aminotransferase</topic><topic>Asthenia</topic><topic>Blood</topic><topic>Blood cell count</topic><topic>Blood cholesterol</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Cancer research</topic><topic>Cholesterol</topic><topic>Clinical Trial</topic><topic>Clinical trials</topic><topic>Dosage</topic><topic>Down-regulation</topic><topic>Female</topic><topic>Humans</topic><topic>Leukocytes (neutrophilic)</topic><topic>Low density lipoproteins</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mice</topic><topic>NCT</topic><topic>NCT04103853</topic><topic>Oncology</topic><topic>Oxazoles</topic><topic>Patients</topic><topic>Pharmacokinetics</topic><topic>Product development</topic><topic>Receptors, Androgen</topic><topic>Thiohydantoins</topic><topic>Triglycerides</topic><topic>Tumors</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Huiping</creatorcontrib><creatorcontrib>Song, Guohong</creatorcontrib><creatorcontrib>Zhou, Qiaoxia</creatorcontrib><creatorcontrib>Ran, Ran</creatorcontrib><creatorcontrib>Jiang, Hanfang</creatorcontrib><creatorcontrib>Zhang, Ruyan</creatorcontrib><creatorcontrib>Liu, Yaxin</creatorcontrib><creatorcontrib>Zhang, Jiayang</creatorcontrib><creatorcontrib>Meng, Luping</creatorcontrib><creatorcontrib>Ma, Liandong</creatorcontrib><creatorcontrib>Sun, Ye</creatorcontrib><creatorcontrib>Wang, Meiyu</creatorcontrib><creatorcontrib>Zhou, Qingqing</creatorcontrib><creatorcontrib>Yan, Honghua</creatorcontrib><creatorcontrib>Zhou, Qianxiang</creatorcontrib><creatorcontrib>Dong, Xunwei</creatorcontrib><creatorcontrib>Tong, Youzhi</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE 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China</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Breast cancer research and treatment</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Huiping</au><au>Song, Guohong</au><au>Zhou, Qiaoxia</au><au>Ran, Ran</au><au>Jiang, Hanfang</au><au>Zhang, Ruyan</au><au>Liu, Yaxin</au><au>Zhang, Jiayang</au><au>Meng, Luping</au><au>Ma, Liandong</au><au>Sun, Ye</au><au>Wang, Meiyu</au><au>Zhou, Qingqing</au><au>Yan, Honghua</au><au>Zhou, Qianxiang</au><au>Dong, Xunwei</au><au>Tong, Youzhi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activity of preclinical and phase I clinical trial of a novel androgen receptor antagonist GT0918 in metastatic breast cancer</atitle><jtitle>Breast cancer research and treatment</jtitle><stitle>Breast Cancer Res Treat</stitle><addtitle>Breast Cancer Res Treat</addtitle><date>2021-10-01</date><risdate>2021</risdate><volume>189</volume><issue>3</issue><spage>725</spage><epage>736</epage><pages>725-736</pages><issn>0167-6806</issn><eissn>1573-7217</eissn><abstract>Purpose
To evaluate GT0918, a 2nd-generation AR antagonist, for its AR down-regulation activity among breast cancer patients.
Methods
The effect of GT0918 on AR protein expression was evaluated in AR expression breast cancer cells and in breast cancer xenograft model. A 3 + 3 phase I dose-escalation study was launched in Peking University Cancer Hospital. The endpoints included dose finding, safety, pharmacokinetics, and antitumor activity.
Results
GT0918 was demonstrated to effectively suppress the expression of AR protein and the growth of AR-positive breast cancer tumors in mouse xenograft tumor models. All patients treated with GT0918 were at a QD dose-escalation of five dose levels from 100 to 500 mg. The most common treatment-related AEs of any grade were asthenia, anemia, decreased appetite, increased blood cholesterol, increased blood triglycerides, decreased white blood cell count, and increased low-density lipoprotein. Grade 3 AEs were fatigue (2 of 18, 11.1%), aspartate aminotransferase increase (1 of 18, 5.6%), alanine aminotransferase increase (1 of 18, 5.6%), and neutrophil count decrease (1 of 18, 5.6%). Clinical benefit rate (CBR) in 16 weeks was 23.1% (3/13). Among 7 AR-positive patients, 6 can evaluate efficacy, and 2 completed 23.5- and 25-cycle treatment, respectively (as of 2020/1/20). PK parameters showed a fast absorption profile of GT0918 in the single-dose study. GT0918 and its major metabolite reached steady-state serum concentration levels at day 21 after multiple dosing.
Conclusion
GT0918 can effectively inhibit AR-positive breast cancer tumor growth. GT0918 was demonstrated well tolerated with a favorable PK profile. The suitable dose of GT0918 was 500 mg QD and may provide clinical benefits for AR-positive mBC.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>34392453</pmid><doi>10.1007/s10549-021-06345-x</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-3331-647X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0167-6806 |
| ispartof | Breast cancer research and treatment, 2021-10, Vol.189 (3), p.725-736 |
| issn | 0167-6806 1573-7217 |
| language | eng |
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| source | MEDLINE; SpringerNature Journals |
| subjects | Alanine Alanine transaminase Androgen Receptor Antagonists Androgen receptors Animal models Animals Antitumor activity Appetite loss Aspartate Aspartate aminotransferase Asthenia Blood Blood cell count Blood cholesterol Breast cancer Breast Neoplasms - drug therapy Cancer research Cholesterol Clinical Trial Clinical trials Dosage Down-regulation Female Humans Leukocytes (neutrophilic) Low density lipoproteins Medicine Medicine & Public Health Metastases Metastasis Mice NCT NCT04103853 Oncology Oxazoles Patients Pharmacokinetics Product development Receptors, Androgen Thiohydantoins Triglycerides Tumors Xenografts |
| title | Activity of preclinical and phase I clinical trial of a novel androgen receptor antagonist GT0918 in metastatic breast cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-23T20%3A58%3A55IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Activity%20of%20preclinical%20and%20phase%20I%20clinical%20trial%20of%20a%20novel%20androgen%20receptor%20antagonist%20GT0918%20in%20metastatic%20breast%20cancer&rft.jtitle=Breast%20cancer%20research%20and%20treatment&rft.au=Li,%20Huiping&rft.date=2021-10-01&rft.volume=189&rft.issue=3&rft.spage=725&rft.epage=736&rft.pages=725-736&rft.issn=0167-6806&rft.eissn=1573-7217&rft_id=info:doi/10.1007/s10549-021-06345-x&rft_dat=%3Cgale_pubme%3EA678748986%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2580827874&rft_id=info:pmid/34392453&rft_galeid=A678748986&rfr_iscdi=true |