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[177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study
Progressive metastatic castration-resistant prostate cancer is a highly lethal disorder and new effective therapeutic agents that improve patient outcomes are urgently needed. Lutetium-177 [177Lu]-PSMA-617, a radiolabelled small molecule, binds with high affinity to prostate-specific membrane antige...
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| Published in: | The lancet oncology 2018-06, Vol.19 (6), p.825-833 |
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| creator | Hofman, Michael S Violet, John Hicks, Rodney J Ferdinandus, Justin Thang, Sue Ping Akhurst, Tim Iravani, Amir Kong, Grace Ravi Kumar, Aravind Murphy, Declan G Eu, Peter Jackson, Price Scalzo, Mark Williams, Scott G Sandhu, Shahneen |
| description | Progressive metastatic castration-resistant prostate cancer is a highly lethal disorder and new effective therapeutic agents that improve patient outcomes are urgently needed. Lutetium-177 [177Lu]-PSMA-617, a radiolabelled small molecule, binds with high affinity to prostate-specific membrane antigen (PSMA) enabling beta particle therapy targeted to metastatic castration-resistant prostate cancer. We aimed to investigate the safety, efficacy, and effect on quality of life of [177Lu]-PSMA-617 in men with metastatic castration-resistant prostate cancer who progressed after standard treatments.
In this single-arm, single-centre, phase 2 trial, we recruited men (aged 18 years and older) with metastatic castration-resistant prostate cancer and progressive disease after standard treatments, including taxane-based chemotherapy and second-generation anti-androgens, from the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. Patients underwent a screening PSMA and FDG-PET/CT to confirm high PSMA-expression. Eligible patients had progressive disease defined by imaging (according to Response Evaluation Criteria In Solid Tumours [RECIST] or bone scan) or new pain in an area of radiographically evident disease, and were required to have an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or lower. Eligible patients received up to four cycles of intravenous [177Lu]-PSMA-617, at six weekly intervals. The primary endpoint was PSA response according to Prostate Cancer Clinical Trial Working Group criteria defined as a greater than 50% PSA decline from baseline and toxicity according to CTCAE. Additional primary endpoints were imaging responses (as measured by bone scan, CT, PSMA, and FDG PET/CT) and quality of life (assessed with the EORTC-Q30 and Brief Pain Inventory-Short Form questionnaires), all measured up to 3 months post completion of treatment. This trial is registered with the Australian New Zealand Clinical Trials Registry, number 12615000912583.
Between Aug 26, 2015, and Dec 8, 2016, 43 men were screened to identify 30 patients eligible for treatment. 26 (87%) had received at least one line of previous chemotherapy (80% docetaxel and 47% cabazitaxel) and 25 (83%) received prior abiraterone acetate, enzalutamide, or both. The mean administered radioactivity was 7·5 GBq per cycle. 17 (57%) of 30 patients (95% CI 37–75) achieved a PSA decline of 50% or more. There were no treatment-related deaths. The most common toxic effects related |
| doi_str_mv | 10.1016/S1470-2045(18)30198-0 |
| format | article |
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In this single-arm, single-centre, phase 2 trial, we recruited men (aged 18 years and older) with metastatic castration-resistant prostate cancer and progressive disease after standard treatments, including taxane-based chemotherapy and second-generation anti-androgens, from the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. Patients underwent a screening PSMA and FDG-PET/CT to confirm high PSMA-expression. Eligible patients had progressive disease defined by imaging (according to Response Evaluation Criteria In Solid Tumours [RECIST] or bone scan) or new pain in an area of radiographically evident disease, and were required to have an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or lower. Eligible patients received up to four cycles of intravenous [177Lu]-PSMA-617, at six weekly intervals. The primary endpoint was PSA response according to Prostate Cancer Clinical Trial Working Group criteria defined as a greater than 50% PSA decline from baseline and toxicity according to CTCAE. Additional primary endpoints were imaging responses (as measured by bone scan, CT, PSMA, and FDG PET/CT) and quality of life (assessed with the EORTC-Q30 and Brief Pain Inventory-Short Form questionnaires), all measured up to 3 months post completion of treatment. This trial is registered with the Australian New Zealand Clinical Trials Registry, number 12615000912583.
Between Aug 26, 2015, and Dec 8, 2016, 43 men were screened to identify 30 patients eligible for treatment. 26 (87%) had received at least one line of previous chemotherapy (80% docetaxel and 47% cabazitaxel) and 25 (83%) received prior abiraterone acetate, enzalutamide, or both. The mean administered radioactivity was 7·5 GBq per cycle. 17 (57%) of 30 patients (95% CI 37–75) achieved a PSA decline of 50% or more. There were no treatment-related deaths. The most common toxic effects related to [177Lu]-PSMA-617 were grade 1 dry mouth recorded in 26 (87%) patients, grade 1 and 2 transient nausea in 15 (50%), and G1–2 fatigue in 15 (50%). Grade 3 or 4 thrombocytopenia possibly attributed to [177Lu]-PSMA-617 occurred in four (13%) patients. Objective response in nodal or visceral disease was reported in 14 (82%) of 17 patients with measurable disease. Clinically meaningful improvements in pain severity and interference scores were recorded at all timepoints. 11 (37%) patients experienced a ten point or more improvement in global health score by the second cycle of treatment.
Our findings show that radionuclide treatment with [177Lu]-PSMA-617 has high response rates, low toxic effects, and reduction of pain in men with metastatic castration-resistant prostate cancer who have progressed after conventional treatments. This evidence supports the need for randomised controlled trials to further assess efficacy compared with current standards of care.
None.</description><identifier>ISSN: 1470-2045</identifier><identifier>EISSN: 1474-5488</identifier><identifier>DOI: 10.1016/S1470-2045(18)30198-0</identifier><identifier>PMID: 29752180</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Acetic acid ; Aged ; Androgens ; Bone imaging ; Bone tumors ; Cancer therapies ; Castration ; Chemotherapy ; Clinical trials ; Computed tomography ; Dipeptides - administration & dosage ; Dipeptides - adverse effects ; Disease Progression ; Fatigue ; Fractures ; Health Status ; Heterocyclic Compounds, 1-Ring - administration & dosage ; Heterocyclic Compounds, 1-Ring - adverse effects ; Humans ; Intravenous administration ; Kallikreins - blood ; Liver ; Lutetium - administration & dosage ; Lutetium - adverse effects ; Male ; Medical research ; Metastases ; Metastasis ; Nausea ; Neoplasm Metastasis ; Pain ; Patients ; Positron emission tomography ; Prospective Studies ; Prostate cancer ; Prostate-Specific Antigen - blood ; Prostatic Neoplasms, Castration-Resistant - blood ; Prostatic Neoplasms, Castration-Resistant - diagnostic imaging ; Prostatic Neoplasms, Castration-Resistant - pathology ; Prostatic Neoplasms, Castration-Resistant - radiotherapy ; Quality of Life ; Radioactivity ; Radioisotopes - administration & dosage ; Radioisotopes - adverse effects ; Radiopharmaceuticals - administration & dosage ; Radiopharmaceuticals - adverse effects ; Solid tumors ; Studies ; Thrombocytopenia ; Time Factors ; Toxicity ; Treatment Outcome ; Tumors ; Victoria</subject><ispartof>The lancet oncology, 2018-06, Vol.19 (6), p.825-833</ispartof><rights>2018 Elsevier Ltd</rights><rights>Copyright © 2018 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited Jun 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445t-253ed80e87ca04eb7ff68df7a216affa9f31d5907c5420441ff7cfa2cb09e33d3</citedby><cites>FETCH-LOGICAL-c445t-253ed80e87ca04eb7ff68df7a216affa9f31d5907c5420441ff7cfa2cb09e33d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29752180$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hofman, Michael S</creatorcontrib><creatorcontrib>Violet, John</creatorcontrib><creatorcontrib>Hicks, Rodney J</creatorcontrib><creatorcontrib>Ferdinandus, Justin</creatorcontrib><creatorcontrib>Thang, Sue Ping</creatorcontrib><creatorcontrib>Akhurst, Tim</creatorcontrib><creatorcontrib>Iravani, Amir</creatorcontrib><creatorcontrib>Kong, Grace</creatorcontrib><creatorcontrib>Ravi Kumar, Aravind</creatorcontrib><creatorcontrib>Murphy, Declan G</creatorcontrib><creatorcontrib>Eu, Peter</creatorcontrib><creatorcontrib>Jackson, Price</creatorcontrib><creatorcontrib>Scalzo, Mark</creatorcontrib><creatorcontrib>Williams, Scott G</creatorcontrib><creatorcontrib>Sandhu, Shahneen</creatorcontrib><title>[177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study</title><title>The lancet oncology</title><addtitle>Lancet Oncol</addtitle><description>Progressive metastatic castration-resistant prostate cancer is a highly lethal disorder and new effective therapeutic agents that improve patient outcomes are urgently needed. Lutetium-177 [177Lu]-PSMA-617, a radiolabelled small molecule, binds with high affinity to prostate-specific membrane antigen (PSMA) enabling beta particle therapy targeted to metastatic castration-resistant prostate cancer. We aimed to investigate the safety, efficacy, and effect on quality of life of [177Lu]-PSMA-617 in men with metastatic castration-resistant prostate cancer who progressed after standard treatments.
In this single-arm, single-centre, phase 2 trial, we recruited men (aged 18 years and older) with metastatic castration-resistant prostate cancer and progressive disease after standard treatments, including taxane-based chemotherapy and second-generation anti-androgens, from the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. Patients underwent a screening PSMA and FDG-PET/CT to confirm high PSMA-expression. Eligible patients had progressive disease defined by imaging (according to Response Evaluation Criteria In Solid Tumours [RECIST] or bone scan) or new pain in an area of radiographically evident disease, and were required to have an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or lower. Eligible patients received up to four cycles of intravenous [177Lu]-PSMA-617, at six weekly intervals. The primary endpoint was PSA response according to Prostate Cancer Clinical Trial Working Group criteria defined as a greater than 50% PSA decline from baseline and toxicity according to CTCAE. Additional primary endpoints were imaging responses (as measured by bone scan, CT, PSMA, and FDG PET/CT) and quality of life (assessed with the EORTC-Q30 and Brief Pain Inventory-Short Form questionnaires), all measured up to 3 months post completion of treatment. This trial is registered with the Australian New Zealand Clinical Trials Registry, number 12615000912583.
Between Aug 26, 2015, and Dec 8, 2016, 43 men were screened to identify 30 patients eligible for treatment. 26 (87%) had received at least one line of previous chemotherapy (80% docetaxel and 47% cabazitaxel) and 25 (83%) received prior abiraterone acetate, enzalutamide, or both. The mean administered radioactivity was 7·5 GBq per cycle. 17 (57%) of 30 patients (95% CI 37–75) achieved a PSA decline of 50% or more. There were no treatment-related deaths. The most common toxic effects related to [177Lu]-PSMA-617 were grade 1 dry mouth recorded in 26 (87%) patients, grade 1 and 2 transient nausea in 15 (50%), and G1–2 fatigue in 15 (50%). Grade 3 or 4 thrombocytopenia possibly attributed to [177Lu]-PSMA-617 occurred in four (13%) patients. Objective response in nodal or visceral disease was reported in 14 (82%) of 17 patients with measurable disease. Clinically meaningful improvements in pain severity and interference scores were recorded at all timepoints. 11 (37%) patients experienced a ten point or more improvement in global health score by the second cycle of treatment.
Our findings show that radionuclide treatment with [177Lu]-PSMA-617 has high response rates, low toxic effects, and reduction of pain in men with metastatic castration-resistant prostate cancer who have progressed after conventional treatments. This evidence supports the need for randomised controlled trials to further assess efficacy compared with current standards of care.
None.</description><subject>Acetic acid</subject><subject>Aged</subject><subject>Androgens</subject><subject>Bone imaging</subject><subject>Bone tumors</subject><subject>Cancer therapies</subject><subject>Castration</subject><subject>Chemotherapy</subject><subject>Clinical trials</subject><subject>Computed tomography</subject><subject>Dipeptides - administration & dosage</subject><subject>Dipeptides - adverse effects</subject><subject>Disease Progression</subject><subject>Fatigue</subject><subject>Fractures</subject><subject>Health Status</subject><subject>Heterocyclic Compounds, 1-Ring - administration & dosage</subject><subject>Heterocyclic Compounds, 1-Ring - adverse effects</subject><subject>Humans</subject><subject>Intravenous administration</subject><subject>Kallikreins - blood</subject><subject>Liver</subject><subject>Lutetium - administration & dosage</subject><subject>Lutetium - adverse effects</subject><subject>Male</subject><subject>Medical research</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Nausea</subject><subject>Neoplasm Metastasis</subject><subject>Pain</subject><subject>Patients</subject><subject>Positron emission tomography</subject><subject>Prospective Studies</subject><subject>Prostate cancer</subject><subject>Prostate-Specific Antigen - blood</subject><subject>Prostatic Neoplasms, Castration-Resistant - blood</subject><subject>Prostatic Neoplasms, Castration-Resistant - diagnostic imaging</subject><subject>Prostatic Neoplasms, Castration-Resistant - pathology</subject><subject>Prostatic Neoplasms, Castration-Resistant - radiotherapy</subject><subject>Quality of Life</subject><subject>Radioactivity</subject><subject>Radioisotopes - administration & dosage</subject><subject>Radioisotopes - adverse effects</subject><subject>Radiopharmaceuticals - administration & dosage</subject><subject>Radiopharmaceuticals - adverse effects</subject><subject>Solid tumors</subject><subject>Studies</subject><subject>Thrombocytopenia</subject><subject>Time Factors</subject><subject>Toxicity</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><subject>Victoria</subject><issn>1470-2045</issn><issn>1474-5488</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNqFUV1vFCEUnRgb-6E_QUPiS5sUBQYGxhfTNFWbrNGk-mQMYeFiaXZmVmBs-nv8o97dbX3tE4d7zzmXy2mal5y94Yx3b6-41IwKJtUxNyct472h7ElzgGVJlTTm6RbvKPvNYSk3jHHNmXrW7IteK8ENO2j-_uBaL-af9OvV5zPacU2yC2kaZ79KAUjN4OoAYyVpJGtXE8JCblO9JgNUVyqWPPEIMqJppBlKwioK1nnatAG7o4dMjhfzZgZaJrc6eUccKWn8tQLq0TPD6cPV5eGUrK9dASJIqXO4e97sRbcq8OL-PGq-f7j4dv6JLr58vDw_W1AvpapUqBaCYWC0d0zCUsfYmRC1E7xzMbo-tjyonmmvJH6K5DFqH53wS9ZD24b2qHm988Wn_56hVHszzXnEkRb5uhdCdgJZasfyuGDJEO06p8HlO8uZ3URjt9FsJMpyY7fRWIa6V_fu83KA8F_1kAUS3u8IgDv-SZBt8fjfHkLK4KsNU3pkxD82Tp8j</recordid><startdate>201806</startdate><enddate>201806</enddate><creator>Hofman, Michael S</creator><creator>Violet, John</creator><creator>Hicks, Rodney J</creator><creator>Ferdinandus, Justin</creator><creator>Thang, Sue Ping</creator><creator>Akhurst, Tim</creator><creator>Iravani, Amir</creator><creator>Kong, Grace</creator><creator>Ravi Kumar, Aravind</creator><creator>Murphy, Declan G</creator><creator>Eu, Peter</creator><creator>Jackson, Price</creator><creator>Scalzo, Mark</creator><creator>Williams, Scott G</creator><creator>Sandhu, Shahneen</creator><general>Elsevier Ltd</general><general>Elsevier Limited</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>0TZ</scope><scope>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8C2</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>201806</creationdate><title>[177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study</title><author>Hofman, Michael S ; Violet, John ; Hicks, Rodney J ; Ferdinandus, Justin ; Thang, Sue Ping ; Akhurst, Tim ; Iravani, Amir ; Kong, Grace ; Ravi Kumar, Aravind ; Murphy, Declan G ; Eu, Peter ; Jackson, Price ; Scalzo, Mark ; Williams, Scott G ; Sandhu, Shahneen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445t-253ed80e87ca04eb7ff68df7a216affa9f31d5907c5420441ff7cfa2cb09e33d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Acetic acid</topic><topic>Aged</topic><topic>Androgens</topic><topic>Bone imaging</topic><topic>Bone tumors</topic><topic>Cancer therapies</topic><topic>Castration</topic><topic>Chemotherapy</topic><topic>Clinical trials</topic><topic>Computed tomography</topic><topic>Dipeptides - 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pathology</topic><topic>Prostatic Neoplasms, Castration-Resistant - radiotherapy</topic><topic>Quality of Life</topic><topic>Radioactivity</topic><topic>Radioisotopes - administration & dosage</topic><topic>Radioisotopes - adverse effects</topic><topic>Radiopharmaceuticals - administration & dosage</topic><topic>Radiopharmaceuticals - adverse effects</topic><topic>Solid tumors</topic><topic>Studies</topic><topic>Thrombocytopenia</topic><topic>Time Factors</topic><topic>Toxicity</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><topic>Victoria</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hofman, Michael S</creatorcontrib><creatorcontrib>Violet, John</creatorcontrib><creatorcontrib>Hicks, Rodney J</creatorcontrib><creatorcontrib>Ferdinandus, Justin</creatorcontrib><creatorcontrib>Thang, Sue Ping</creatorcontrib><creatorcontrib>Akhurst, Tim</creatorcontrib><creatorcontrib>Iravani, Amir</creatorcontrib><creatorcontrib>Kong, Grace</creatorcontrib><creatorcontrib>Ravi Kumar, Aravind</creatorcontrib><creatorcontrib>Murphy, Declan G</creatorcontrib><creatorcontrib>Eu, Peter</creatorcontrib><creatorcontrib>Jackson, Price</creatorcontrib><creatorcontrib>Scalzo, Mark</creatorcontrib><creatorcontrib>Williams, Scott G</creatorcontrib><creatorcontrib>Sandhu, Shahneen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Pharma and Biotech Premium PRO</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database (Proquest)</collection><collection>Lancet Titles</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Nursing & Allied Health Premium</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><jtitle>The lancet oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hofman, Michael S</au><au>Violet, John</au><au>Hicks, Rodney J</au><au>Ferdinandus, Justin</au><au>Thang, Sue Ping</au><au>Akhurst, Tim</au><au>Iravani, Amir</au><au>Kong, Grace</au><au>Ravi Kumar, Aravind</au><au>Murphy, Declan G</au><au>Eu, Peter</au><au>Jackson, Price</au><au>Scalzo, Mark</au><au>Williams, Scott G</au><au>Sandhu, Shahneen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>[177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study</atitle><jtitle>The lancet oncology</jtitle><addtitle>Lancet Oncol</addtitle><date>2018-06</date><risdate>2018</risdate><volume>19</volume><issue>6</issue><spage>825</spage><epage>833</epage><pages>825-833</pages><issn>1470-2045</issn><eissn>1474-5488</eissn><abstract>Progressive metastatic castration-resistant prostate cancer is a highly lethal disorder and new effective therapeutic agents that improve patient outcomes are urgently needed. Lutetium-177 [177Lu]-PSMA-617, a radiolabelled small molecule, binds with high affinity to prostate-specific membrane antigen (PSMA) enabling beta particle therapy targeted to metastatic castration-resistant prostate cancer. We aimed to investigate the safety, efficacy, and effect on quality of life of [177Lu]-PSMA-617 in men with metastatic castration-resistant prostate cancer who progressed after standard treatments.
In this single-arm, single-centre, phase 2 trial, we recruited men (aged 18 years and older) with metastatic castration-resistant prostate cancer and progressive disease after standard treatments, including taxane-based chemotherapy and second-generation anti-androgens, from the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. Patients underwent a screening PSMA and FDG-PET/CT to confirm high PSMA-expression. Eligible patients had progressive disease defined by imaging (according to Response Evaluation Criteria In Solid Tumours [RECIST] or bone scan) or new pain in an area of radiographically evident disease, and were required to have an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or lower. Eligible patients received up to four cycles of intravenous [177Lu]-PSMA-617, at six weekly intervals. The primary endpoint was PSA response according to Prostate Cancer Clinical Trial Working Group criteria defined as a greater than 50% PSA decline from baseline and toxicity according to CTCAE. Additional primary endpoints were imaging responses (as measured by bone scan, CT, PSMA, and FDG PET/CT) and quality of life (assessed with the EORTC-Q30 and Brief Pain Inventory-Short Form questionnaires), all measured up to 3 months post completion of treatment. This trial is registered with the Australian New Zealand Clinical Trials Registry, number 12615000912583.
Between Aug 26, 2015, and Dec 8, 2016, 43 men were screened to identify 30 patients eligible for treatment. 26 (87%) had received at least one line of previous chemotherapy (80% docetaxel and 47% cabazitaxel) and 25 (83%) received prior abiraterone acetate, enzalutamide, or both. The mean administered radioactivity was 7·5 GBq per cycle. 17 (57%) of 30 patients (95% CI 37–75) achieved a PSA decline of 50% or more. There were no treatment-related deaths. The most common toxic effects related to [177Lu]-PSMA-617 were grade 1 dry mouth recorded in 26 (87%) patients, grade 1 and 2 transient nausea in 15 (50%), and G1–2 fatigue in 15 (50%). Grade 3 or 4 thrombocytopenia possibly attributed to [177Lu]-PSMA-617 occurred in four (13%) patients. Objective response in nodal or visceral disease was reported in 14 (82%) of 17 patients with measurable disease. Clinically meaningful improvements in pain severity and interference scores were recorded at all timepoints. 11 (37%) patients experienced a ten point or more improvement in global health score by the second cycle of treatment.
Our findings show that radionuclide treatment with [177Lu]-PSMA-617 has high response rates, low toxic effects, and reduction of pain in men with metastatic castration-resistant prostate cancer who have progressed after conventional treatments. This evidence supports the need for randomised controlled trials to further assess efficacy compared with current standards of care.
None.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>29752180</pmid><doi>10.1016/S1470-2045(18)30198-0</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1470-2045 |
| ispartof | The lancet oncology, 2018-06, Vol.19 (6), p.825-833 |
| issn | 1470-2045 1474-5488 |
| language | eng |
| recordid | cdi_proquest_journals_2047922462 |
| source | ScienceDirect Freedom Collection 2022-2024 |
| subjects | Acetic acid Aged Androgens Bone imaging Bone tumors Cancer therapies Castration Chemotherapy Clinical trials Computed tomography Dipeptides - administration & dosage Dipeptides - adverse effects Disease Progression Fatigue Fractures Health Status Heterocyclic Compounds, 1-Ring - administration & dosage Heterocyclic Compounds, 1-Ring - adverse effects Humans Intravenous administration Kallikreins - blood Liver Lutetium - administration & dosage Lutetium - adverse effects Male Medical research Metastases Metastasis Nausea Neoplasm Metastasis Pain Patients Positron emission tomography Prospective Studies Prostate cancer Prostate-Specific Antigen - blood Prostatic Neoplasms, Castration-Resistant - blood Prostatic Neoplasms, Castration-Resistant - diagnostic imaging Prostatic Neoplasms, Castration-Resistant - pathology Prostatic Neoplasms, Castration-Resistant - radiotherapy Quality of Life Radioactivity Radioisotopes - administration & dosage Radioisotopes - adverse effects Radiopharmaceuticals - administration & dosage Radiopharmaceuticals - adverse effects Solid tumors Studies Thrombocytopenia Time Factors Toxicity Treatment Outcome Tumors Victoria |
| title | [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-23T00%3A25%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=%5B177Lu%5D-PSMA-617%20radionuclide%20treatment%20in%20patients%20with%20metastatic%20castration-resistant%20prostate%20cancer%20(LuPSMA%20trial):%20a%20single-centre,%20single-arm,%20phase%202%20study&rft.jtitle=The%20lancet%20oncology&rft.au=Hofman,%20Michael%20S&rft.date=2018-06&rft.volume=19&rft.issue=6&rft.spage=825&rft.epage=833&rft.pages=825-833&rft.issn=1470-2045&rft.eissn=1474-5488&rft_id=info:doi/10.1016/S1470-2045(18)30198-0&rft_dat=%3Cproquest_cross%3E2047922462%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c445t-253ed80e87ca04eb7ff68df7a216affa9f31d5907c5420441ff7cfa2cb09e33d3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2047922462&rft_id=info:pmid/29752180&rfr_iscdi=true |