Combination gemcitabine/cisplatin therapy and ERCC1 expression for resected pancreatic adenocarcinoma: Results of a Phase II prospective trial
Background Standard adjuvant treatment for pancreatic adenocarcinoma (PDAC) is gemcitabine [Gem(CONKO‐001: Gem vs. placebo DFS:13.4 vs. 6.7 mo; P
Gespeichert in:
| Veröffentlicht in: | Journal of surgical oncology 2016-09, Vol.114 (3), p.336-341 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 341 |
|---|---|
| container_issue | 3 |
| container_start_page | 336 |
| container_title | Journal of surgical oncology |
| container_volume | 114 |
| creator | Postlewait, Lauren M. Ethun, Cecilia G. Kooby, David A. Sarmiento, Juan M. Chen, Zhengjia Staley III, Charles A. Brutcher, Edith Adsay, Volkan El-Rayes, Bassel Maithel, Shishir K. |
| description | Background
Standard adjuvant treatment for pancreatic adenocarcinoma (PDAC) is gemcitabine [Gem(CONKO‐001: Gem vs. placebo DFS:13.4 vs. 6.7 mo; P |
| doi_str_mv | 10.1002/jso.24317 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_1812875755</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>4154477041</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5317-c9010b12dc6e93535e48408d511cf8f0c171fd083c4d8fe6dd585a27b14c44ac3</originalsourceid><addsrcrecordid>eNp1kMFu1DAQhi1ERZfCgRdAljj1kK4d27HDDUWlbFu11QICcbG89oR6SeJgZ6H7Ejxz3W7bG6fx2N__z_hH6A0lR5SQcr5O4ajkjMpnaEZJXRU1qdVzNMtvZcFlTfbRy5TWhJC6rvgLtF9KQShjaob-NaFf-cFMPgz4J_TWTyb3MLc-jV2-HvB0DdGMW2wGh4-XTUMx3IwRUrqTtCHifAY7gcOjGWyELLLYOBiCNdH6IfTmPV5C2nRTwqHFBl9dmwR4scBjDGnMWv8H8BS96V6hvdZ0CV4_1AP09ePxl-ZTcX55smg-nBdW5G8WtiaUrGjpbAU1E0wAV5woJyi1rWqJpZK2jihmuVMtVM4JJUwpV5Rbzo1lB-jdzjdv8HsDadLrsIlDHqmpoqWSQgqRqcMdZfOeKUKrx-h7E7eaEn2XvM7J6_vkM_v2wXGz6sE9kY9RZ2C-A_76Drb_d9Knny8fLYudwqcJbp4UJv7SlWRS6G8XJ5o2Z5Isf3zXV-wWhw6eJA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1812875755</pqid></control><display><type>article</type><title>Combination gemcitabine/cisplatin therapy and ERCC1 expression for resected pancreatic adenocarcinoma: Results of a Phase II prospective trial</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Postlewait, Lauren M. ; Ethun, Cecilia G. ; Kooby, David A. ; Sarmiento, Juan M. ; Chen, Zhengjia ; Staley III, Charles A. ; Brutcher, Edith ; Adsay, Volkan ; El-Rayes, Bassel ; Maithel, Shishir K.</creator><creatorcontrib>Postlewait, Lauren M. ; Ethun, Cecilia G. ; Kooby, David A. ; Sarmiento, Juan M. ; Chen, Zhengjia ; Staley III, Charles A. ; Brutcher, Edith ; Adsay, Volkan ; El-Rayes, Bassel ; Maithel, Shishir K.</creatorcontrib><description>Background
Standard adjuvant treatment for pancreatic adenocarcinoma (PDAC) is gemcitabine [Gem(CONKO‐001: Gem vs. placebo DFS:13.4 vs. 6.7 mo; P < 0.001; OS:22.8 vs. 20.2 mo; P = 0.01)]. Addition of cisplatin (Cis) to Gem has resulted in increased PFS for advanced and metastatic disease, which may be predicted by low expression of excision repair cross‐complementing group–1 (ERCC1), the key enzyme in nucleotide excision repair. This Phase II prospective trial assesses outcomes of patients treated with adjuvant Gem/Cis, stratifying results by tumor ERCC1 expression.
Methods
Patients with resected PDAC were enrolled (2010–2013) and received Gem(1,000 mg/m2)/Cis(50 mg/m2). Tumor ERCC1 expression was evaluated by immunohistochemistry and dichotomized into low or high expression. Primary outcomes were recurrence‐free and overall survival (RFS/OS).
Results
Of 22 pts, 16(73%) were Stage IIB, 5(23%) Stage IIA, and 1(4%) Stage IA. Grade 3/4 toxicity occurred in 13 pts (59%); neutropenia was most common (n = 9;41%). Median follow‐up was 37.5 months. Median RFS was 16.7 mo; OS was 35.5 mo. Low ERCC1 (n = 15;75%) compared to high ERCC1 (n = 5;25%) was not associated with improved RFS (12.4 vs. 16.7 mo; P = 0.68) or OS (Median not reached vs. 21.6 mo; P = 0.22).
Conclusions
Adjuvant Gem/Cis is feasible in patients with resected pancreatic adenocarcinoma. RFS and OS for Gem/Cis appear promising compared to historic control. Tumor ERCC1 expression can be reliably evaluated, and low expression is present in most patients. J. Surg. Oncol. 2016;114:336–341. © 2016 Wiley Periodicals, Inc.</description><identifier>ISSN: 0022-4790</identifier><identifier>EISSN: 1096-9098</identifier><identifier>DOI: 10.1002/jso.24317</identifier><identifier>PMID: 27501338</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Adenocarcinoma - metabolism ; Adenocarcinoma - mortality ; Adenocarcinoma - therapy ; adjuvant chemotherapy ; Aged ; Antineoplastic Agents - toxicity ; Biomarkers - metabolism ; Chemotherapy, Adjuvant ; Cisplatin - therapeutic use ; Deoxycytidine - analogs & derivatives ; Deoxycytidine - therapeutic use ; DNA-Binding Proteins - metabolism ; Drug Therapy, Combination ; Endonucleases - metabolism ; ERCC1 ; Feasibility Studies ; Female ; Humans ; Male ; Middle Aged ; Pancreatectomy ; pancreatic ductal adenocarcinoma ; Pancreatic Neoplasms - metabolism ; Pancreatic Neoplasms - mortality ; Pancreatic Neoplasms - therapy ; predictive markers ; Predictive Value of Tests ; Prospective Studies ; recurrence ; survival ; Treatment Outcome</subject><ispartof>Journal of surgical oncology, 2016-09, Vol.114 (3), p.336-341</ispartof><rights>2016 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5317-c9010b12dc6e93535e48408d511cf8f0c171fd083c4d8fe6dd585a27b14c44ac3</citedby><cites>FETCH-LOGICAL-c5317-c9010b12dc6e93535e48408d511cf8f0c171fd083c4d8fe6dd585a27b14c44ac3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjso.24317$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjso.24317$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27501338$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Postlewait, Lauren M.</creatorcontrib><creatorcontrib>Ethun, Cecilia G.</creatorcontrib><creatorcontrib>Kooby, David A.</creatorcontrib><creatorcontrib>Sarmiento, Juan M.</creatorcontrib><creatorcontrib>Chen, Zhengjia</creatorcontrib><creatorcontrib>Staley III, Charles A.</creatorcontrib><creatorcontrib>Brutcher, Edith</creatorcontrib><creatorcontrib>Adsay, Volkan</creatorcontrib><creatorcontrib>El-Rayes, Bassel</creatorcontrib><creatorcontrib>Maithel, Shishir K.</creatorcontrib><title>Combination gemcitabine/cisplatin therapy and ERCC1 expression for resected pancreatic adenocarcinoma: Results of a Phase II prospective trial</title><title>Journal of surgical oncology</title><addtitle>J. Surg. Oncol</addtitle><description>Background
Standard adjuvant treatment for pancreatic adenocarcinoma (PDAC) is gemcitabine [Gem(CONKO‐001: Gem vs. placebo DFS:13.4 vs. 6.7 mo; P < 0.001; OS:22.8 vs. 20.2 mo; P = 0.01)]. Addition of cisplatin (Cis) to Gem has resulted in increased PFS for advanced and metastatic disease, which may be predicted by low expression of excision repair cross‐complementing group–1 (ERCC1), the key enzyme in nucleotide excision repair. This Phase II prospective trial assesses outcomes of patients treated with adjuvant Gem/Cis, stratifying results by tumor ERCC1 expression.
Methods
Patients with resected PDAC were enrolled (2010–2013) and received Gem(1,000 mg/m2)/Cis(50 mg/m2). Tumor ERCC1 expression was evaluated by immunohistochemistry and dichotomized into low or high expression. Primary outcomes were recurrence‐free and overall survival (RFS/OS).
Results
Of 22 pts, 16(73%) were Stage IIB, 5(23%) Stage IIA, and 1(4%) Stage IA. Grade 3/4 toxicity occurred in 13 pts (59%); neutropenia was most common (n = 9;41%). Median follow‐up was 37.5 months. Median RFS was 16.7 mo; OS was 35.5 mo. Low ERCC1 (n = 15;75%) compared to high ERCC1 (n = 5;25%) was not associated with improved RFS (12.4 vs. 16.7 mo; P = 0.68) or OS (Median not reached vs. 21.6 mo; P = 0.22).
Conclusions
Adjuvant Gem/Cis is feasible in patients with resected pancreatic adenocarcinoma. RFS and OS for Gem/Cis appear promising compared to historic control. Tumor ERCC1 expression can be reliably evaluated, and low expression is present in most patients. J. Surg. Oncol. 2016;114:336–341. © 2016 Wiley Periodicals, Inc.</description><subject>Adenocarcinoma - metabolism</subject><subject>Adenocarcinoma - mortality</subject><subject>Adenocarcinoma - therapy</subject><subject>adjuvant chemotherapy</subject><subject>Aged</subject><subject>Antineoplastic Agents - toxicity</subject><subject>Biomarkers - metabolism</subject><subject>Chemotherapy, Adjuvant</subject><subject>Cisplatin - therapeutic use</subject><subject>Deoxycytidine - analogs & derivatives</subject><subject>Deoxycytidine - therapeutic use</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Drug Therapy, Combination</subject><subject>Endonucleases - metabolism</subject><subject>ERCC1</subject><subject>Feasibility Studies</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Pancreatectomy</subject><subject>pancreatic ductal adenocarcinoma</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Pancreatic Neoplasms - mortality</subject><subject>Pancreatic Neoplasms - therapy</subject><subject>predictive markers</subject><subject>Predictive Value of Tests</subject><subject>Prospective Studies</subject><subject>recurrence</subject><subject>survival</subject><subject>Treatment Outcome</subject><issn>0022-4790</issn><issn>1096-9098</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMFu1DAQhi1ERZfCgRdAljj1kK4d27HDDUWlbFu11QICcbG89oR6SeJgZ6H7Ejxz3W7bG6fx2N__z_hH6A0lR5SQcr5O4ajkjMpnaEZJXRU1qdVzNMtvZcFlTfbRy5TWhJC6rvgLtF9KQShjaob-NaFf-cFMPgz4J_TWTyb3MLc-jV2-HvB0DdGMW2wGh4-XTUMx3IwRUrqTtCHifAY7gcOjGWyELLLYOBiCNdH6IfTmPV5C2nRTwqHFBl9dmwR4scBjDGnMWv8H8BS96V6hvdZ0CV4_1AP09ePxl-ZTcX55smg-nBdW5G8WtiaUrGjpbAU1E0wAV5woJyi1rWqJpZK2jihmuVMtVM4JJUwpV5Rbzo1lB-jdzjdv8HsDadLrsIlDHqmpoqWSQgqRqcMdZfOeKUKrx-h7E7eaEn2XvM7J6_vkM_v2wXGz6sE9kY9RZ2C-A_76Drb_d9Knny8fLYudwqcJbp4UJv7SlWRS6G8XJ5o2Z5Isf3zXV-wWhw6eJA</recordid><startdate>20160901</startdate><enddate>20160901</enddate><creator>Postlewait, Lauren M.</creator><creator>Ethun, Cecilia G.</creator><creator>Kooby, David A.</creator><creator>Sarmiento, Juan M.</creator><creator>Chen, Zhengjia</creator><creator>Staley III, Charles A.</creator><creator>Brutcher, Edith</creator><creator>Adsay, Volkan</creator><creator>El-Rayes, Bassel</creator><creator>Maithel, Shishir K.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>K9.</scope></search><sort><creationdate>20160901</creationdate><title>Combination gemcitabine/cisplatin therapy and ERCC1 expression for resected pancreatic adenocarcinoma: Results of a Phase II prospective trial</title><author>Postlewait, Lauren M. ; Ethun, Cecilia G. ; Kooby, David A. ; Sarmiento, Juan M. ; Chen, Zhengjia ; Staley III, Charles A. ; Brutcher, Edith ; Adsay, Volkan ; El-Rayes, Bassel ; Maithel, Shishir K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5317-c9010b12dc6e93535e48408d511cf8f0c171fd083c4d8fe6dd585a27b14c44ac3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adenocarcinoma - metabolism</topic><topic>Adenocarcinoma - mortality</topic><topic>Adenocarcinoma - therapy</topic><topic>adjuvant chemotherapy</topic><topic>Aged</topic><topic>Antineoplastic Agents - toxicity</topic><topic>Biomarkers - metabolism</topic><topic>Chemotherapy, Adjuvant</topic><topic>Cisplatin - therapeutic use</topic><topic>Deoxycytidine - analogs & derivatives</topic><topic>Deoxycytidine - therapeutic use</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Drug Therapy, Combination</topic><topic>Endonucleases - metabolism</topic><topic>ERCC1</topic><topic>Feasibility Studies</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Pancreatectomy</topic><topic>pancreatic ductal adenocarcinoma</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Pancreatic Neoplasms - mortality</topic><topic>Pancreatic Neoplasms - therapy</topic><topic>predictive markers</topic><topic>Predictive Value of Tests</topic><topic>Prospective Studies</topic><topic>recurrence</topic><topic>survival</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Postlewait, Lauren M.</creatorcontrib><creatorcontrib>Ethun, Cecilia G.</creatorcontrib><creatorcontrib>Kooby, David A.</creatorcontrib><creatorcontrib>Sarmiento, Juan M.</creatorcontrib><creatorcontrib>Chen, Zhengjia</creatorcontrib><creatorcontrib>Staley III, Charles A.</creatorcontrib><creatorcontrib>Brutcher, Edith</creatorcontrib><creatorcontrib>Adsay, Volkan</creatorcontrib><creatorcontrib>El-Rayes, Bassel</creatorcontrib><creatorcontrib>Maithel, Shishir K.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><jtitle>Journal of surgical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Postlewait, Lauren M.</au><au>Ethun, Cecilia G.</au><au>Kooby, David A.</au><au>Sarmiento, Juan M.</au><au>Chen, Zhengjia</au><au>Staley III, Charles A.</au><au>Brutcher, Edith</au><au>Adsay, Volkan</au><au>El-Rayes, Bassel</au><au>Maithel, Shishir K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Combination gemcitabine/cisplatin therapy and ERCC1 expression for resected pancreatic adenocarcinoma: Results of a Phase II prospective trial</atitle><jtitle>Journal of surgical oncology</jtitle><addtitle>J. Surg. Oncol</addtitle><date>2016-09-01</date><risdate>2016</risdate><volume>114</volume><issue>3</issue><spage>336</spage><epage>341</epage><pages>336-341</pages><issn>0022-4790</issn><eissn>1096-9098</eissn><abstract>Background
Standard adjuvant treatment for pancreatic adenocarcinoma (PDAC) is gemcitabine [Gem(CONKO‐001: Gem vs. placebo DFS:13.4 vs. 6.7 mo; P < 0.001; OS:22.8 vs. 20.2 mo; P = 0.01)]. Addition of cisplatin (Cis) to Gem has resulted in increased PFS for advanced and metastatic disease, which may be predicted by low expression of excision repair cross‐complementing group–1 (ERCC1), the key enzyme in nucleotide excision repair. This Phase II prospective trial assesses outcomes of patients treated with adjuvant Gem/Cis, stratifying results by tumor ERCC1 expression.
Methods
Patients with resected PDAC were enrolled (2010–2013) and received Gem(1,000 mg/m2)/Cis(50 mg/m2). Tumor ERCC1 expression was evaluated by immunohistochemistry and dichotomized into low or high expression. Primary outcomes were recurrence‐free and overall survival (RFS/OS).
Results
Of 22 pts, 16(73%) were Stage IIB, 5(23%) Stage IIA, and 1(4%) Stage IA. Grade 3/4 toxicity occurred in 13 pts (59%); neutropenia was most common (n = 9;41%). Median follow‐up was 37.5 months. Median RFS was 16.7 mo; OS was 35.5 mo. Low ERCC1 (n = 15;75%) compared to high ERCC1 (n = 5;25%) was not associated with improved RFS (12.4 vs. 16.7 mo; P = 0.68) or OS (Median not reached vs. 21.6 mo; P = 0.22).
Conclusions
Adjuvant Gem/Cis is feasible in patients with resected pancreatic adenocarcinoma. RFS and OS for Gem/Cis appear promising compared to historic control. Tumor ERCC1 expression can be reliably evaluated, and low expression is present in most patients. J. Surg. Oncol. 2016;114:336–341. © 2016 Wiley Periodicals, Inc.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>27501338</pmid><doi>10.1002/jso.24317</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-4790 |
| ispartof | Journal of surgical oncology, 2016-09, Vol.114 (3), p.336-341 |
| issn | 0022-4790 1096-9098 |
| language | eng |
| recordid | cdi_proquest_journals_1812875755 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adenocarcinoma - metabolism Adenocarcinoma - mortality Adenocarcinoma - therapy adjuvant chemotherapy Aged Antineoplastic Agents - toxicity Biomarkers - metabolism Chemotherapy, Adjuvant Cisplatin - therapeutic use Deoxycytidine - analogs & derivatives Deoxycytidine - therapeutic use DNA-Binding Proteins - metabolism Drug Therapy, Combination Endonucleases - metabolism ERCC1 Feasibility Studies Female Humans Male Middle Aged Pancreatectomy pancreatic ductal adenocarcinoma Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - mortality Pancreatic Neoplasms - therapy predictive markers Predictive Value of Tests Prospective Studies recurrence survival Treatment Outcome |
| title | Combination gemcitabine/cisplatin therapy and ERCC1 expression for resected pancreatic adenocarcinoma: Results of a Phase II prospective trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-06T14%3A11%3A56IST&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=Combination%20gemcitabine/cisplatin%20therapy%20and%20ERCC1%20expression%20for%20resected%20pancreatic%20adenocarcinoma:%20Results%20of%20a%20Phase%20II%20prospective%20trial&rft.jtitle=Journal%20of%20surgical%20oncology&rft.au=Postlewait,%20Lauren%20M.&rft.date=2016-09-01&rft.volume=114&rft.issue=3&rft.spage=336&rft.epage=341&rft.pages=336-341&rft.issn=0022-4790&rft.eissn=1096-9098&rft_id=info:doi/10.1002/jso.24317&rft_dat=%3Cproquest_cross%3E4154477041%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1812875755&rft_id=info:pmid/27501338&rfr_iscdi=true |