Scheduling nab-paclitaxel combined with gemcitabine as first-line treatment for metastatic pancreatic adenocarcinoma
Background Nab-paclitaxel plus gemcitabine (nabP+gemcitabine) offers modest survival gains for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Sequential scheduling of nabP+gemcitabine in a PDAC mouse model improved efficacy; this hypothesis was tested in a clinical trial. Methods...
Gespeichert in:
| Veröffentlicht in: | British journal of cancer 2020-06, Vol.122 (12), p.1760-1768 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1768 |
|---|---|
| container_issue | 12 |
| container_start_page | 1760 |
| container_title | British journal of cancer |
| container_volume | 122 |
| creator | Corrie, P. G. Qian, W. Basu, B. Valle, J. W. Falk, S. lwuji, C. Wasan, H. Palmer, D. Scott-Brown, M. Wadsley, J. Arif, S. Bridgewater, J. Propper, D. Gillmore, R. Gopinathan, A. Skells, R. Bundi, P. Brais, R. Dalchau, K. Bax, L. Chhabra, A. Machin, A. Dayim, A. McAdam, K. Cummins, S. Wall, L. Ellis, R. Anthoney, A. Evans, J. Ma, Y. T. Isherwood, C. Neesse, A. Tuveson, D. Jodrell, D. I. |
| description | Background
Nab-paclitaxel plus gemcitabine (nabP+gemcitabine) offers modest survival gains for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Sequential scheduling of nabP+gemcitabine in a PDAC mouse model improved efficacy; this hypothesis was tested in a clinical trial.
Methods
Patients with previously untreated metastatic PDAC were randomised to receive nabP+gemcitabine administered either concomitantly on the same day, or sequentially, with gemcitabine administered 24 h after nabP. The primary outcome measure was progression-free survival (PFS). Secondary outcome measures were objective response rate (ORR), overall survival (OS), safety, quality of life (QoL) and predictive biomarkers.
Results
In total, 71 patients received sequential (SEQ) and 75 concomitant (CON) treatment. Six-month PFS was 46% with SEQ and 32% with CON scheduling. Median PFS (5.6 versus 4.0 months, hazard ratio [HR] 0.67, 95% confidence interval [95% CI] 0.47–0.95,
p
= 0.022) and ORR (52% versus 31%,
p
= 0.023) favoured the SEQ arm; median OS was 10.2 versus 8.2 months (HR 0.93, 95% CI 0.65–1.33,
p
= 0.70). CTCAE Grade
≥
3 neutropaenia incidence doubled with SEQ therapy but was not detrimental to QoL. Strongly positive tumour epithelial cytidine deaminase (CDA) expression favoured benefit from SEQ therapy (PFS HR 0.31, 95% CI 0.13–0.70).
Conclusions
SEQ delivery of nabP+gemcitabine improved PFS and ORR, with manageable toxicity, but did not significantly improve OS.
Clinical trial registration
ISRCTN71070888; ClinialTrials.gov (NCT03529175). |
| doi_str_mv | 10.1038/s41416-020-0846-2 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7283477</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2411083047</sourcerecordid><originalsourceid>FETCH-LOGICAL-c470t-13ac3ced72f45ef5aaa7d79cf6e25c753c5186c83a6ec35dd4ecf90c7d621f283</originalsourceid><addsrcrecordid>eNp1UcuKFDEUDaI47egHuJGA62heVaneCDL4ggEX6jrcvkm6M1QlbZL28fem6HHUhavk3vO4Bw4hTwV_IbiaXlYttBgZl5zxSY9M3iMbMSjJxCTNfbLhnBvGt5JfkEe13vRxyyfzkFwoqQauhdqQ9gkP3p3mmPY0wY4dAefY4IefKeZlF5N39HtsB7r3C3Zg3VCoNMRSG5vXqRUPbfGp0ZALXXyD2qBFpEdIuGL9C86njFAwprzAY_IgwFz9k9v3knx5--bz1Xt2_fHdh6vX1wy14Y0JBajQOyODHnwYAMA4s8UwejmgGRQOYhpxUjB6VINz2mPYcjRulCLISV2SV2ff42m3eIc9Y4HZHktcoPy0GaL9F0nxYPf5mzVdrI3pBs9vDUr-evK12Zt8KqlntlILwSfF9coSZxaWXGvx4e6C4HYtyp6Lsr0ouxZlZdc8-zvaneJ3M50gz4TaobT35c_p_7v-AsGeomQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2411083047</pqid></control><display><type>article</type><title>Scheduling nab-paclitaxel combined with gemcitabine as first-line treatment for metastatic pancreatic adenocarcinoma</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>SpringerLink Journals - AutoHoldings</source><creator>Corrie, P. G. ; Qian, W. ; Basu, B. ; Valle, J. W. ; Falk, S. ; lwuji, C. ; Wasan, H. ; Palmer, D. ; Scott-Brown, M. ; Wadsley, J. ; Arif, S. ; Bridgewater, J. ; Propper, D. ; Gillmore, R. ; Gopinathan, A. ; Skells, R. ; Bundi, P. ; Brais, R. ; Dalchau, K. ; Bax, L. ; Chhabra, A. ; Machin, A. ; Dayim, A. ; McAdam, K. ; Cummins, S. ; Wall, L. ; Ellis, R. ; Anthoney, A. ; Evans, J. ; Ma, Y. T. ; Isherwood, C. ; Neesse, A. ; Tuveson, D. ; Jodrell, D. I.</creator><creatorcontrib>Corrie, P. G. ; Qian, W. ; Basu, B. ; Valle, J. W. ; Falk, S. ; lwuji, C. ; Wasan, H. ; Palmer, D. ; Scott-Brown, M. ; Wadsley, J. ; Arif, S. ; Bridgewater, J. ; Propper, D. ; Gillmore, R. ; Gopinathan, A. ; Skells, R. ; Bundi, P. ; Brais, R. ; Dalchau, K. ; Bax, L. ; Chhabra, A. ; Machin, A. ; Dayim, A. ; McAdam, K. ; Cummins, S. ; Wall, L. ; Ellis, R. ; Anthoney, A. ; Evans, J. ; Ma, Y. T. ; Isherwood, C. ; Neesse, A. ; Tuveson, D. ; Jodrell, D. I.</creatorcontrib><description>Background
Nab-paclitaxel plus gemcitabine (nabP+gemcitabine) offers modest survival gains for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Sequential scheduling of nabP+gemcitabine in a PDAC mouse model improved efficacy; this hypothesis was tested in a clinical trial.
Methods
Patients with previously untreated metastatic PDAC were randomised to receive nabP+gemcitabine administered either concomitantly on the same day, or sequentially, with gemcitabine administered 24 h after nabP. The primary outcome measure was progression-free survival (PFS). Secondary outcome measures were objective response rate (ORR), overall survival (OS), safety, quality of life (QoL) and predictive biomarkers.
Results
In total, 71 patients received sequential (SEQ) and 75 concomitant (CON) treatment. Six-month PFS was 46% with SEQ and 32% with CON scheduling. Median PFS (5.6 versus 4.0 months, hazard ratio [HR] 0.67, 95% confidence interval [95% CI] 0.47–0.95,
p
= 0.022) and ORR (52% versus 31%,
p
= 0.023) favoured the SEQ arm; median OS was 10.2 versus 8.2 months (HR 0.93, 95% CI 0.65–1.33,
p
= 0.70). CTCAE Grade
≥
3 neutropaenia incidence doubled with SEQ therapy but was not detrimental to QoL. Strongly positive tumour epithelial cytidine deaminase (CDA) expression favoured benefit from SEQ therapy (PFS HR 0.31, 95% CI 0.13–0.70).
Conclusions
SEQ delivery of nabP+gemcitabine improved PFS and ORR, with manageable toxicity, but did not significantly improve OS.
Clinical trial registration
ISRCTN71070888; ClinialTrials.gov (NCT03529175).</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/s41416-020-0846-2</identifier><identifier>PMID: 32350413</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67/1059/99 ; 631/67/1504/1713 ; Adenocarcinoma ; Aged ; Aged, 80 and over ; Albumins - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Carcinoma, Pancreatic Ductal - drug therapy ; Carcinoma, Pancreatic Ductal - mortality ; Clinical trials ; Cytidine deaminase ; Deoxycytidine - administration & dosage ; Deoxycytidine - analogs & derivatives ; Drug Administration Schedule ; Drug Resistance ; Epidemiology ; Female ; Gemcitabine ; Humans ; Male ; Metastases ; Metastasis ; Middle Aged ; Molecular Medicine ; Oncology ; Paclitaxel ; Paclitaxel - administration & dosage ; Pancreas ; Pancreatic cancer ; Pancreatic Neoplasms - drug therapy ; Pancreatic Neoplasms - mortality ; Patients ; Progression-Free Survival ; Quality of life ; Sequential scheduling ; Survival ; Toxicity ; Tumors</subject><ispartof>British journal of cancer, 2020-06, Vol.122 (12), p.1760-1768</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. 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-c470t-13ac3ced72f45ef5aaa7d79cf6e25c753c5186c83a6ec35dd4ecf90c7d621f283</citedby><cites>FETCH-LOGICAL-c470t-13ac3ced72f45ef5aaa7d79cf6e25c753c5186c83a6ec35dd4ecf90c7d621f283</cites><orcidid>0000-0002-1999-0863 ; 0000-0001-9186-1604</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283477/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283477/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32350413$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Corrie, P. G.</creatorcontrib><creatorcontrib>Qian, W.</creatorcontrib><creatorcontrib>Basu, B.</creatorcontrib><creatorcontrib>Valle, J. W.</creatorcontrib><creatorcontrib>Falk, S.</creatorcontrib><creatorcontrib>lwuji, C.</creatorcontrib><creatorcontrib>Wasan, H.</creatorcontrib><creatorcontrib>Palmer, D.</creatorcontrib><creatorcontrib>Scott-Brown, M.</creatorcontrib><creatorcontrib>Wadsley, J.</creatorcontrib><creatorcontrib>Arif, S.</creatorcontrib><creatorcontrib>Bridgewater, J.</creatorcontrib><creatorcontrib>Propper, D.</creatorcontrib><creatorcontrib>Gillmore, R.</creatorcontrib><creatorcontrib>Gopinathan, A.</creatorcontrib><creatorcontrib>Skells, R.</creatorcontrib><creatorcontrib>Bundi, P.</creatorcontrib><creatorcontrib>Brais, R.</creatorcontrib><creatorcontrib>Dalchau, K.</creatorcontrib><creatorcontrib>Bax, L.</creatorcontrib><creatorcontrib>Chhabra, A.</creatorcontrib><creatorcontrib>Machin, A.</creatorcontrib><creatorcontrib>Dayim, A.</creatorcontrib><creatorcontrib>McAdam, K.</creatorcontrib><creatorcontrib>Cummins, S.</creatorcontrib><creatorcontrib>Wall, L.</creatorcontrib><creatorcontrib>Ellis, R.</creatorcontrib><creatorcontrib>Anthoney, A.</creatorcontrib><creatorcontrib>Evans, J.</creatorcontrib><creatorcontrib>Ma, Y. T.</creatorcontrib><creatorcontrib>Isherwood, C.</creatorcontrib><creatorcontrib>Neesse, A.</creatorcontrib><creatorcontrib>Tuveson, D.</creatorcontrib><creatorcontrib>Jodrell, D. I.</creatorcontrib><title>Scheduling nab-paclitaxel combined with gemcitabine as first-line treatment for metastatic pancreatic adenocarcinoma</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Background
Nab-paclitaxel plus gemcitabine (nabP+gemcitabine) offers modest survival gains for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Sequential scheduling of nabP+gemcitabine in a PDAC mouse model improved efficacy; this hypothesis was tested in a clinical trial.
Methods
Patients with previously untreated metastatic PDAC were randomised to receive nabP+gemcitabine administered either concomitantly on the same day, or sequentially, with gemcitabine administered 24 h after nabP. The primary outcome measure was progression-free survival (PFS). Secondary outcome measures were objective response rate (ORR), overall survival (OS), safety, quality of life (QoL) and predictive biomarkers.
Results
In total, 71 patients received sequential (SEQ) and 75 concomitant (CON) treatment. Six-month PFS was 46% with SEQ and 32% with CON scheduling. Median PFS (5.6 versus 4.0 months, hazard ratio [HR] 0.67, 95% confidence interval [95% CI] 0.47–0.95,
p
= 0.022) and ORR (52% versus 31%,
p
= 0.023) favoured the SEQ arm; median OS was 10.2 versus 8.2 months (HR 0.93, 95% CI 0.65–1.33,
p
= 0.70). CTCAE Grade
≥
3 neutropaenia incidence doubled with SEQ therapy but was not detrimental to QoL. Strongly positive tumour epithelial cytidine deaminase (CDA) expression favoured benefit from SEQ therapy (PFS HR 0.31, 95% CI 0.13–0.70).
Conclusions
SEQ delivery of nabP+gemcitabine improved PFS and ORR, with manageable toxicity, but did not significantly improve OS.
Clinical trial registration
ISRCTN71070888; ClinialTrials.gov (NCT03529175).</description><subject>631/67/1059/99</subject><subject>631/67/1504/1713</subject><subject>Adenocarcinoma</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Albumins - administration & dosage</subject><subject>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Carcinoma, Pancreatic Ductal - drug therapy</subject><subject>Carcinoma, Pancreatic Ductal - mortality</subject><subject>Clinical trials</subject><subject>Cytidine deaminase</subject><subject>Deoxycytidine - administration & dosage</subject><subject>Deoxycytidine - analogs & derivatives</subject><subject>Drug Administration Schedule</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Gemcitabine</subject><subject>Humans</subject><subject>Male</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Molecular Medicine</subject><subject>Oncology</subject><subject>Paclitaxel</subject><subject>Paclitaxel - administration & dosage</subject><subject>Pancreas</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - drug therapy</subject><subject>Pancreatic Neoplasms - mortality</subject><subject>Patients</subject><subject>Progression-Free Survival</subject><subject>Quality of life</subject><subject>Sequential scheduling</subject><subject>Survival</subject><subject>Toxicity</subject><subject>Tumors</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1UcuKFDEUDaI47egHuJGA62heVaneCDL4ggEX6jrcvkm6M1QlbZL28fem6HHUhavk3vO4Bw4hTwV_IbiaXlYttBgZl5zxSY9M3iMbMSjJxCTNfbLhnBvGt5JfkEe13vRxyyfzkFwoqQauhdqQ9gkP3p3mmPY0wY4dAefY4IefKeZlF5N39HtsB7r3C3Zg3VCoNMRSG5vXqRUPbfGp0ZALXXyD2qBFpEdIuGL9C86njFAwprzAY_IgwFz9k9v3knx5--bz1Xt2_fHdh6vX1wy14Y0JBajQOyODHnwYAMA4s8UwejmgGRQOYhpxUjB6VINz2mPYcjRulCLISV2SV2ff42m3eIc9Y4HZHktcoPy0GaL9F0nxYPf5mzVdrI3pBs9vDUr-evK12Zt8KqlntlILwSfF9coSZxaWXGvx4e6C4HYtyp6Lsr0ouxZlZdc8-zvaneJ3M50gz4TaobT35c_p_7v-AsGeomQ</recordid><startdate>20200609</startdate><enddate>20200609</enddate><creator>Corrie, P. G.</creator><creator>Qian, W.</creator><creator>Basu, B.</creator><creator>Valle, J. W.</creator><creator>Falk, S.</creator><creator>lwuji, C.</creator><creator>Wasan, H.</creator><creator>Palmer, D.</creator><creator>Scott-Brown, M.</creator><creator>Wadsley, J.</creator><creator>Arif, S.</creator><creator>Bridgewater, J.</creator><creator>Propper, D.</creator><creator>Gillmore, R.</creator><creator>Gopinathan, A.</creator><creator>Skells, R.</creator><creator>Bundi, P.</creator><creator>Brais, R.</creator><creator>Dalchau, K.</creator><creator>Bax, L.</creator><creator>Chhabra, A.</creator><creator>Machin, A.</creator><creator>Dayim, A.</creator><creator>McAdam, K.</creator><creator>Cummins, S.</creator><creator>Wall, L.</creator><creator>Ellis, R.</creator><creator>Anthoney, A.</creator><creator>Evans, J.</creator><creator>Ma, Y. T.</creator><creator>Isherwood, C.</creator><creator>Neesse, A.</creator><creator>Tuveson, D.</creator><creator>Jodrell, D. I.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1999-0863</orcidid><orcidid>https://orcid.org/0000-0001-9186-1604</orcidid></search><sort><creationdate>20200609</creationdate><title>Scheduling nab-paclitaxel combined with gemcitabine as first-line treatment for metastatic pancreatic adenocarcinoma</title><author>Corrie, P. G. ; Qian, W. ; Basu, B. ; Valle, J. W. ; Falk, S. ; lwuji, C. ; Wasan, H. ; Palmer, D. ; Scott-Brown, M. ; Wadsley, J. ; Arif, S. ; Bridgewater, J. ; Propper, D. ; Gillmore, R. ; Gopinathan, A. ; Skells, R. ; Bundi, P. ; Brais, R. ; Dalchau, K. ; Bax, L. ; Chhabra, A. ; Machin, A. ; Dayim, A. ; McAdam, K. ; Cummins, S. ; Wall, L. ; Ellis, R. ; Anthoney, A. ; Evans, J. ; Ma, Y. T. ; Isherwood, C. ; Neesse, A. ; Tuveson, D. ; Jodrell, D. I.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-13ac3ced72f45ef5aaa7d79cf6e25c753c5186c83a6ec35dd4ecf90c7d621f283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>631/67/1059/99</topic><topic>631/67/1504/1713</topic><topic>Adenocarcinoma</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Albumins - administration & dosage</topic><topic>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Carcinoma, Pancreatic Ductal - drug therapy</topic><topic>Carcinoma, Pancreatic Ductal - mortality</topic><topic>Clinical trials</topic><topic>Cytidine deaminase</topic><topic>Deoxycytidine - administration & dosage</topic><topic>Deoxycytidine - analogs & derivatives</topic><topic>Drug Administration Schedule</topic><topic>Drug Resistance</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Gemcitabine</topic><topic>Humans</topic><topic>Male</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Molecular Medicine</topic><topic>Oncology</topic><topic>Paclitaxel</topic><topic>Paclitaxel - administration & dosage</topic><topic>Pancreas</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - drug therapy</topic><topic>Pancreatic Neoplasms - mortality</topic><topic>Patients</topic><topic>Progression-Free Survival</topic><topic>Quality of life</topic><topic>Sequential scheduling</topic><topic>Survival</topic><topic>Toxicity</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Corrie, P. G.</creatorcontrib><creatorcontrib>Qian, W.</creatorcontrib><creatorcontrib>Basu, B.</creatorcontrib><creatorcontrib>Valle, J. W.</creatorcontrib><creatorcontrib>Falk, S.</creatorcontrib><creatorcontrib>lwuji, C.</creatorcontrib><creatorcontrib>Wasan, H.</creatorcontrib><creatorcontrib>Palmer, D.</creatorcontrib><creatorcontrib>Scott-Brown, M.</creatorcontrib><creatorcontrib>Wadsley, J.</creatorcontrib><creatorcontrib>Arif, S.</creatorcontrib><creatorcontrib>Bridgewater, J.</creatorcontrib><creatorcontrib>Propper, D.</creatorcontrib><creatorcontrib>Gillmore, R.</creatorcontrib><creatorcontrib>Gopinathan, A.</creatorcontrib><creatorcontrib>Skells, R.</creatorcontrib><creatorcontrib>Bundi, P.</creatorcontrib><creatorcontrib>Brais, R.</creatorcontrib><creatorcontrib>Dalchau, K.</creatorcontrib><creatorcontrib>Bax, L.</creatorcontrib><creatorcontrib>Chhabra, A.</creatorcontrib><creatorcontrib>Machin, A.</creatorcontrib><creatorcontrib>Dayim, A.</creatorcontrib><creatorcontrib>McAdam, K.</creatorcontrib><creatorcontrib>Cummins, S.</creatorcontrib><creatorcontrib>Wall, L.</creatorcontrib><creatorcontrib>Ellis, R.</creatorcontrib><creatorcontrib>Anthoney, A.</creatorcontrib><creatorcontrib>Evans, J.</creatorcontrib><creatorcontrib>Ma, Y. T.</creatorcontrib><creatorcontrib>Isherwood, C.</creatorcontrib><creatorcontrib>Neesse, A.</creatorcontrib><creatorcontrib>Tuveson, D.</creatorcontrib><creatorcontrib>Jodrell, D. I.</creatorcontrib><collection>Springer Nature OA Free Journals</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 Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Corrie, P. G.</au><au>Qian, W.</au><au>Basu, B.</au><au>Valle, J. W.</au><au>Falk, S.</au><au>lwuji, C.</au><au>Wasan, H.</au><au>Palmer, D.</au><au>Scott-Brown, M.</au><au>Wadsley, J.</au><au>Arif, S.</au><au>Bridgewater, J.</au><au>Propper, D.</au><au>Gillmore, R.</au><au>Gopinathan, A.</au><au>Skells, R.</au><au>Bundi, P.</au><au>Brais, R.</au><au>Dalchau, K.</au><au>Bax, L.</au><au>Chhabra, A.</au><au>Machin, A.</au><au>Dayim, A.</au><au>McAdam, K.</au><au>Cummins, S.</au><au>Wall, L.</au><au>Ellis, R.</au><au>Anthoney, A.</au><au>Evans, J.</au><au>Ma, Y. T.</au><au>Isherwood, C.</au><au>Neesse, A.</au><au>Tuveson, D.</au><au>Jodrell, D. I.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Scheduling nab-paclitaxel combined with gemcitabine as first-line treatment for metastatic pancreatic adenocarcinoma</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2020-06-09</date><risdate>2020</risdate><volume>122</volume><issue>12</issue><spage>1760</spage><epage>1768</epage><pages>1760-1768</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><abstract>Background
Nab-paclitaxel plus gemcitabine (nabP+gemcitabine) offers modest survival gains for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Sequential scheduling of nabP+gemcitabine in a PDAC mouse model improved efficacy; this hypothesis was tested in a clinical trial.
Methods
Patients with previously untreated metastatic PDAC were randomised to receive nabP+gemcitabine administered either concomitantly on the same day, or sequentially, with gemcitabine administered 24 h after nabP. The primary outcome measure was progression-free survival (PFS). Secondary outcome measures were objective response rate (ORR), overall survival (OS), safety, quality of life (QoL) and predictive biomarkers.
Results
In total, 71 patients received sequential (SEQ) and 75 concomitant (CON) treatment. Six-month PFS was 46% with SEQ and 32% with CON scheduling. Median PFS (5.6 versus 4.0 months, hazard ratio [HR] 0.67, 95% confidence interval [95% CI] 0.47–0.95,
p
= 0.022) and ORR (52% versus 31%,
p
= 0.023) favoured the SEQ arm; median OS was 10.2 versus 8.2 months (HR 0.93, 95% CI 0.65–1.33,
p
= 0.70). CTCAE Grade
≥
3 neutropaenia incidence doubled with SEQ therapy but was not detrimental to QoL. Strongly positive tumour epithelial cytidine deaminase (CDA) expression favoured benefit from SEQ therapy (PFS HR 0.31, 95% CI 0.13–0.70).
Conclusions
SEQ delivery of nabP+gemcitabine improved PFS and ORR, with manageable toxicity, but did not significantly improve OS.
Clinical trial registration
ISRCTN71070888; ClinialTrials.gov (NCT03529175).</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32350413</pmid><doi>10.1038/s41416-020-0846-2</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-1999-0863</orcidid><orcidid>https://orcid.org/0000-0001-9186-1604</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0007-0920 |
| ispartof | British journal of cancer, 2020-06, Vol.122 (12), p.1760-1768 |
| issn | 0007-0920 1532-1827 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7283477 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; SpringerLink Journals - AutoHoldings |
| subjects | 631/67/1059/99 631/67/1504/1713 Adenocarcinoma Aged Aged, 80 and over Albumins - administration & dosage Antineoplastic Combined Chemotherapy Protocols - administration & dosage Biomedical and Life Sciences Biomedicine Cancer Research Carcinoma, Pancreatic Ductal - drug therapy Carcinoma, Pancreatic Ductal - mortality Clinical trials Cytidine deaminase Deoxycytidine - administration & dosage Deoxycytidine - analogs & derivatives Drug Administration Schedule Drug Resistance Epidemiology Female Gemcitabine Humans Male Metastases Metastasis Middle Aged Molecular Medicine Oncology Paclitaxel Paclitaxel - administration & dosage Pancreas Pancreatic cancer Pancreatic Neoplasms - drug therapy Pancreatic Neoplasms - mortality Patients Progression-Free Survival Quality of life Sequential scheduling Survival Toxicity Tumors |
| title | Scheduling nab-paclitaxel combined with gemcitabine as first-line treatment for metastatic pancreatic adenocarcinoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T21%3A28%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Scheduling%20nab-paclitaxel%20combined%20with%20gemcitabine%20as%20first-line%20treatment%20for%20metastatic%20pancreatic%20adenocarcinoma&rft.jtitle=British%20journal%20of%20cancer&rft.au=Corrie,%20P.%20G.&rft.date=2020-06-09&rft.volume=122&rft.issue=12&rft.spage=1760&rft.epage=1768&rft.pages=1760-1768&rft.issn=0007-0920&rft.eissn=1532-1827&rft_id=info:doi/10.1038/s41416-020-0846-2&rft_dat=%3Cproquest_pubme%3E2411083047%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2411083047&rft_id=info:pmid/32350413&rfr_iscdi=true |