Phase III study of pemetrexed plus carboplatin compared with etoposide plus carboplatin in chemotherapy-naive patients with extensive-stage small-cell lung cancer.

2.50
Hdl Handle:
http://hdl.handle.net/10541/87687
Title:
Phase III study of pemetrexed plus carboplatin compared with etoposide plus carboplatin in chemotherapy-naive patients with extensive-stage small-cell lung cancer.
Authors:
Socinski, Mark A; Smit, Egbert; Lorigan, Paul C ( 0000-0002-8875-2164 ) ; Konduri, Kartik; Reck, Martin; Szczesna, Aleksandra; Blakely, Johnetta; Serwatowski, Piotr; Karaseva, Nina A; Ciuleanu, Tudor; Jassem, Jacek; Dediu, Mircea; Hong, Shengyan; Visseren-Grul, Carla; Hanauske, Axel-Rainer; Obasaju, Coleman K; Guba, Susan C; Thatcher, Nick
Abstract:
PURPOSE: Following a phase II trial in which pemetrexed-platinum demonstrated similar activity to that of historical etoposide-platinum controls, a phase III study was conducted to compare pemetrexed-carboplatin with etoposide-carboplatin for the treatment of extensive-stage small-cell lung cancer (ES-SCLC). PATIENTS AND METHODS: Chemotherapy-naive patients with ES-SCLC and an Eastern Cooperative Oncology Group performance status of zero to 2 were randomly assigned to receive pemetrexed-carboplatin (pemetrexed 500 mg/m(2) on day 1; carboplatin at area under the serum concentration-time curve [AUC] 5 on day 1) or etoposide-carboplatin (etoposide 100 mg/m(2) on days 1 through 3; carboplatin AUC 5 on day 1) every 3 weeks for up to six cycles. The primary objective of the study was noninferiority of pemetrexed-carboplatin overall survival with a 15% margin. RESULTS: Accrual was terminated with 908 of 1,820 patients enrolled after results of a planned interim analysis. In the final analysis, pemetrexed-carboplatin was inferior to etoposide-carboplatin for overall survival (median, 8.1 v 10.6 months; hazard ratio [HR],1.56; 95% CI, 1.27 to 1.92; log-rank P < .01) and progression-free survival (median, 3.8 v 5.4 months; HR, 1.85; 95% CI, 1.58 to 2.17; log-rank P < .01). Objective response rates were also significantly lower for pemetrexed-carboplatin (31% v 52%; P < .001). Pemetrexed-carboplatin had lower grade 3 to 4 neutropenia, febrile neutropenia, and leukopenia than etoposide-carboplatin; grade 3 to 4 thrombocytopenia was comparable between arms and anemia was higher in the pemetrexed-carboplatin arm. CONCLUSION: Pemetrexed-carboplatin is inferior for the treatment of ES-SCLC. Planned translational research and pharmacogenomic analyses of tumor and blood samples may help explain the study results and provide insight into new treatment strategies.
Affiliation:
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA. socinski@med.unc.edu
Citation:
Phase III study of pemetrexed plus carboplatin compared with etoposide plus carboplatin in chemotherapy-naive patients with extensive-stage small-cell lung cancer. 2009, 27 (28):4787-92 J. Clin. Oncol.
Journal:
Journal of Clinical Oncology
Issue Date:
1-Oct-2009
URI:
http://hdl.handle.net/10541/87687
DOI:
10.1200/JCO.2009.23.1548
PubMed ID:
19720897
Type:
Article
Language:
en
ISSN:
1527-7755
Appears in Collections:
All Christie Publications ; Medical Oncology

Full metadata record

DC FieldValue Language
dc.contributor.authorSocinski, Mark Aen
dc.contributor.authorSmit, Egberten
dc.contributor.authorLorigan, Paul Cen
dc.contributor.authorKonduri, Kartiken
dc.contributor.authorReck, Martinen
dc.contributor.authorSzczesna, Aleksandraen
dc.contributor.authorBlakely, Johnettaen
dc.contributor.authorSerwatowski, Piotren
dc.contributor.authorKaraseva, Nina Aen
dc.contributor.authorCiuleanu, Tudoren
dc.contributor.authorJassem, Jaceken
dc.contributor.authorDediu, Mirceaen
dc.contributor.authorHong, Shengyanen
dc.contributor.authorVisseren-Grul, Carlaen
dc.contributor.authorHanauske, Axel-Raineren
dc.contributor.authorObasaju, Coleman Ken
dc.contributor.authorGuba, Susan Cen
dc.contributor.authorThatcher, Nicken
dc.date.accessioned2009-12-09T14:46:26Z-
dc.date.available2009-12-09T14:46:26Z-
dc.date.issued2009-10-01-
dc.identifier.citationPhase III study of pemetrexed plus carboplatin compared with etoposide plus carboplatin in chemotherapy-naive patients with extensive-stage small-cell lung cancer. 2009, 27 (28):4787-92 J. Clin. Oncol.en
dc.identifier.issn1527-7755-
dc.identifier.pmid19720897-
dc.identifier.doi10.1200/JCO.2009.23.1548-
dc.identifier.urihttp://hdl.handle.net/10541/87687-
dc.description.abstractPURPOSE: Following a phase II trial in which pemetrexed-platinum demonstrated similar activity to that of historical etoposide-platinum controls, a phase III study was conducted to compare pemetrexed-carboplatin with etoposide-carboplatin for the treatment of extensive-stage small-cell lung cancer (ES-SCLC). PATIENTS AND METHODS: Chemotherapy-naive patients with ES-SCLC and an Eastern Cooperative Oncology Group performance status of zero to 2 were randomly assigned to receive pemetrexed-carboplatin (pemetrexed 500 mg/m(2) on day 1; carboplatin at area under the serum concentration-time curve [AUC] 5 on day 1) or etoposide-carboplatin (etoposide 100 mg/m(2) on days 1 through 3; carboplatin AUC 5 on day 1) every 3 weeks for up to six cycles. The primary objective of the study was noninferiority of pemetrexed-carboplatin overall survival with a 15% margin. RESULTS: Accrual was terminated with 908 of 1,820 patients enrolled after results of a planned interim analysis. In the final analysis, pemetrexed-carboplatin was inferior to etoposide-carboplatin for overall survival (median, 8.1 v 10.6 months; hazard ratio [HR],1.56; 95% CI, 1.27 to 1.92; log-rank P < .01) and progression-free survival (median, 3.8 v 5.4 months; HR, 1.85; 95% CI, 1.58 to 2.17; log-rank P < .01). Objective response rates were also significantly lower for pemetrexed-carboplatin (31% v 52%; P < .001). Pemetrexed-carboplatin had lower grade 3 to 4 neutropenia, febrile neutropenia, and leukopenia than etoposide-carboplatin; grade 3 to 4 thrombocytopenia was comparable between arms and anemia was higher in the pemetrexed-carboplatin arm. CONCLUSION: Pemetrexed-carboplatin is inferior for the treatment of ES-SCLC. Planned translational research and pharmacogenomic analyses of tumor and blood samples may help explain the study results and provide insight into new treatment strategies.en
dc.language.isoenen
dc.subjectAnaemiaen
dc.subjectLung Canceren
dc.subject.meshAged-
dc.subject.meshAnemia-
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols-
dc.subject.meshCarboplatin-
dc.subject.meshEtoposide-
dc.subject.meshFatigue-
dc.subject.meshFemale-
dc.subject.meshGlutamates-
dc.subject.meshGuanine-
dc.subject.meshHumans-
dc.subject.meshKaplan-Meiers Estimate-
dc.subject.meshLung Neoplasms-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshNausea-
dc.subject.meshNeutropenia-
dc.subject.meshSmall Cell Lung Carcinoma-
dc.subject.meshTreatment Outcome-
dc.titlePhase III study of pemetrexed plus carboplatin compared with etoposide plus carboplatin in chemotherapy-naive patients with extensive-stage small-cell lung cancer.en
dc.typeArticleen
dc.contributor.departmentLineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA. socinski@med.unc.eduen
dc.identifier.journalJournal of Clinical Oncologyen

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