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dc.contributor.authorEarl, Helena M
dc.contributor.authorHiller, Louise
dc.contributor.authorHoward, Helen C
dc.contributor.authorDunn, Janet A
dc.contributor.authorYoung, Jennie
dc.contributor.authorBowden, Sarah J
dc.contributor.authorMcDermaid, Michelle
dc.contributor.authorWaterhouse, Anna K
dc.contributor.authorWilson, Gregory
dc.contributor.authorAgrawal, Rajiv
dc.contributor.authorO'Reilly, Susan
dc.contributor.authorBowman, Angela
dc.contributor.authorRitchie, Diana M
dc.contributor.authorGoodman, Andrew
dc.contributor.authorHickish, Tamas
dc.contributor.authorMcAdam, Karen
dc.contributor.authorCameron, David
dc.contributor.authorDodwell, David
dc.contributor.authorRea, Daniel W
dc.contributor.authorCaldas, Carlos
dc.contributor.authorProvenzano, Elena
dc.contributor.authorAbraham, Jean E
dc.contributor.authorCanney, Peter
dc.contributor.authorCrown, John P
dc.contributor.authorKennedy, M John
dc.contributor.authorColeman, Robert
dc.contributor.authorLeonard, Robert C
dc.contributor.authorCarmichael, James A
dc.contributor.authorWardley, Andrew M
dc.contributor.authorPoole, Christopher J
dc.contributor.authortAnGo trial collaborators
dc.date.accessioned2017-05-22T10:50:36Z
dc.date.available2017-05-22T10:50:36Z
dc.date.issued2017-06
dc.identifier.issn1470-2045
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/264339
dc.description.abstractBACKGROUND: The tAnGo trial was designed to investigate the potential role of gemcitabine when added to anthracycline and taxane-containing adjuvant chemotherapy for early breast cancer. When this study was developed, gemcitabine had shown significant activity in metastatic breast cancer, and there was evidence of a favourable interaction with paclitaxel. METHODS: tAnGo was an international, open-label, randomised, phase 3 superiority trial that enrolled women aged 18 years or older with newly diagnosed, early-stage breast cancer who had a definite indication for chemotherapy, any nodal status, any hormone receptor status, Eastern Cooperative Oncology Group performance status of 0-1, and adequate bone marrow, hepatic, and renal function. Women were recruited from 127 clinical centres and hospitals in the UK and Ireland, and randomly assigned (1:1) to one of two treatment regimens: epirubicin, cyclophosphamide, and paclitaxel (four cycles of 90 mg/m2 intravenously administered epirubicin and 600 mg/m2 intravenously administered cyclophosphamide on day 1 every 3 weeks, followed by four cycles of 175 mg/m2 paclitaxel as a 3 h infusion on day 1 every 3 weeks) or epirubicin, cyclophosphamide, and paclitaxel plus gemcitabine (the same chemotherapy regimen as the other group, with the addition of 1250 mg/m2 gemcitabine to the paclitaxel cycles, administered intravenously as a 0·5 h infusion on days 1 and 8 every 3 weeks). Patients were randomly assigned by a central computerised deterministic minimisation procedure, with stratification by country, age, radiotherapy intent, nodal status, and oestrogen receptor and HER-2 status. The primary endpoint was disease-free survival and the trial aimed to detect 5% differences in 5-year disease-free survival between the treatment groups. Recruitment completed in 2004 and this is the final, intention-to-treat analysis. This trial is registered with EudraCT (2004-002927-41), ISRCTN (51146252), and ClinicalTrials.gov (NCT00039546). FINDINGS: Between Aug 22, 2001, and Nov 26, 2004, 3152 patients were enrolled and randomly assigned to epirubicin, cyclophosphamide, paclitaxel, and gemcitabine (gemcitabine group; n=1576) or to epirubicin, cyclophosphamide, and paclitaxel (control group; n=1576). 11 patients (six in the gemcitabine group and five in the control group) were ineligible because of pre-existing metastases and were therefore excluded from the analysis. At this protocol-specified final analysis (median follow-up 10 years [IQR 10-10]), 1087 disease-free survival events and 914 deaths had occurred. Disease-free survival did not differ significantly between the treatment groups at 10 years (65% [63-68] in the gemcitabine group vs 65% [62-67] in the control group), and median disease-free survival was not reached (adjusted hazard ratio 0·97 [95% CI 0·86-1·10], p=0·64). Toxicity, dose intensity, and a detailed safety substudy showed both regimens to be safe, deliverable, and tolerable. Grade 3 and 4 toxicities were reported at expected levels in both groups. The most common were neutropenia (527 [34%] of 1565 patients in the gemcitabine group vs 412 [26%] of 1567 in the control group), myalgia and arthralgia (207 [13%] vs 186 [12%]), fatigue (207 [13%] vs 152 [10%]), infection (202 [13%] vs 141 [9%]), vomiting (143 [9%] vs 108 [7%]), and nausea (132 [8%] vs 102 [7%]). INTERPRETATION: The addition of gemcitabine to anthracycline and taxane-based adjuvant chemotherapy at this dose and schedule confers no therapeutic advantage in terms of disease-free survival in early breast cancer, although it can cause increased toxicity. Therefore, gemcitabine has not been added to standard adjuvant chemotherapy in breast cancer for any subgroup. FUNDING: Cancer Research UK core funding for Clinical Trials Unit at the University of Birmingham, Eli Lilly, Bristol-Myers Squibb, and Pfizer.
dc.description.sponsorshipCancer Research UK core funding for Clinical Trials Unit at the University of Birmingham, Eli Lilly, Bristol-Myers Squibb, and Pfizer
dc.format.mediumPrint-Electronic
dc.languageeng
dc.language.isoen
dc.publisherElsevier BV
dc.subjecttAnGo trial collaborators
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectLymphatic Metastasis
dc.subjectPaclitaxel
dc.subjectCyclophosphamide
dc.subjectEpirubicin
dc.subjectReceptor, erbB-2
dc.subjectReceptors, Estrogen
dc.subjectReceptors, Progesterone
dc.subjectDeoxycytidine
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectDisease-Free Survival
dc.subjectChemotherapy, Adjuvant
dc.subjectRadiotherapy
dc.subjectMastectomy, Segmental
dc.subjectSurvival Rate
dc.subjectFollow-Up Studies
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectIntention to Treat Analysis
dc.titleAddition of gemcitabine to paclitaxel, epirubicin, and cyclophosphamide adjuvant chemotherapy for women with early-stage breast cancer (tAnGo): final 10-year follow-up of an open-label, randomised, phase 3 trial.
dc.typeArticle
prism.endingPage769
prism.publicationDate2017
prism.publicationNameLancet Oncol
prism.startingPage755
prism.volume18
dc.identifier.doi10.17863/CAM.9805
dcterms.dateAccepted2017-03-01
rioxxterms.versionofrecord10.1016/S1470-2045(17)30319-4
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2017-06
dc.contributor.orcidEarl, Helena [0000-0003-1549-8094]
dc.contributor.orcidCaldas, Carlos [0000-0003-3547-1489]
dc.contributor.orcidAbraham, Jean [0000-0003-0688-4807]
dc.identifier.eissn1474-5488
rioxxterms.typeJournal Article/Review
pubs.funder-project-idCancer Research Uk (None)
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (NF-SI-0515-10090)
pubs.funder-project-idCancer Research UK (CB4140)
pubs.funder-project-idCancer Research UK (unknown)
pubs.funder-project-idCancer Research UK (60098573)
pubs.funder-project-idCancer Research UK (unknown)
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (unknown)
pubs.funder-project-idEuropean Commission (260791)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (RG51913)
pubs.funder-project-idCancer Research Uk (None)
pubs.funder-project-idEuropean Commission FP7 Network of Excellence (NoE) (260791)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
pubs.funder-project-idCancer Research Uk (None)
pubs.funder-project-idAcademy of Medical Sciences (unknown)
pubs.funder-project-idMedical Research Council (MR/M008975/1)
pubs.funder-project-idAcademy of Medical Sciences (ALI 01/08/14)
pubs.funder-project-idPathological Society of Great Britain & Ireland (CDF 2012/01)
pubs.funder-project-idEuropean Commission FP7 Collaborative projects (CP) (258967)
pubs.funder-project-idCancer Research UK (C507/A16278)
pubs.funder-project-idEuropean Commission (258967)
pubs.funder-project-idCancer Research UK (20544)
pubs.funder-project-idMedical Research Council (MR/P012442/1)
pubs.funder-project-idEuropean Commission and European Federation of Pharmaceutical Industries and Associations (EFPIA) FP7 Innovative Medicines Initiative (IMI) (115749)
pubs.funder-project-idEuropean Commission (242006)
pubs.funder-project-idEuropean Research Council (694620)
pubs.funder-project-idCancer Research UK (A24622)
cam.issuedOnline2017-05-04
rioxxterms.freetoread.startdate2017-11-04


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