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dc.contributor.authorCoombes, RC
dc.contributor.authorKilburn, LS
dc.contributor.authorTubiana-Mathieu, N
dc.contributor.authorOlmos, T
dc.contributor.authorVan Bochove, A
dc.contributor.authorPerez-Lopez, FR
dc.contributor.authorPalmieri, C
dc.contributor.authorStebbing, J
dc.contributor.authorBliss, JM
dc.date.accessioned2019-12-16T14:23:31Z
dc.date.issued2016-06
dc.identifier.citationEuropean journal of cancer (Oxford, England : 1990), 2016, 60 pp. 146 - 153
dc.identifier.issn0959-8049
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3475
dc.identifier.eissn1879-0852
dc.identifier.doi10.1016/j.ejca.2016.03.001
dc.description.abstractBackground The hormonal manipulation 5-Fluoro-uracil Epirubicin Cyclophosphamide (HMFEC) trial was developed at a time of uncertainty around the dose intensity of chemotherapy given to premenopausal patients with node positive breast cancer and to the benefits of tailored endocrine therapy in such patients.Patients and methods HMFEC was a multi-centre, phase III, open label, randomised controlled trial with a 2 × 2 factorial design. Eligible patients were premenopausal with node positive early breast cancer; significant cardiac disease or uncontrolled hypertension was exclusion criterion. Patients were allocated to receive either eight cycles of FE50C or FE75C (given 3 weekly) with or without hormone manipulation (HM; tamoxifen or luteinising hormone releasing hormone (LHRH) agonists according to residual hormone levels at the end of chemotherapy) irrespective of ER status. The primary end-point was disease free survival (DFS). Principal analyses were by intention to treat (ITT); however, to reflect contemporary practice, subgroup analyses according to ER status were also conducted. The mature follow-up now available from this modest sized trial enables presentation of definitive results.Results Between 1992 and 2000 a total of 785 patients were randomised into the HMFEC trial (203 FE50C-HM, 191 FE50C+HM, 198 FE75C-HM, 193 FE75C+HM). At a median follow-up of 7.4 years, 245 DFS events have been reported (92 ER-, 153 ER+/unknown). The effects on DFS were not statistically significantly different according to epirubicin dose (hazard ratio [HR] = 0.82, 95% confidence interval [CI] 0.63-1.06; p = 0.13 FE75C versus FE50C); however, FE75C appeared to induce more alopecia and neutropenia. No statistically significant evidence was observed to support an improvement in DFS in patients allocated HM either overall (HR = 0.88, 95% CI 0.68-1.13; p = 0.32) or in patients with ER+/unknown disease (HR = 0.85, 95% CI 0.62-1.17; p = 0.32) although effect sizes are consistent with worthwhile clinical effects. Overall, there was no evidence of a difference in survival between any of the four treatment groups of the trial.Conclusion Higher doses of epirubicin cause more adverse events in the absence of clear improvement in overall survival. Endocrine therapy with either tamoxifen or goserelin provided no significant added benefit to cytotoxic chemotherapy in this group of patients.Trial registration number ISRCTN98335268.
dc.formatPrint-Electronic
dc.format.extent146 - 153
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectCyclophosphamide
dc.subjectFluorouracil
dc.subjectEpirubicin
dc.subjectAntineoplastic Agents, Hormonal
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectTreatment Outcome
dc.subjectPremenopause
dc.subjectDose-Response Relationship, Drug
dc.subjectAdult
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectKaplan-Meier Estimate
dc.titleEpirubicin dose and sequential hormonal therapy-Mature results of the HMFEC randomised phase III trial in premenopausal patients with node positive early breast cancer.
dc.typeJournal Article
dcterms.dateAccepted2016-03-01
rioxxterms.versionofrecord10.1016/j.ejca.2016.03.001
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2016-06
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfEuropean journal of cancer (Oxford, England : 1990)
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit
pubs.publication-statusPublished
pubs.volume60
pubs.embargo.termsNot known
icr.researchteamClinical Trials & Statistics Uniten_US
dc.contributor.icrauthorBliss, Judithen
dc.contributor.icrauthorKilburn, Lucyen


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