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dc.contributor.authorEarly Breast Cancer Trialists' Collaborative Group (EBCTCG)en_US
dc.date.accessioned2019-05-22T08:13:28Z
dc.date.issued2019-04
dc.identifier.citationLancet (London, England), 2019, 393 (10179), pp. 1440 - 1452
dc.identifier.issn0140-6736
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3231
dc.identifier.eissn1474-547X
dc.identifier.doi10.1016/s0140-6736(18)33137-4
dc.description.abstractBackground Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy. Methods To clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs). Findings Individual patient data were provided for 26 of 33 relevant trials identified, comprising 37 298 (93%) of 40 070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28·0% vs 31·4%; RR 0·86, 95% CI 0·82-0·89; p<0·0001). 10-year breast cancer mortality was similarly reduced (18·9% vs 21·3%; RR 0·87, 95% CI 0·83-0·92; p<0·0001), as was all-cause mortality (22·1% vs 24·8%; RR 0·87, 95% CI 0·83-0·91; p<0·0001). Death without recurrence was, if anything, lower with dose-intense than with standard-schedule chemotherapy (10-year risk 4·1% vs 4·6%; RR 0·88, 95% CI 0·78-0·99; p=0·034). Recurrence reductions were similar in the seven trials (n=10 004) that compared 2-weekly chemotherapy with the same chemotherapy given 3-weekly (10-year risk 24·0% vs 28·3%; RR 0·83, 95% CI 0·76-0·91; p<0·0001), in the six trials (n=11 028) of sequential versus concurrent anthracycline plus taxane chemotherapy (28·1% vs 31·3%; RR 0·87, 95% CI 0·80-0·94; p=0·0006), and in the six trials (n=6532) testing both shorter intervals and sequential administration (30·4% vs 35·0%; RR 0·82, 95% CI 0·74-0·90; p<0·0001). The proportional reductions in recurrence with dose-intense chemotherapy were similar and highly significant (p<0·0001) in oestrogen receptor (ER)-positive and ER-negative disease and did not differ significantly by other patient or tumour characteristics. Interpretation Increasing the dose intensity of adjuvant chemotherapy by shortening the interval between treatment cycles, or by giving individual drugs sequentially rather than giving the same drugs concurrently, moderately reduces the 10-year risk of recurrence and death from breast cancer without increasing mortality from other causes. Funding Cancer Research UK, Medical Research Council.
dc.formatPrint-Electronic
dc.format.extent1440 - 1452
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectEarly Breast Cancer Trialists' Collaborative Group (EBCTCG)
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectAntineoplastic Agents
dc.subjectDrug Administration Schedule
dc.subjectFemale
dc.titleIncreasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials.
dc.typeJournal Article
dcterms.dateAccepted2018-11-29
rioxxterms.versionofrecord10.1016/s0140-6736(18)33137-4
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-04
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfLancet (London, England)
pubs.issue10179
pubs.notesNo embargo
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/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrinology
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/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology/Endocrinology (hon.)
pubs.publication-statusPublished
pubs.volume393
pubs.embargo.termsNo embargo
icr.researchteamClinical Trials & Statistics Uniten_US
icr.researchteamEndocrinologyen_US
dc.contributor.icrauthorBliss, Judithen
dc.contributor.icrauthorYarnold, Johnen
dc.contributor.icrauthorDowsett, Mitchen
dc.contributor.icrauthorKilburn, Lucyen


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