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dc.contributor.authorFresneau, Ben_US
dc.contributor.authorHackshaw, Aen_US
dc.contributor.authorHawkins, DSen_US
dc.contributor.authorPaulussen, Men_US
dc.contributor.authorAnderson, JRen_US
dc.contributor.authorJudson, Ien_US
dc.contributor.authorLitière, Sen_US
dc.contributor.authorDirksen, Uen_US
dc.contributor.authorLewis, Ien_US
dc.contributor.authorvan den Berg, Hen_US
dc.contributor.authorGaspar, Nen_US
dc.contributor.authorGelderblom, Hen_US
dc.contributor.authorWhelan, Jen_US
dc.contributor.authorBoddy, AVen_US
dc.contributor.authorWheatley, Ken_US
dc.contributor.authorPignon, JPen_US
dc.contributor.authorDe Vathaire, Fen_US
dc.contributor.authorLe Deley, MCen_US
dc.contributor.authorLe Teuff, Gen_US
dc.date.accessioned2018-02-20T10:52:07Z
dc.date.issued2017-08en_US
dc.identifier.citationPediatric blood & cancer, 2017, 64 (8)en_US
dc.identifier.issn1545-5009en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1358
dc.identifier.eissn1545-5017en_US
dc.identifier.doi10.1002/pbc.26457en_US
dc.description.abstractA marginal interaction between sex and the type of alkylating agent was observed for event-free survival in the Euro-EWING99-R1 randomized controlled trial (RCT) comparing cyclophosphamide and ifosfamide in Ewing sarcoma. To further evaluate this interaction, we performed an individual patient data meta-analysis of RCTs assessing cyclophosphamide versus ifosfamide in any type of cancer.A literature search produced two more eligible RCTs (EICESS92 and IRS-IV). The endpoints were progression-free survival (PFS, main endpoint) and overall survival (OS). The hazard ratios (HRs) of the treatment-by-sex interaction and their 95% confidence interval (95% CI) were assessed using stratified multivariable Cox models. Heterogeneity of the interaction across age categories and trials was explored. We also assessed this interaction for severe acute toxicity using logistic models.The meta-analysis comprised 1,528 pediatric and young adult sarcoma patients from three RCTs: Euro-EWING99-R1 (n = 856), EICESS92 (n = 155), and IRS-IV (n = 517). There were 224 PFS events in Euro-EWING99-R1 and 200 in the validation set (EICESS92 + IRS-IV), and 171 and 154 deaths in each dataset, respectively. The estimated treatment-by-sex interaction for PFS in Euro-EWING99-R1 (HR = 1.73, 95% CI = 1.00-3.00) was not replicated in the validation set (HR = 0.97, 95% CI = 0.55-1.72), without heterogeneity across trials (P = 0.62). In the pooled analysis, the treatment-by-sex interaction was not significant (HR = 1.31, 95% CI = 0.89-1.95, P = 0.17), without heterogeneity across age categories (P = 0.88) and trials (P = 0.36). Similar results were observed for OS. No significant treatment-by-sex interaction was observed for leucopenia/neutropenia (P = 0.45), infection (P = 0.64), or renal toxicity (P = 0.20).Our meta-analysis did not confirm the hypothesis of a treatment-by-sex interaction on efficacy or toxicity outcomes.en_US
dc.formatPrint-Electronicen_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectHumansen_US
dc.subjectSarcomaen_US
dc.subjectCyclophosphamideen_US
dc.subjectIfosfamideen_US
dc.subjectAntineoplastic Agentsen_US
dc.subjectAlkylating Agentsen_US
dc.subjectSex Characteristicsen_US
dc.subjectFemaleen_US
dc.subjectMaleen_US
dc.subjectRandomized Controlled Trials as Topicen_US
dc.titleInvestigating the heterogeneity of alkylating agents' efficacy and toxicity between sexes: A systematic review and meta-analysis of randomized trials comparing cyclophosphamide and ifosfamide (MAIAGE study).en_US
dc.typeJournal Article
dcterms.dateAccepted2016-12-22en_US
rioxxterms.versionofrecord10.1002/pbc.26457en_US
rioxxterms.licenseref.startdate2017-08en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfPediatric blood & canceren_US
pubs.issue8en_US
pubs.notesNot knownen_US
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/Sarcoma Clinical Trials
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublisheden_US
pubs.volume64en_US
pubs.embargo.termsNot knownen_US
icr.researchteamSarcoma Clinical Trialsen_US
dc.contributor.icrauthorJudson, Ianen_US
dc.contributor.icrauthorMarsden,en_US


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