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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.abstract<h4>Background</h4>A 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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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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