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dc.contributor.authorFresneau, B
dc.contributor.authorHackshaw, A
dc.contributor.authorHawkins, DS
dc.contributor.authorPaulussen, M
dc.contributor.authorAnderson, JR
dc.contributor.authorJudson, I
dc.contributor.authorLitière, S
dc.contributor.authorDirksen, U
dc.contributor.authorLewis, I
dc.contributor.authorvan den Berg, H
dc.contributor.authorGaspar, N
dc.contributor.authorGelderblom, H
dc.contributor.authorWhelan, J
dc.contributor.authorBoddy, AV
dc.contributor.authorWheatley, K
dc.contributor.authorPignon, JP
dc.contributor.authorDe Vathaire, F
dc.contributor.authorLe Deley, MC
dc.contributor.authorLe Teuff, G
dc.date.accessioned2018-02-20T10:52:07Z
dc.date.issued2017-08
dc.identifier.citationPediatric blood & cancer, 2017, 64 (8)
dc.identifier.issn1545-5009
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1358
dc.identifier.eissn1545-5017
dc.identifier.doi10.1002/pbc.26457
dc.description.abstractBackground 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.Methods 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.Results 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).Conclusion Our meta-analysis did not confirm the hypothesis of a treatment-by-sex interaction on efficacy or toxicity outcomes.
dc.formatPrint-Electronic
dc.languageeng
dc.language.isoeng
dc.subjectHumans
dc.subjectSarcoma
dc.subjectCyclophosphamide
dc.subjectIfosfamide
dc.subjectAntineoplastic Agents
dc.subjectAlkylating Agents
dc.subjectSex Characteristics
dc.subjectFemale
dc.subjectMale
dc.subjectRandomized Controlled Trials as Topic
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).
dc.typeJournal Article
dcterms.dateAccepted2016-12-22
rioxxterms.versionofrecord10.1002/pbc.26457
rioxxterms.licenseref.startdate2017-08
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfPediatric blood & cancer
pubs.issue8
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/Sarcoma Clinical Trials
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
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-statusPublished
pubs.volume64
pubs.embargo.termsNot known
icr.researchteamSarcoma Clinical Trialsen_US
dc.contributor.icrauthorJudson, Ianen
dc.contributor.icrauthorMarsden,en


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