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dc.contributor.authorSundar, Ren_US
dc.contributor.authorMcVeigh, Ten_US
dc.contributor.authorDolling, Den_US
dc.contributor.authorPetruckevitch, Aen_US
dc.contributor.authorDiamantis, Nen_US
dc.contributor.authorAng, JEen_US
dc.contributor.authorChenard-Poiriér, Men_US
dc.contributor.authorCollins, Den_US
dc.contributor.authorLim, Jen_US
dc.contributor.authorAmeratunga, Men_US
dc.contributor.authorKhan, Ken_US
dc.contributor.authorKaye, SBen_US
dc.contributor.authorBanerji, Uen_US
dc.contributor.authorLopez, Jen_US
dc.contributor.authorGeorge, AJen_US
dc.contributor.authorde Bono, JSen_US
dc.contributor.authorvan der Graaf, WTen_US
dc.date.accessioned2018-09-25T10:30:27Z
dc.date.issued2018-09en_US
dc.identifier.citationEuropean journal of cancer (Oxford, England : 1990), 2018, 101 pp. 55 - 61en_US
dc.identifier.issn0959-8049en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2857
dc.identifier.eissn1879-0852en_US
dc.identifier.doi10.1016/j.ejca.2018.06.003en_US
dc.description.abstract<h4>Background</h4>Adolescent and young adult (AYA) patients with advanced solid tumours are often considered for phase I clinical trials with novel agents. The outcome of AYAs in these trials have not been described before.<h4>Aim</h4>To study the outcome of AYA patients in phase I clinical trials.<h4>Methods</h4>Clinical trial data of AYAs (defined as aged 15-39 years at diagnosis) treated at the Drug Development Unit, Royal Marsden Hospital, between 2002 and 2016, were analysed.<h4>Results</h4>From a prospectively maintained database of 2631 patients treated in phase I trials, 219 AYA patients (8%) were identified. Major tumour types included gynaecological cancer (25%) and sarcoma (18%). Twenty-five (11%) had a known hereditary cancer syndrome (most commonly BRCA). Molecular characterisation of tumours (n = 45) identified mutations most commonly in TP53 (33%), PI3KCA (18%) and KRAS (9%). Therapeutic targets of trials included DNA damage repair (16%), phosphoinositide 3-kinase (PI3K) (16%) and angiogenesis (16%). Grade 3/4 toxicities were experienced in 26% of patients. Of the 214 evaluable patients, objective response rate was 12%, with clinical benefit rate at 6 months of 22%. Median overall survival (OS) was 7.5 months (95% confidence interval: 6.3-9.5), and 2-year OS was 11%. Of patients with responses, 36% were matched to phase I trials based on germline or somatic genetic aberrations.<h4>Conclusion</h4>We describe the outcome of the largest cohort of AYA patients treated in phase I trials. A subgroup of these patients demonstrates benefit, with several durable responses beyond 2 years. A sizeable proportion of AYA patients have cancer syndromes, significant family history or somatic molecular aberrancies which may influence novel therapeutic treatment options.en_US
dc.formatPrint-Electronicen_US
dc.format.extent55 - 61en_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectHumansen_US
dc.subjectNeoplasmsen_US
dc.subjectFatigueen_US
dc.subjectNauseaen_US
dc.subjectVomitingen_US
dc.subjectNuclear Proteinsen_US
dc.subjectTranscription Factorsen_US
dc.subjectAntineoplastic Agentsen_US
dc.subjectCohort Studiesen_US
dc.subjectMutationen_US
dc.subjectAdolescenten_US
dc.subjectAdulten_US
dc.subjectTumor Suppressor Protein p53en_US
dc.subjectProto-Oncogene Proteins p21(ras)en_US
dc.subjectYoung Adulten_US
dc.subjectKaplan-Meier Estimateen_US
dc.subjectOutcome Assessment, Health Careen_US
dc.titleClinical outcomes of adolescents and young adults with advanced solid tumours participating in phase I trials.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-06-12en_US
rioxxterms.versionofrecord10.1016/j.ejca.2018.06.003en_US
rioxxterms.licenseref.startdate2018-09en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfEuropean journal of cancer (Oxford, England : 1990)en_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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicine (de Bono Prostate)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicine Drug Development Unit (de Bono)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical and Translational Sarcoma
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Pharmacology – Adaptive Therapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine Drug Development Unit (de Bono)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Medicine Drug Development Unit (Kaye)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublisheden_US
pubs.volume101en_US
pubs.embargo.termsNot knownen_US
pubs.oa-locationhttps://www.ejcancer.com/article/S0959-8049(18)30895-5/pdfen_US
icr.researchteamMedicine (de Bono Prostate)en_US
icr.researchteamClinical and Translational Sarcomaen_US
icr.researchteamClinical Pharmacology – Adaptive Therapyen_US
icr.researchteamMedicine Drug Development Unit (de Bono)en_US
icr.researchteamProstate Cancer Targeted Therapy Groupen_US
icr.researchteamMedicine Drug Development Unit (Kaye)en_US
dc.contributor.icrauthorBanerji, Udaien_US
dc.contributor.icrauthorKaye, Stanley Bernarden_US
dc.contributor.icrauthorLopez, Juanitaen_US
dc.contributor.icrauthorDe Bono, Johannen_US
dc.contributor.icrauthorvan der Graaf, Wilhelminaen_US
dc.contributor.icrauthorTurner, Lydiaen_US
dc.contributor.icrauthorMcVeigh, Terrien_US


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