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dc.contributor.authorBisogno, G
dc.contributor.authorDe Salvo, GL
dc.contributor.authorBergeron, C
dc.contributor.authorGallego Melcón, S
dc.contributor.authorMerks, JH
dc.contributor.authorKelsey, A
dc.contributor.authorMartelli, H
dc.contributor.authorMinard-Colin, V
dc.contributor.authorOrbach, D
dc.contributor.authorGlosli, H
dc.contributor.authorChisholm, J
dc.contributor.authorCasanova, M
dc.contributor.authorZanetti, I
dc.contributor.authorDevalck, C
dc.contributor.authorBen-Arush, M
dc.contributor.authorMudry, P
dc.contributor.authorFerman, S
dc.contributor.authorJenney, M
dc.contributor.authorFerrari, A
dc.contributor.authorEuropean paediatric Soft tissue sarcoma Study Group
dc.date.accessioned2019-12-06T15:43:26Z
dc.date.issued2019-11
dc.identifier.citationThe Lancet. Oncology, 2019, 20 (11), pp. 1566 - 1575
dc.identifier.issn1470-2045
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3449
dc.identifier.eissn1474-5488
dc.identifier.doi10.1016/s1470-2045(19)30617-5
dc.description.abstractBackground For more than three decades, standard treatment for rhabdomyosarcoma in Europe has included 6 months of chemotherapy. The European paediatric Soft tissue sarcoma Study Group (EpSSG) aimed to investigate whether prolonging treatment with maintenance chemotherapy would improve survival in patients with high-risk rhabdomyosarcoma.Methods RMS 2005 was a multicentre, open-label, randomised, controlled, phase 3 trial done at 102 hospitals in 14 countries. We included patients aged 6 months to 21 years with rhabdomyosarcoma who were considered to be at high risk of relapse: those with non-metastatic incompletely resected embryonal rhabdomyosarcoma occurring at unfavourable sites with unfavourable age (≥10 years) or tumour size (>5 cm), or both; those with any non-metastatic rhabdomyosarcoma with nodal involvement; and those with non-metastatic alveolar rhabdomyosarcoma but without nodal involvement. Patients in remission after standard treatment (nine cycles of ifosfamide, vincristine, dactinomycin with or without doxorubicin, and surgery or radiotherapy, or both) were randomly assigned (1:1) to stop treatment or continue maintenance chemotherapy (six cycles of intravenous vinorelbine 25 mg/m 2 on days 1, 8, and 15, and daily oral cyclophosphamide 25 mg/m 2 , on days 1-28). Randomisation was done by use of a web-based system and was stratified (block size of four) by enrolling country and risk subgroup. Neither investigators nor patients were masked to treatment allocation. The primary outcome was disease-free survival in the intention-to-treat population. Secondary outcomes were overall survival and toxicity. This trial is registered with EudraCT, number 2005-000217-35, and ClinicalTrials.gov, number NCT00339118, and follow-up is ongoing.Findings Between April 20, 2006, and Dec 21, 2016, 371 patients were enrolled and randomly assigned to the two groups: 186 to stop treatment and 185 to receive maintenance chemotherapy. Median follow-up was 60·3 months (IQR 32·4-89·4). In the intention-to-treat population, 5-year disease-free survival was 77·6% (95% CI 70·6-83·2) with maintenance chemotherapy versus 69·8% (62·2-76·2) without maintenance chemotherapy (hazard ratio [HR] 0·68 [95% CI 0·45-1·02]; p=0·061), and 5-year overall survival was 86·5% (95% CI 80·2-90·9) with maintenance chemotherapy versus 73·7% (65·8-80·1) without (HR 0·52 [95% CI 0·32-0·86]; p=0·0097). Toxicity was manageable in patients who received maintenance chemotherapy: 136 (75%) of 181 patients had grade 3-4 leucopenia, 148 (82%) had grade 3-4 neutropenia, 19 (10%) had anaemia, two (1%) had thrombocytopenia, and 56 (31%) had an infection. One (1%) patient had a grade 4 non-haematological toxicity (neurotoxicity). Two treatment-related serious adverse events occurred: one case of inappropriate antidiuretic hormone secretion and one of a severe steppage gait with limb pain, both of which resolved.Interpretation Adding maintenance chemotherapy seems to improve survival for patients with high-risk rhabdomyosarcoma. This approach will be the new standard of care for patients with high-risk rhabdomyosarcoma in future EpSSG trials.Funding Fondazione Città della Speranza, Association Léon Berard Enfant Cancéreux, Clinical Research Hospital Program (French Ministry of Health), and Cancer Research UK.
dc.formatPrint-Electronic
dc.format.extent1566 - 1575
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.subjectEuropean paediatric Soft tissue sarcoma Study Group
dc.subjectHumans
dc.subjectRhabdomyosarcoma, Alveolar
dc.subjectRhabdomyosarcoma, Embryonal
dc.subjectDisease Progression
dc.subjectCyclophosphamide
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectDisease-Free Survival
dc.subjectRemission Induction
dc.subjectRisk Assessment
dc.subjectRisk Factors
dc.subjectTime Factors
dc.subjectAdolescent
dc.subjectChild
dc.subjectArgentina
dc.subjectBrazil
dc.subjectIsrael
dc.subjectEurope
dc.subjectFemale
dc.subjectMale
dc.subjectYoung Adult
dc.subjectMaintenance Chemotherapy
dc.subjectVinorelbine
dc.titleVinorelbine and continuous low-dose cyclophosphamide as maintenance chemotherapy in patients with high-risk rhabdomyosarcoma (RMS 2005): a multicentre, open-label, randomised, phase 3 trial.
dc.typeJournal Article
dcterms.dateAccepted2019-08-19
rioxxterms.versionofrecord10.1016/s1470-2045(19)30617-5
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.licenseref.startdate2019-11
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfThe Lancet. Oncology
pubs.issue11
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 in Children and Young People
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Sarcoma Clinical Trials in Children and Young People/Sarcoma Clinical Trials in Children and Young People (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Sarcoma Clinical Trials in children and young people
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Sarcoma Clinical Trials in children and young people/Sarcoma Clinical Trials in Children and Young People (hon.)
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 in Children and Young People
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Sarcoma Clinical Trials in Children and Young People/Sarcoma Clinical Trials in Children and Young People (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Sarcoma Clinical Trials in children and young people
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Sarcoma Clinical Trials in children and young people/Sarcoma Clinical Trials in Children and Young People (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume20
pubs.embargo.termsNot known
icr.researchteamSarcoma Clinical Trials in children and young peopleen_US
dc.contributor.icrauthorChisholm, Juliaen


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