Omission of doxorubicin from the treatment of stage II-III, intermediate-risk Wilms' tumour (SIOP WT 2001): an open-label, non-inferiority, randomised controlled trial
| Autor: | Kathryn Pritchard-Jones, Anne-Sophie DEFACHELLES, Sucheta Vaidya, Gustaf Ljungman, Norbert Graf, Marc Ansari, Gordan Vujanic, Ricardo López Almaraz, Pedro Zubizarreta, Jan Godziński, Pamela Kearns, Anna Llort, Beatriz De Camargo, Leo Kager, Harm Van Tinteren, Ingrid Øra |
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| Přispěvatelé: | University of Zurich, Pritchard-Jones, Kathy, CCA -Cancer Center Amsterdam, Radiotherapy, Paediatric Oncology, Oncogenomics |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Vincristine Adolescent medicine.medical_treatment Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use 610 Medicine & health Kaplan-Meier Estimate 2700 General Medicine Nephrectomy Wilms Tumor Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Doxorubicin Child Kidney Neoplasms/drug therapy/pathology/surgery Neoplasm Staging Neoadjuvant Therapy/adverse effects/methods Chemotherapy Cardiotoxicity ddc:618 Intention-to-treat analysis business.industry Standard treatment Infant Wilms' tumor General Medicine Doxorubicin/administration & dosage/adverse effects medicine.disease Kidney Neoplasms Neoadjuvant Therapy Surgery Regimen Treatment Outcome Wilms Tumor/drug therapy/pathology/surgery Chemotherapy Adjuvant 10036 Medical Clinic Child Preschool Dactinomycin Chemotherapy Adjuvant/adverse effects/methods Dactinomycin/administration & dosage/adverse effects Female Vincristine/administration & dosage/adverse effects business medicine.drug |
| Zdroj: | Pritchard-Jones, K, Bergeron, C, de Camargo, B, van den Heuvel-Eibrink, M M, Acha, T, Godzinski, J, Oldenburger, F, Boccon-Gibod, L, Leuschner, I, Vujanic, G, Sandstedt, B, de Kraker, J, van Tinteren, H, Graf, N & SIOP Renal Tumours Study Group 2015, ' Omission of doxorubicin from the treatment of stage II-III, intermediate-risk Wilms' tumour (SIOP WT 2001) : an open-label, non-inferiority, randomised controlled trial ', Lancet, vol. 386, no. 9999, pp. 1156-1164 . https://doi.org/10.1016/S0140-6736(14)62395-3 Lancet, 386(9999), 1156-1164. Elsevier Limited The Lancet, Vol. 386, No 9999 (2015) pp. 1156-64 |
| ISSN: | 0140-6736 |
| DOI: | 10.1016/s0140-6736(14)62395-3 |
| Popis: | BACKGROUND: Before this study started, the standard postoperative chemotherapy regimen for stage II-III Wilms' tumour pretreated with chemotherapy was to include doxorubicin. However, avoidance of doxorubicin-related cardiotoxicity effects is important to improve long-term outcomes for childhood cancers that have excellent prognosis. We aimed to assess whether doxorubicin can be omitted safely from chemotherapy for stage II-III, histological intermediate-risk Wilms' tumour when a newly defined high-risk blastemal subtype was excluded from randomisation.METHODS: For this international, multicentre, open-label, non-inferiority, phase 3, randomised SIOP WT 2001 trial, we recruited children aged 6 months to 18 years at the time of diagnosis of a primary renal tumour from 251 hospitals in 26 countries who had received 4 weeks of preoperative chemotherapy with vincristine and actinomycin D. Children with stage II-III intermediate-risk Wilms' tumours assessed after delayed nephrectomy were randomly assigned (1:1) by a minimisation technique to receive vincristine 1·5 mg/m(2) at weeks 1-8, 11, 12, 14, 15, 17, 18, 20, 21, 23, 24, 26, and 27, plus actinomycin D 45 μg/kg every 3 weeks from week 2, either with five doses of doxorubicin 50 mg/m(2) given every 6 weeks from week 2 (standard treatment) or without doxorubicin (experimental treatment). The primary endpoint was non-inferiority of event-free survival at 2 years, analysed by intention to treat and a margin of 10%. Assessment of safety and adverse events included systematic monitoring of hepatic toxicity and cardiotoxicity. This trial is registered with EudraCT, number 2007-004591-39, and is closed to new participants.FINDINGS: Between Nov 1, 2001, and Dec 16, 2009, we recruited 583 patients, 341 with stage II and 242 with stage III tumours, and randomly assigned 291 children to treatment including doxorubicin, and 292 children to treatment excluding doxorubicin. Median follow-up was 60·8 months (IQR 40·8-79·8). 2 year event-free survival was 92·6% (95% CI 89·6-95·7) for treatment including doxorubicin and 88·2% (84·5-92·1) for treatment excluding doxorubicin, a difference of 4·4% (95% CI 0·4-9·3) that did not exceed the predefined 10% margin. 5 year overall survival was 96·5% (94·3-98·8) for treatment including doxorubicin and 95·8% (93·3-98·4) for treatment excluding doxorubicin. Four children died from a treatment-related toxic effect; one (INTERPRETATION: Doxorubicin does not need to be included in treatment of stage II-III intermediate risk Wilms' tumour when the histological response to preoperative chemotherapy is incorporated into the risk stratification.FUNDING: See Acknowledgments for funders. |
| Databáze: | OpenAIRE |
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