Optimal Duration of Preoperative Therapy in Unilateral and Nonmetastatic Wilms’ Tumor in Children Older Than 6 Months: Results of the Ninth International Society of Pediatric Oncology Wilms’ Tumor Trial and Study

Tournade, M F; Com-Nougué, C; Kraker, Jan de; Ludwig, R.; Rey, Annie; Burgers, J M; Sandstedt, Bengt; Godziński, Jan; Carli, Modesto; Pötter, Richard; Zucker, J. M.

doi:10.1200/jco.2001.19.2.488

Cited by 253 publications

(188 citation statements)

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“…17 All other countries continued the well established SIOP approach of starting preoperative chemotherapy on the basis of clinical and imaging characteristics consistent with a diagnosis of Wilms' tumour, combined with measuring urinary catecholamines to exclude neuroblastoma, and reserving biopsy for cases with diagnostic dilemma. 2,18,19 Three-dimensional tumour volume was recorded at diagnosis and after completion of preoperative chemotherapy, according to whichever imaging method had been applied (ultrasonography, CT scan, or MRI scan). The calculated volume showed close correlation between methods (appendix).…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2015

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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 g/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 eventfree 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 (<1%) of 291 receiving treatment including doxorubicin died of sepsis, three (1%) of 292 receiving treatment excluding doxorubicin died of varicella, metabolic seizure, and sepsis during treatment for relapse. 17 patients (3%) had hepatic veno-occlusive disease. Cardiotoxic effects were reported in 15 (5%) of 291 children receiving treatment including doxorubicin. 12 children receiving treatment including doxorubicin, and ten children receiving treatment excluding doxorubicin, died, with the remaining deaths from tumour recurrence.

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Section: Methodsmentioning

confidence: 99%

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

et al. 2015

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“…Approximately two-thirds of patients with Wilms tumour now receive chemotherapy consisting of only two drugs, actinomycin D and vin cristine 11 . Other patients, including those with metastatic disease and high-risk histological subtypes, are believed to benefit from doxorubicin [12][13][14][15][16] . Moreover, as inno vative techniques emerge, surgical and radiotherapeutic procedures are improving.…”

Section: Treatment Recommendationsmentioning

confidence: 99%

“…Similar to the SIOP−2001 protocol, the UMBRELLA protocol continues to recommend preoperative actinomycin D and vincristine for patients newly diagnosed with Wilms tumour aged ≥6 months, based on results of previous SIOP trials that showed tumour downstaging using this regimen 2,6,8,9,14,17 . This benefit was also independently observed in the randomized, controlled UKW3 trial conducted by the UK Children's Cancer and Leukaemia Group (UKCCLG, previously known as the UK Children's Cancer Study Group) 18 .…”

Section: Treatment Recommendationsmentioning

confidence: 99%

Rationale for the treatment of Wilms tumour in the UMBRELLA SIOP–RTSG 2016 protocol

et al. 2017

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“…Children with a Wilms tumor were treated with preoperative chemotherapy, followed by a nephrectomy, systemic chemotherapy and when necessary with local radiation therapy, according to SIOP protocols 9 and 93-01 (D 'Angio, 1983;Tournade et al, 2001). Children with a Wilms tumor did not receive CNS-directed treatment.…”

Section: Research Participants and Treatment Protocolsmentioning

confidence: 99%

Visuomotor control in survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only

Buizer

Sonneville

Heuvel‐Eibrink

et al. 2005

J. Inter. Neuropsych. Soc.

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Treatment for childhood acute lymphoblastic leukemia (ALL), which includes CNS prophylaxis, is associated with central and peripheral neurotoxicity. The purpose of the present study was to analyze the effects of chemotherapy on various levels of visuomotor control in survivors of childhood ALL treated without cranial irradiation, and to identify risk factors for possible deficits. Visuomotor function was compared between children after treatment for ALL (n 5 34), children after treatment for Wilms tumor, which consists of non-CNS directed chemotherapy (n 5 38), and healthy controls (n 5 151). Three tasks were administered: a simple visual reaction time task and two tasks measuring visuomotor control with one requiring a higher level of cognitive control than the other. Visuomotor deficits were detected only in the ALL group, with poorer performance restricted to the condition requiring the highest level of control. Significant risk factors for poorer performance were female gender and a short time since end of treatment, and a trend was found for a young age at diagnosis. A high cumulative methotrexate dose was an adverse predictive factor in girls. The results indicate that chemotherapy-induced central neurotoxicity in childhood ALL treatment is associated with higher order visuomotor control deficits. Girls appear to be particularly vulnerable. (JINS, 2005, 11, 554-565.)

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Optimal Duration of Preoperative Therapy in Unilateral and Nonmetastatic Wilms’ Tumor in Children Older Than 6 Months: Results of the Ninth International Society of Pediatric Oncology Wilms’ Tumor Trial and Study

Abstract: The 4-week schedule pre-nephrectomy chemotherapy regimen should be considered the standard treatment. Clinical trials should continue to improve the cure rate of high-risk patients and the quality of life of children with a more favorable prognosis.

Cited by 253 publications

References 19 publications

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

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

Rationale for the treatment of Wilms tumour in the UMBRELLA SIOP–RTSG 2016 protocol

Visuomotor control in survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only

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