Doxorubicin omission feasible for select Wilms’ tumour patients

Jul 15 2015

By Lynda Williams, Senior medwireNews Reporter

Stratifying patients by histological response to preoperative chemotherapy may allow some children with Wilms’ tumour to avoid doxorubicin and its associated cardiotoxicity, suggest study findings published in The Lancet.

The phase III trial results “add to the evidence base that doxorubicin is not necessary for optimum control of stage II or III Wilms’ tumours without high-risk histological features after preoperative chemotherapy”, say Kathy Pritchard-Jones, from University College London in the UK, and co-authors.

The study included 583 children with stage II or III Wilms’ tumours who were treated with vincristine and actinomycin D before nephrectomy and had intermediate-risk disease, defined by the International Society of Paediatric Oncology classification as regressive, mixed, epithelial, stromal or focal anaplasia type tumours.

After a median of 60.8 months, 2-year event-free survival was achieved by 92.6% of patients randomly assigned to receive vincristine and actinomycin D plus doxorubicin and 88.2% of those given vincristine and actinomycin D only.

The difference between these survival rates did not exceed the predefined margin of 10%, the researchers report, and equals a number needed to treat with doxorubicin of 22 to avoid one excess relapse.

Five-year overall survival was achieved by 96.5% of patients given doxorubicin and 95.8% of those who were not.

“Although the small excess of relapses in the reduced treatment arm did not lead to a rise in the number of deaths even in the long term, a few additional children might need treatment for relapse”, the researchers say.

“More accurate prognostic risk predictors are needed, and the identification of novel molecular, histological, and clinical risk factors is a priority to allow further stratification of treatment intensity.”

In an accompanying editorial, Daniel Green, from St Jude Children’s Research Hospital in Memphis, Tennessee, USA, says the findings provoke several questions about chemotherapy use in the paediatric setting.

“[H]ow much short-term benefit in event-free survival is necessary to justify intensification of therapy in a cohort of children that, without intensification, has an excellent event-free survival rate?”, he asks.

“When is it appropriate to expose all participants of a patient cohort to a more intensive treatment regimen when the projected improvement in event-free survival is only 5–10%?”

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