Giving children with relapsed acute lymphoblastic leukaemia (ALL) the chemotherapy drug mitoxantrone can significantly improve survival rates compared with standard therapy, newly released trial results indicate.

In an open-label randomised clinical study conducted at 22 centres in the UK and Ireland and nine in Australia and New Zealand, overall survival after three years was 45.2% in children taking the standard therapy, idarubicin, and 69.0% in those given mitoxantrone. For the primary endpoint, progression-free survival, three-year rates were 35.9% for idarubicin and 64.6% for mitoxantrone.

The results were simultaneously presented at the American Society of Hematology annual meeting in Orlando, US and published in The Lancet. In an accompanying editorial, Dr Martin Schrappe of University Medical Centre Schleswig-Holstein in Germany said the survival advantage with mitoxantrone over idarubicin was one of the largest ever seen with a single treatment modification. Moreover, toxic treatment effects were less frequent in the mitoxantrone than in the idarubicin group.

The ALL R3 trial was funded by Cancer Research UK and Leukaemia & Lymphoma Research in the UK and by Cancer Council NSW and Sporting Chance Cancer Foundation in the other countries. Recruitment for the study began in 2003 and randomisation was halted in December 2007 due to the marked differences in progression-free and overall survival between the mitoxantrone and the idarubicin groups.

A total of 216 patients aged one to 18 years with first relapse of acute lymphoblastic leukaemia were stratified into high-, intermediate- and standard-risk groups and were randomised to either idarubicin or mitoxantrone. After three blocks of therapy, all high-risk patients and those from the intermediate-risk group with post-induction high minimal residual disease received an allogenic stem-cell transplant.

“As a result of this trial, mitoxantrone is now the standard treatment for relapsed ALL, and is having a significant impact on the number of children who beat the disease worldwide,” commented Professor Vaska Saha, lead study author and a Cancer Research UK paediatric oncologist based at the Paterson Institute in Manchester.

“This is the first time that a trial in ALL has been stopped so early after one drug had such clear benefits for patients,” Saha added.

While the number of children surviving ALL has risen from 50% to more than 80% over the past 30 years, similar improvements have not been seen in children whose cancer returns, Cancer Research UK pointed out. ALL remains the leading cause of cancer death in children and until now the survival rate in relapsed patients was constant at around 50%.