New data demonstrate that omitting the chemotherapy drug daunorubicin from an initial treatment regimen for children with standard-risk acute lymphocytic leukaemia (ALL) does not reduce survival outcomes, suggesting that these children may be able to achieve positive outcomes without having to endure a treatment associated with both short- and long-term toxicities.

ALL, the most common form of leukaemia in children, is a fast-growing cancer of the white blood cells in which the bone marrow makes a large number of abnormal white blood cells that are unable to develop and fight infection.

Important developments over the past 20 years have led to seminal insights about ALL in children, and today nearly 90 percent of children diagnosed with standard-risk ALL are cured. Some treatment regimens for standard-risk ALL include initial infusions of daunorubicin, a type of anthracycline.

While effective, continual use of this therapy is associated with potential long-term heart damage, leading researchers to assess whether eliminating or reducing the dosage of daunorubicin during the initial one-month induction therapy period might provide the same level of efficacy as the standard treatment protocol with reduced long-term risk.

In order to assess the efficacy of ALL treatment without daunorubicin during induction therapy, a team of researchers from 20 centers across France and one center in Belgium initiated a multicenter Phase III clinical trial in which 1,128 pediatric patients with standard-risk B-cell ALL were randomized into two treatment arms.

Arm A included 560 patients who received a standard dose of daunorubicin during induction therapy, while Arm B included 568 patients who did not receive initial therapy with daunorubicin. Both groups received doxorubicin during delayed intensification (last treatment phase before reaching maintenance) and a standard protocol of 24-month maintenance therapy from December 2000 to June 2010, during which five-year event-free survival (EFS) and overall survival (OS) were assessed.

For those patients treated with daunorubicin, the five-year EFS rate was 92.9 percent, compared to 93.3 percent in the non-daunorubicin arm. Overall survival rates were 97.2 percent and 98.2 percent in the daunorubicin and non-daunorubicin arms, respectively. Measurements of minimal residual disease, in which a small number of leukemic cells remain during treatment, were also equivalent in the two study arms. These results demonstrate similar efficacy rates of treatment strategies for standard-risk ALL that do or do not include induction treatment with daunorubicin.

“Our study data have the potential to benefit children with ALL in two important ways,” said Andre Baruchel, MD, lead author and Head of the Department of Pediatric Hematology at the Robert Debré University Hospital (Assistance Publique Hôpitaux de Paris) in Paris. “First, we now have strong evidence that reducing the amount of chemotherapy initially administered to these children, who constitute the majority of ALL patients, does not negatively affect their immediate outcome. Perhaps more importantly, we know and anticipate that removing harmful chemotherapy from their treatment can help minimize their risk of experiencing heart damage later in life.”

Source: ASH