For children and young adults with high-risk, B-precursor acute lymphoblastic leukemia (ALL), high-dose methotrexate resulted in fewer relapses than the standard regimen of escalating methotrexate. The results of this Phase III clinical trial were presented at the 2011 annual meeting of the American Society of Clinical Oncology.
ALL—a fast-growing cancer of the white blood cells—is the most commonly diagnosed type of leukemia in children. Each year, there are approximately 4,000 new cases of ALL diagnosed in the United States.
The chemotherapy drug methotrexate has played an important role in the treatment of ALL for several decades. In a standard approach to treatment, methotrexate is initially given at a low dose that is gradually increased based on the patient’s tolerance. The escalating methotrexate is followed by a second chemotherapy drug called asparaginase. This treatment approach is known as the Capizzi regimen.
Although current approaches to treatment provide good outcomes for many ALL patients, relapses in the central nervous system (CNS; the brain or spinal cord) continue to be a problem for some patients.
In order to determine whether a different approach to methotrexate treatment would reduce CNS relapses, researchers with the Children’s Oncology Group conducted a Phase III clinical trial among more than 2,400 patients. The study enrolled children and young adults between the ages of 1 and 30 years with newly diagnosed, high-risk, B-precursor ALL.
During the interim maintenance phase of treatment, study participants were assigned to either the standard escalating methotrexate or high-dose methotrexate. The high-dose regimen delivers a dose that is 50-times higher than the starting dose in the escalating regimen. Researchers hoped that the higher dose would be better able to reach cancer cells in the central nervous system.
- Five-year survival without a relapse was 82% among patients in the high-dose group and 75% among patients in the standard-treatment group. The high-dose treatment regimen reduced the risk of bone-marrow and CNS relapses.
- Patients in the high-dose group were less likely than patients in the standard-treatment group to experience febrile neutropenia (low white blood cell counts accompanied by fever). Rates of other significant side effects did not differ between the groups.
These results suggest that for children and young adults with ALL, high-dose methotrexate may produce better outcomes than the standard approach to treatment.
Reference: Larson EC, Walzer WL, Devidas M et al. High dose methotrexate (HD-MTX) as compared to Capizzi methotrexate plus asparaginase (C-MTX/ASNase) improves event-free survival (EFS) in children and young adults with high-risk acute lymphoblastic leukemia (HR-ALL): a report from the Children’s Oncology Group study AALL0232. Paper presented at: 2011 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2011; Chicago, IL. Abstract 3.