Initial results from a clinical trial have shown that high-dose methotrexate may be superior to standard, low-dose regimens without increasing toxicity for children and young adults with high-risk B-acute lymphoblastic leukemia (ALL).
For decades, patients with ALL have been treated with a combination of steroids and methotrexate, along with other supporting agents. Patients considered at high risk of relapse—those with high white blood cell counts or aged 10 years or older—are also treated with methotrexate, but treatment is administered in a gradual escalating dosage. In a study led by Eric C Larsen, MD, Maine Children’s Cancer Program (Scarborough), investigators reported the early results of a clinical trial evaluating two alternative treatment interventions for high-risk patients with ALL.
A total of 3154 patients with high-risk ALL were enrolled in the trial between January 2004 and January 2011. Participants were then randomly assigned to receive either dexamethasone or prednisone during induction, and either high-dose methotrexate or Capizzi escalating-dose methotrexate plus pegaspargase, a common chemotherapy drug, during the interim maintenance 1 phase of treatment.
Overall, investigators found that both patient groups responded well to treatment. At initial monitoring, the observed 5-year event-free survival rate of patients treated with high-dose methotrexate was superior to that of patients treated with escalating-dose methotrexate (82% vs 75.4%). That rate fell slightly when final data were recorded, but was still significantly higher in the high-dose group (79.6%) than in those treated with the escalating dose (75.2%). In addition, high-dose methotrexate seemed to decrease the risk of bone marrow and central nervous system recurrences.
The addition of dexamethasone to high-dose methotrexate treatment also produced the best 5-year event-free survival rate in patients aged 1 to 9 years compared with the 3 other treatment combinations. However, patients aged 10 years and older did not seem to benefit from dexamethasone and experienced higher rates of osteonecrosis.
Researchers concluded that high-dose methotrexate is superior to Capizzi methotrexate for the treatment of high-risk ALL without any significant increase in toxicity. Further, dexamethasone administered during induction may also benefit younger patients.
