NEW YORK (Reuters Health) – When the infusion time of high-dose methotrexate (HDMTX) is shortened from 24 hours to 4 hours in cases of childhood acute lymphoblastic leukemia (ALL), less of the drug accumulates in leukemia cells, decreasing its antileukemic effects, a new study shows.
With the shorter infusion time, treatment can be given in an outpatient clinic, avoiding the need for an overnight stay. However, the new study makes a strong case against this time-saving, cost-cutting measure.
“Making changes in the administration of cancer chemotherapy so that it can be delivered more easily and perhaps cheaply in the outpatient clinic may have serious adverse consequences on treatment response,” Dr. William E. Evans, Director and CEO of St. Jude Children’s Research Hospital in Memphis, Tennessee, told Reuters Health.
The new study, he explained, was a randomized “comparative effectiveness” study to see whether such cost-cutting healthcare strategies could have adverse consequences, “and in our case it would.”
“The effect of HDMTX infusion duration has never been studied in patients with ALL,” Dr. Evans and colleagues point out in the Journal of Clinical Oncology online March 28.
The study involved 356 children with newly diagnosed ALL starting intravenous HDMTX (1 g/m²). The children were randomly assigned to receive just the first dose as either a 24-hour infusion (200 mg/m² over 5 minutes then 800 mg/m² over the next 23 hours 55 minutes) or a 4-hour constant infusion.
The clinicians found that the 24-hour infusion produced significantly higher amounts of active methotrexate polyglutamates in bone marrow leukemia cells compared to the 4-hour infusion (P = 0.0059) and “better antileukemic effects,” determined by measuring circulating ALL cells over 3 days.
Low accumulation of MTX polyglutamates in ALL cells was associated with a greater than 3-fold higher risk of relapse when compared to intermediate or high accumulation of active drug.
“For most subtypes of childhood ALL, it is best to not shorten the infusion time to avoid hospitalization, etc.,” Dr. Evans said.
An exception, the researchers note in their report, may be ALL with the t(12;21)/(ETV6-RUNX1) chromosome translocation; for this subytpe, infusion duration had no significant impact on MTX accumulation or antileukemic effect in their study.
In comments to Reuters Health, Dr. Evans emphasized that, in this study, “giving only one dose as a 4-hour infusion had no adverse consequences in our patients.” All other doses were given as a 24-hour infusion.
J Clin Oncol
