Individualizing Chemotherapy Dosage Improves Survival of Children With Acute Lymphoblastic Leukemia

Individualizing the dosage of cancer chemotherapy can increase survival rates for children with acute lymphoblastic leukemia (ALL) without causing excessive toxicity, according to a recent study published in The New England Journal of Medicine.

The study, by cancer specialists at St. Jude Children’s Research Hospital in Memphis, indicates that individualizing a patient’s chemotherapy dosages based on drug elimination can avoid low blood levels of anticancer medicines and thereby improve outcomes for ALL—the most common form of childhood cancer, affecting approximately 2,500 children in the United States each year. Based on blood levels measured in each patient, clinicians adjusted the amount of chemotherapeutic medications to avoid underdosing children with fast elimination. This approach allows clinicians to optimize dosages based on the patient’s individual dosage requirement rather than administering the same dosages to all children.

“In our study, patients who received individualized dosages had significantly better outcomes than those treated with conventional therapy,” said William E. Evans, pharmd, chairman of the pharmaceutical sciences department at St. Jude Hospital and one of the authors of the study.

“Our research proves that by giving different dosages to patients based on how they process drugs—quickly or slowly—rather than on body size, we can establish and maintain the level of medication needed to more effectively treat this most common type of leukemia,” Evans said.

Some Relapses Due to Rapid Drug Elimination, Not to Drug Resistance
One of the important conclusions from this study is that with conventional dosing of chemotherapy, some children relapse because their body eliminates the medications too rapidly and not because their leukemia is resistant to the chemotherapy.

The study was conducted in 182 children with newly diagnosed with ALL. The children were divided into two stratified and randomly assigned treatment groups. One group received doses of chemotherapy drugs (methotrexate, teniposide (Vumon), and cytarabine) based on body-surface area, and the other group received doses based on the rate at which they eliminate these drugs. Patients in the individualized group received fewer treatments at lower dosages and had better outcomes than patients who were treated with the conventional approach.

“While individualizing dosage based on a patient’s ability to eliminate drugs has been used with other types of medications such as antiseizure drugs, antibiotics and antiasthma medications, this is the first study to demonstrate that individualized drug dosing can be important for anticancer treatment,” said Ching-Hon Pui, MD, co-director with Dr. Evans of St. Jude Hospital’s hematological malignancies program.