Individualizing Chemotherapy Dosage for Childhood ALL Based on Drug Elimination Rate

Individualizing the dosage of cancer chemotherapy can increase survival rates for children with acute lymphoblastic leukemia (ALL) without causing excessive toxicity, according to a study published in the February 18, 1998, issue of The New England Journal of Medicine.

The study, conducted 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, which affects approximately 2,500 children in the United States each year. Based on blood levels measured in each patient, clinicians adjusted the amount of medications to avoid underdosing children with fast elimination rates. This approach allows clinicians to optimize dosages based on the patient’s individual requirements 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.

Rapid Drug Elimination, Not Drug Resistance, Causes Some Relapses

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 with 182 children who were newly diagnosed with ALL. The children were randomly assigned to one of two treatment groups. One group received doses of chemotherapy drugs (methotrexate, teniposide [Vumon], and cytarabine) based on body-surface area and the other received dosages 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 anti-seizure drugs, antibiotics and anti-asthma medications, this is the first study to demonstrate that the 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.