Do Researchers Need Standardized Dosing for Infant Anticancer Drug Trials?

The findings:

Researchers from the Children’s Oncology Group (COG) have developed a new standardized dosing method for anticancer drugs in infants to use across all COG clinical trials. This unified method, based on dose banding and organized into tables for different drugs and dose levels, will address the limitations and variability that researchers can encounter in current methods.

Why it matters:

Doses of anticancer drugs in children are adjusted to each patient’s body surface area (BSA), which is calculated from their weight and height. However, dosing infants based on BSA causes excessive toxicity. As a result, separate dosing methods have been devised for infants. COG trials incorporate criteria to define the infant population, and methods to calculate a dose for infants based on the body weight, age, and/or BSA of each infant. The lack of a standard method has led to excessive variability across COG trials. Many of the methods also result in a big dose increase once an infant transitions into standard BSA-based dosing for children and adolescents. The new method will not just simplify and standardize infant dosing in COG trials, but also improve safety (researchers will no longer need to perform individual dose calculations) and prevent a large jump in dose as infants grow.

Who conducted the study:

Researchers from the COG Chemotherapy Standardization Task Force, including the paper’s first author Frank M. Balis, MD, director of Clinical Cancer Research in the Center for Childhood Cancer Research, Elizabeth Fox, MD, head of the Developmental Therapeutics Program, and Richard Womer, MD, pediatric oncologist at Children’s Hospital of Philadelphia, as well as researchers from the department of Pediatrics at Texas Children’s Cancer Center and the University of Texas Southwestern.

How they did it:

Dr. Balis and his colleagues analyzed infant dose modifications in 29 ongoing or recently completed COG protocols for 10 common childhood cancers. Within this wealth of data, they identified eight dose modification methods and 11 sets of milestones to define the infant population. Taking this information into account, they then used the heights and weights of 1,178 infants under 37 months of age who were previously treated on COG trials to create dosing “bands” of infants based on BSA. The study team constructed separate tables (one for each drug and dose level) that match the BSA band with a corresponding dose. The tables extend up to a BSA of 0.6 m², which is equivalent to the size of an average 3-year-old child.

Quick thoughts:

“Adopting a uniform method of dosing this special population will enhance the safety and effectiveness of anticancer drugs in infants with cancer,” Dr. Balis said.

What’s next:

Although this new infant dosing method was designed for COG protocols, it may also be applied by other clinical trial groups that study infants and young children. Next steps include determining whether the new method will help produce more uniform drug exposure across the population of infants and young children from birth to 36 months by measuring drug levels in the blood, and comparing the levels to those achieved in older children.

Where the study was published:

This study appeared in Pediatric Blood & Cancer.

Who helped fund the study:

The National Cancer Institute, St. Baldrick’s Foundation, and Alex’s Lemonade Stand Center of Excellence Award supported the study.

Where to learn more:

You can read the study and view supplemental figures online and learn more about determining appropriate dosing for anticancer drugs at our main hospital website.