Anticancer drugs are dosed in children based on the child’s body surface area, which is calculated from the weight and height, or simply on the body weight. These measures of body size do not account for variation in the ability of the liver and kidneys to eliminate the drug from the body.
The rate of drug elimination by the kidneys and liver determines the amount of drug exposure in the body and in the tumor. A number of factors can influence the function of these organs and alter the rate of drug elimination. As a result, the severity of drug toxicity and response of the cancer to treatment is often variable and unpredictable.
Anticancer drug doses are often adjusted in children who experience a severe toxicity. More accurate dosing methods that result in more uniform drug exposure in the body could improve the safety and effectiveness of these drugs.
At the Center for Childhood Cancer Research, Frank M. Balis, MD, Elizabeth Fox, MD, and researchers are developing new approaches to individualize the dose of anticancer drugs for children. Rather than relying on body surface area or weight to calculate the dose, specific biomarkers that accurately reflect kidney function and drug metabolizing capacity are being identified. If these biomarkers can predict the drug exposure in the body, then they can be used to calculate an individualized dose that will provide more uniform, predictable drug exposures, and lower the risk of severe toxicity, while ensuring adequate drug exposure to treat the cancer.