Drug Dose Tailoring Based on Patient-Specific Factors
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Patients who have advanced breast cancer receive chemotherapy that can be just as toxic to their bodies as it is to their tumor cells. The amount of drug that circulates through the bloodstream has to be enough to kill the tumor while not killing the patient. The drug has to pass through the patient to get to the tumor! The amount of drug that reaches the tumor is affected by patient-specific factors such as the health of the liver and kidneys, proteins in the blood, age and gender. Currently the dose of drug patients receive is based solely on their "body surface area", a function of their height and weight. There is evidence that suggests this practice does not reflect the ability of the patient to process the drug. A better method of determining dose is needed.
 
 
 
 
 
 
 
 Can we predict the ability of patients to process drugs, and then prescribe chemotherapy at an individualized dose? Recent studies have shown that certain patient-specific factors, especially the amount of an important enzyme in the liver called CYP3A4, can help predict the amount of docetaxel that should be given to patients on an individualized basis. The goal of this dissertation project is to build an easy to use dosing model by analyzing this data and incorporating it into models that reflect the years of research into the metabolism of drugs. It will also explore whether there are there simple alternatives to testing for CYP3A4.
 
 
 
 
 
 
 
 The data from two studies at the Cancer Center at the University of Michigan will be examined for relationships between patient-specific factors (such as age, blood proteins, and a variety of liver enzymes) and the ability of the patient to "eliminate" or remove the drug from their bloodstream. If the drug is removed too quickly, then the current standard dose is insufficient, and if the drug is removed too slowly, the current dose is too high and therefore toxic. Statistical significance of these relationships will be determined and combined with knowledge of the movement of drug through the body gained over the last 40 years of "pharmacokinetic" (drug movement) research. The resulting models can be validated in later studies, and incorporated into chemotherapy treatment.
 
 
 
 
 
 
 
 "Pharmacogenetics" is the latest buzzword in the scientific community. This research goes beyond pharmacogenetics to use measurements of the activity of important enzymes in the body on chemotherapy agents. A biological "snapshot" is used to develop an individualized does for a specific patient. Patients given individualized doses should avoid a great deal of toxicity risk inherent in chemotherapy, and potentially benefit from increased efficacy. The modeling process to develop these dosing methods is a key step in the journey to individualized dose, and must incorporate not only statistical tools and modeling theory, but advanced expertise in the biological mechanisms at play in the movement of drugs through the body.