Tailoring cancer drug dosage

Scientists from Flinders University are collaborating with clinicians from Flinders Medical Centre to make a class of cancer drugs more effective by allowing patients to receive the dose that is best for them. It is hoped that the research will combat the varying reactions and side effects experienced by different patients despite receiving the exact same doses of medication.

In a two-year study, funded by a $75,000 grant from biomedical research charity the Ramaciotti Foundation, the team will use a computer-modelling technique called physiologically based pharmacokinetic (PBPK) modelling to measure the amount of drugs in a person’s blood, then tailor the dose depending on individual needs.

They will investigate a class of anticancer drugs called tyrosine kinase inhibitors (TKIs), used to treat cancers that are unresponsive to chemotherapy, such as renal, liver and some lung cancers. While other cancer drugs are prescribed at a fixed dose because they produce relatively similar results, TKIs are best given at a specific dose to have an optimum effect - yet Chief Investigator Dr Andrew Rowland says this is usually not the case.

“At the moment everyone gets the same dose but, because every reaction is different, some people take longer to expel the drug, which means they get more side effects than someone who metabolises the drug too quickly, in which case the drug might not work at all,” Dr Rowland said. Despite these variances, TKIs have not yet been studied extensively.

PBPK modelling will be used to take data from a small patient sample to predict the absorption and excretion of different TKIs doses in a larger population. As TKIs are not widely used at the moment, Dr Rowland said it quite difficult to get enough patients for drug optimisation research.

He added that it would be unethical to change the dosage in real cancer patients without knowing the consequences, “but the computer simulation will allow us to determine the effect of dose adjustments on a larger population, based on data from real people”.

He said the research could eventually be applied to other drugs to improve delivery and efficiency.