Pharmacogenetic cancer test receives FDA clearance
diagnostic to a specific drug therapy has been approved by the FDA.
The test represents a new area of pharmacogenomics in which
molecular diagnostic and drug pairings emerge as a preferred
Pharmacogenetics is the discipline that examines the genetic basis for individual variations in response to therapeutics. Pharmacogenetics promises to develop individualised medicines tailored to patients' genotypes. However, identifying and genotyping a vast number of genetic polymorphisms in large populations poses a great challenge.
The genetic test detects a change in the DNA of a gene that encodes for a protein involved in the metabolism of the chemotherapy drug Camptosar (irinotecan). The test gives scientists advance knowledge of the individual risk for toxicity from Camptosar.
As a result, scientists are able to tailor this chemotherapy regimen to the individual, thus reducing toxicity.
Camptosar is used to treat colorectal cancer and was relabelled recently to include dosing recommendations based on a patient's genetic profile.
Third Wave Technologies' Invader UGT1A1 test could provide colorectal cancer patients with significant medical benefit. Approximately 150,000 new cases of colorectal cancer are diagnosed each year in the United States.
"The selection of the right dose is one of the greatest challenges in the treatment of cancer patients," said Howard McLeod, professor of oncology at Washington University School of Medicine.
"The recent expansion of available therapies for colorectal cancer has made toxicity avoidance an important aspect of the clinical decision," he added.
In recent years, it has become increasingly apparent that dozens of human drug metabolism polymorphisms exist. The interindividual variability in drug metabolism that is caused by these polymorphisms do not represent relatively large differences of 10-fold to greater than 1000-fold.
When attributed to a single gene, dramatic differences in drug metabolism can be seen, even among family members. In addition, there are chronic effects. Over a patient's lifetime, differences in the metabolism of drugs and environmental substances can lead to interindividual differences in the buildup of DNA damage, leading to toxicity or tumourigenesis.
According to a Nuffield Council report, common treatments for conditions including diabetes, depression and asthma are only effective in around 60 per cent of patients. Medicines used to treat cancer may have a figure as low as 25 per cent.
June 2003 saw the launch of the first ever diagnostic test by the Swiss drugs company Roche. Its product was designed to identify common genetic variations that effect people's ability to metabolise widely used classes of drugs.
The launch of the product, AmpliChip CYP450, led to excited estimates of a burgeoning market for pharmacogenetic products. A Roche press release predicted an annual market of $100m (£60m; €87m) by 2008 for this one test alone.
"While the pharmacogenetic market is just beginning to emerge, we believe it will become increasingly valuable," said John Puisis, president and chief executive officer of Third Wave.
"Our goal is to ensure that Third Wave is well positioned to capture that value as the market develops and molecular diagnostic and drug pairings continue to be identified, as we expect they will be."