The New York Times had a great article a couple of days ago on the need for personalized medicine to become more than a catchy phrase.
As we're learning more about the interaction between genes and drug metabolism, we're also learning that large numbers of people are either taking the wrong drug or taking drugs that won't work.
Researchers have known for some time that genetic variants determine how well drugs work. Some versions of a gene cause a drug to be metabolized faster, some slower, and when combined, at an intermediate rate. In the simplest case, the slow metabolizers might be getting too much of a drug, and the fast metabolizers too little. Sometimes the drug won't work in people with the wrong genotype, and sometimes the wrong drug is lethal.
Too little education?
Despite this knowledge, there's been a delay putting it into practice. One problem is education. The genetic tests are appearing quite rapidly, leaving physicians with little time to catch up.
According to Steve Murphy (The Gene Sherpa), who adds: "I see that lawsuit creeping closer and closer":
â¢Only 17% of patients with familial colon cancer risk were referred to appropriate genetic counseling according to a study at Harvard.
â¢Prenatal counseling is not offered to 9 of 10 women who meet indications!
â¢Only 37% of MDs know that BRCA genes can be passed by the father!
And from the NYT:
Moreover, doctors do not always conduct the tests or follow the results. The big insurer UnitedHealthcare found in 2005 that 8 percent of the women getting the drug had tested negative for the required genetic characteristic. An additional 4 percent had not been tested at all, or their test results could not be found.
Too little time?
There are also delays in translating information from the research lab to the clinical world. Researchers may know that a certain version of a gene will affect metabolism, but the implications for changing treatment aren't always clear. Clinical trials could answer those questions, but they are expensive and would likely increase drug costs.
Presently, there are only a few drugs with genotyping recommendations on their labels. Earlier this month, the FDA met to discuss modifying the label information for additional drugs. Some of the drugs under consideration are Erbutix and Vectibix, used to treat colon cancer. According to the NYT, these drugs are ineffective for 40 percent of patients with certain tumor genotypes.
Are patients losing patience?
Whatever happens, it seems that increasing the use of genetic information in drug prescribing can't come soon enough for many patients, especially women who've had breast cancer.
The NYT described a study at the Mayo Clinic where:
In the case of tamoxifen, Dr. Matthew P. Goetz of the Mayo Clinic and colleagues went back to an old trial and used stored tumor samples to test the 2D6 genes of each patient. The researchers reported in 2005 that 32 percent of the women with inactive 2D6 enzyme had relapsed or died within two years, in contrast to only 2 percent of the other women.
In other words, the dead women might have done okay, if they'd had a different drug.
From the NYT:
For more than two years, Jody Uslan had been taking the drug tamoxifen in hopes of preventing a recurrence of breast cancer. Then a new test suggested that because of her genetic makeup, the drug was not doing her any good.
"I was devastated," said Ms. Uslan, 52, who stopped taking tamoxifen and is now evaluating alternative treatments. "You find out you've been taking this medication for all of this time, and find out you are not getting any benefit."
Andrew Pollack, December 30, 2008, Patient's DNA May Be Signal to Tailor Medication, The New York Times.