The goal for personalized medicine has been drummed into my head using the following mantra: selecting the right drug for the right patient at the right time. However, I have tended to avoid the use of the term personalized medicine, favoring the term targeted therapy. However and not unexpectedly, we have come to another turn in the road regarding the meaning of personalized medicine/targeted therapy medicine due to new scientific discoveries.
My goal for this note is to discuss what I will refer to as the need to cull out the un-right patient as a candidate for a particular drug therapy. A recent article in the New York Times (see: F.D.A. Urges Genetic Test Before Giving AIDS Drug) suggested this idea to me. Below is an excerpt from the article with boldface emphasis mine:
Seeking to prevent life-threatening side effects, the Food and Drug Administration is urging doctors to use a genetic test to screen patients before prescribing a drug widely used for H.I.V. infection and AIDS. In an advisory ..., the agency says that patients with a particular variation in an immune system gene should not be given the drug abacavir because they are at a far higher risk of a severe allergic reaction to the drug....F.D.A. officials said they believed that the genetic test, which is already available from some laboratories, would be quickly adopted for screening patients before prescribing abacavir....A small percentage of abacavir users suffer so-called hypersensitivity reactions, either when they start the drug or when they resume using it after some interval....Based on that data it was estimated that 61 percent of people with the genetic variant — called HLA-B*5701 — would suffer a hypersensitivity reaction, in contrast to only 4 percent without the variant, according to new information on the drug’s label.
In previous notes, I have commented at length about the use of companion diagnostics (see: Consideration of a Broader Definition for "Companion Diagnostics"; A Closer Look at Companion Diagnostics Strategies; Some Interesting Insights into Companion Diagnostics). My understanding of companion diagnostics has been that various lab tests are used to select appropriate candidates to receive a particular drug. In other words, the goal has generally been to select the patients for whom a drug will be effective. I extended this concept in another note about therapeutic efficacy (see: Moving Resources from the Therapeutic to the Diagnostic Silo) in which I suggested that molecular diagnostics and medical imaging could be used to identify those patients for whom treatment with drugs, particularly expensive chemotherapeutic agents, would be effective. It was overtly stated, however, that this approach would also enable us to cull out those patients for whom the use of a drug would not be effective. In so doing, resources could be saved.
I now understand that we need to expand our understanding and definition of personalized medicine and targeted therapy to include the selection of the right patient AND the exclusion of the un-right patient. By the use of this latter term, I mean both the patient who will not be helped by the therapy and also the patient who will be harmed by the therapy. This may seem like splitting hairs but I do like the notion of using lab testing to identify both the right and the un-right patients.
Another addition to your definition of Personalized Medicine should include "Therapeutic Drug Monitoring".
Case in point;
Chemotherapy drugs,ie. 5-fluorouracil (5-FU) are dosed by BSA. In the May 2008 issue of the Journal of Clinical Oncology, Dr E Gamelin reported a randomized multi-center study among metastatic CRC patients treated with continuous infusion 5-FU whose drug blood levels were monitored and dosing adjusted to achieve target concentrations. Gamelin demonstrated that patients were over-dosed and only 25% were actually in the optimal range. By practicing therapeutic dose management (TDM) to maintain the plasma level of 5-FU within the therapeutic window, patients did much better. They experienced significantly better objective tumor response and doubling of survival at two years, while experiencing significantly less toxicity.
Therefore, once the right patient is placed on the right therapy (genetic testing), therapeutic drug monitoring can make sure the right dose correlates with the right plasma level exposure to achieve optimal value.
Posted by: Dennis Dionne | July 25, 2008 at 03:12 PM