As personalized medicine has become an accepted paradigm, it may be time for oncologists to examine personalized dose levels.
In a recent article from Cancer World, the author explores the value of therapeutic drug monitoring for those receiving targeted therapies.
Therapeutic drug monitoring (TDM) is “the clinical practice of measuring specific drugs at designated intervals to maintain a constant concentration in the patient’s bloodstream, thereby optimizing individual dosage regimens. It is the clinical laboratory measurement of a chemical parameter that, with appropriate medical interpretation, will directly influence drug prescribing procedures.” 1
TDM has been recommended for imatanib to “improve efficacy, assess compliance, and evaluate drug-drug interactions.”2 It can also be an important tool in discovering any interactions GIST medications are having with medications being taken for other conditions.
A concentration of Gleevec in the blood above 1100 ng/mL correlates with better clinical outcomes according to George Demetri, MD of the Dana-Farber Cancer Institute. More on this topic can be found here.
The article suggests that poor response to drug treatment may be the result of a standard dosing approach, which does not require TDM.
There has been a ground swell of advocacy for TDM in Europe, where the European Journal of Cancer ran a series of position papers on the issue, one in particular that mentions imatinib and sunitinib among others. Read this article.
What are the roadblocks to more widespread TDM? Having access to facilities that do the testing is one. Speed of turnaround of results is another. Scheduling patients can also be a challenge, as well as the cost involved.
Regulatory barriers have also contributed to the infrequent ordering of TDM. The FDA in 2010 warned Novartis about the recommendation for therapeutic drug monitoring for imatinib, citing that there was a lack of substantial evidence or substantial clinical experience to support a correlation between patient outcome and plasma levels of imatinib.
Increased evidence is warranted to have TDM in widespread clinical use.
Plasma Level Testing
A strong advocate for TDM is Saladax Biomedical, a US company that offers assays for several targeted drugs. Saladax offers Plasma Level testing, for imatinib (Gleevec), a practice the Life Raft Group has supported.
Plasma/Blood Level Testing (BLT) is a pharmacokinetic method of determining how much imatinib (Gleevec) is present in a patient’s blood at a specific time. Typically, the minimum concentration (known as trough level or Cmin) is measured right before taking the next dose of Gleevec (ideally 22-24 hours after taking the last dose). By measuring this level doctors can see if the patient is taking their Gleevec as prescribed.
With valuable information to be obtained by the use of TDM, more studies are clearly called for. As progress is made in adapting TDM for clinical practice and in advocacy for its use, the LRG will continue to keep you posted.
1.Touw DJ, Neef C, Thomson AH, Vinks AA. Cost-effectiveness of therapeutic drug monitoring: a systemic review. Ther Drug Monit. 2005; 27:10–17.
2. Teng, JF, Mabasa, VH, Ensom. The role of therapeutic drug monitoring of imatinib in patients with chronic myeloid leukemia and metastatic or unresectable gastrointestinal stromal tumors. Ther Drug Monit. 2012; Feb;34 (1):85-97.