As the day shortens and the air cools we are reminded, by the first fall beauty, that long gone are the dog days of summer as the leaves change into a colorful panorama. October is also the month many websites and stores turn pink to call attention once again to our great enemy cancer, specifically Breast Cancer.
In the 1970s, those involved in Therapeutic Drug Monitoring (TDM) began advocating for routine TDM of antineoplastic drugs. Methotrexate TDM was demonstrated to be clinically significant in leukemia management. When the methotrexate levels became too high, the patient could be “rescued” from potentially harmful methotrexate toxicity by administering Leucovorin. Analytical assays for monitoring several antineoplastic drugs utilized at that time were developed.
Unfortunately, clinical oncologists did not recognize or accept the value of TDM. The main reason cited was they treated with a cocktail of drugs and did not believe measuring one drug in a cocktail would provide useful clinical management information. Decades later, following a series of disturbing studies indicating the cocktails and dosages they utilized in cancer treatment did not even begin to reach those levels necessary kill certain cancer types. One study demonstrated 60% of patients treated with recommended dosages of 5-fluorouracil (5-FU) to control colon cancer never reached 5-FU levels sufficient to kill the cancer cells. The patient’s cancer continued to grow even with the recommended therapy. The clinical outcome was often a fatal drug failure. (J Clin Oncol 1998; 16:1470-1478, J Clin Oncol 2008; 26:2099-2105, J Clin Oncol 2008; 26:2078-2079)
Dr. William Evans and his colleagues at St. Jude’s Children’s Hospital clearly demonstrated the value of TDM in childhood acute lymphocytic leukemia (ALL). Over a period of 10 years, without any new drugs to treat ALL marketed, they increased the survival rate of their patients from 50% to 90% simply by monitoring the anti-neoplastic drug concentrations and regulating the patient dosages appropriately. Just as importantly, the number of patients showing adverse drug effects decreased significantly. It is to be noted these patients were receiving multiple anti-neoplastic drugs in various cocktails. (Clin Chem 1998; 44:2 388–400, N Engl J Med 2006; 354:166-78).
The American Cancer Society has recently begun to emphasize the importance of not only finding the multiple causes of cancers; but, also finding new techniques to prevent or minimize cancer growth. TDM is a currently available technique which can be utilized to achieve that goal. By monitoring a patient’s anti-neoplastic levels it is possible to ensure the optimal amounts are present to destroy the cancer. At the same time, TDM can be utilized to minimize or prevent anti-neoplastic drug toxicity simply by the appropriate dosage adjustments. For example, we know monitoring busulfan concentrations to optimize dosages decreases (prevents) the risk of bone marrow rejections.
TDM is not the panacea for eradicating and preventing cancer. Rather, it is a powerful tool available NOW to aid oncologists in managing various cancer types. If you or your loved ones developed cancer today, you would want the most advanced and safest treatment available. Using today’s advanced analytical techniques; TDM is one of the most powerful tools available to prevent cancer growth and antineoplastic drug side effects. Anti-neoplastic TDM is one (but, not the only) way to prevent many of the adverse outcomes commonly associated with chemotherapy.