When to Use Assay Testing

There is a common misconception that chemosensitivity-resistance assays are only useful for patients in the relapsed state once they have failed conventional first line therapy. This assertion is wrong on several levels.

  1. First, the best outcomes in cancer medicine are known to occur with first line therapies. The selection of the most active, least toxic drug or combination should be the goal of every physician at the time of initial therapy. As CSRAs have well established performance characteristics (sensitivity and specificity), their positive predictive accuracy (the likelihood that a patient with a sensitive assay will respond to the clinical treatments selected) are highest when they are applied in the first line setting.
  2. Secondly, on theoretical grounds, exposure to randomly selected chemotherapeutics, many of which are mutagens, may select for or induce drug resistance, diminishing the likelihood of a good outcome in second line or subsequent therapy.
  3. Finally, the introduction of active targeted agents provides patients the opportunity to receive first line therapies that do not carry the side effects and toxicities of classic cytotoxic chemotherapies. Our experience with first line Erlotinib in non-small cell lung cancer today provides response rates that exceed those associated with patients selected based on EGFr mutation or overexpression. Furthermore, the selection of candidates for combined targeted agents, e.g. EGFR & VEGF inhibitors, etc. provides a growing opportunity to introduce novel combinations into the first line setting. The growing cost and potential toxicity of some of these agents make the application of accurate selective methodologies increasingly crucial.

First line chemotherapy provides patients their best opportunity for a good outcome. There is no rationale for exposing patients to randomly selected toxic and potentially ineffective therapy when clinically validated selective methodologies can be applied in the first line as well as second line setting and beyond.

About Dr. Robert A. Nagourney
Dr. Nagourney received his undergraduate degree in chemistry from Boston University and his doctor of medicine at McGill University in Montreal, where he was a University Scholar. After a residency in internal medicine at the University of California, Irvine, he went on to complete fellowship training in medical oncology at Georgetown University, as well as in hematology at the Scripps Institute in La Jolla. During his fellowship at Georgetown University, Dr. Nagourney confronted aggressive malignancies for which the standard therapies remained mostly ineffective. No matter what he did, all of his patients died. While he found this “standard of care” to be unacceptable, it inspired him to return to the laboratory where he eventually developed “personalized cancer therapy.” In 1986, Dr. Nagourney, along with colleague Larry Weisenthal, MD, PhD, received a Phase I grant from a federally funded program and launched Oncotech, Inc. They began conducting experiments to prove that human tumors resistant to chemotherapeutics could be re-sensitized by pre-incubation with calcium channel blockers, glutathione depletors and protein kinase C inhibitors. The original research was a success. Oncotech grew with financial backing from investors who ultimately changed the direction of the company’s research. The changes proved untenable to Dr. Nagourney and in 1991, he left the company he co-founded. He then returned to the laboratory, and developed the Ex-vivo Analysis - Programmed Cell Death ® (EVA-PCD) test to identify the treatments that would induce programmed cell death, or “apoptosis.” He soon took a position as Director of Experimental Therapeutics at the Cancer Institute of Long Beach Memorial Medical Center. His primary research project during this time was chronic lymphocytic leukemia. He remained in this position until the basic research program funding was cut, at which time he founded Rational Therapeutics in 1995. It is here where the EVA-PCD test is used to identity the drug, combinations of drugs or targeted therapies that will kill a patient's tumor - thus providing patients with truly personalized cancer treatment plans. With the desire to change how cancer care is delivered, he became Medical Director of the Todd Cancer Institute at Long Beach Memorial in 2003. In 2008, he returned to Rational Therapeutics full time to rededicate his time and expertise to expand the research opportunities available through the laboratory. He is a frequently invited lecturer for numerous professional organizations and universities, and has served as a reviewer and on the editorial boards of several journals including Clinical Cancer Research, British Journal of Cancer, Gynecologic Oncology, Cancer Research and the Journal of Medicinal Food.

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