Scientifically-based Functional Profile Under Fire

Winston Churchill once said, “Democracy is the worst form of government, except for all the others that have been tried.” I am reminded of this quote by a “conversation” that recently took place on a cancer patient forum.

A patient wrote that they had requested that tissue be submitted for sensitivity analysis and their physician responded by describing this work as a scam. A scam is defined by the American Heritage Dictionary as slang for a “fraudulent business scheme.”

Continuing Churchill’s thread, we might respond, “that laboratory directed therapies are the worst form of cancer therapy, except for all the others that have been tried.”

Using functional profiling we measure the effect of drugs, radiation, growth factor withdrawal and signal transduction inhibition upon human tumors. Using our extensive database we compare the findings with the results of similar patients – by diagnosis and treatment status – to determine the most active and least toxic drug or combination for each patient.

The test isn’t perfect. Some patient’s cancer cells (about 5 – 7 percent of the time), do not survive the transport and processing, so no assay can be performed at all. Some patients are resistant to all available drugs and combinations. And finally, based on the established performance characteristics of the test, we can only double or in some circumstances triple, the likelihood of a clinical response.  This is all well documented in the peer-reviewed literature.

Despite this, it appears that in the eyes of some beholders these strikingly good results constitute a “scam.” So let us, in the spirit of fairness, and academic discourse examine their results.

First, it must be remembered that today in 2012 only a minority of cancer patients actually show objective response to available cancer therapies. Five-year survivals, the benchmark of success for advanced disease in oncology (those whose disease has spread beyond the primary site), have not changed in more than five decades.

The highly lauded clinical trial process, according to a study from the University of Florida, only provides a better outcome for a new drug over an old one, once for every seven clinical trials conducted

More disturbing, only one out of 14 clinical trials provide a survival advantage of 50 percent or greater for the successful treatment group.

According to a study from Tuft’s University, it takes 11 years and more than $1,000,000,000 dollars for a new drug to receive FDA approval.

And in a study published in the New England Journal of Medicine only 8 percent of drugs that complete Phase I (safe for human use) ever see the light of day for clinical therapy. This is the legacy of NCCN-guided, University-approved, ASCO-authorized clinical therapeutics programs to date.

As a practicing medical oncologist I am only too familiar with the failings of our modern clinical trial system. Having witnessed the good outcomes of our own patients on assay-directed protocols whose benefits derive from the intelligent use of objective laboratory data for the selection of chemotherapy drugs, I for one will NEVER return to business-as-usual oncology, regardless of what moniker the naysayers might choose to attach to this approach.

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.

2 Responses to Scientifically-based Functional Profile Under Fire

  1. patmerwin says:

    Dr. Nagourney, as a “victim” of your “scam” who is has been in complete remission from metastatic lung cancer for four years, I am beyond greatful that I didn’t end up with a “business as usual” oncologist.

    The real scam is that patients are led to believe that “standard care” is the same as “best” when it clearly isn’t even “better”. How very sad for those victims of “business as usual”. 😦

  2. It seems to me, going after a surgical/biopsy specimen has a role in eliminating ineffective agents and avoid unnecessary toxicity and in directing “correct” therapy. Data has shown that patients benefit both in terms of response and survival from drugs and drug combinations found to be “active” in assays even after treatment failure with several other drugs, many of which are in the same class, and even with combinations of drugs found to have low or no activity as single agents but which are found in the assay to produce a synergistic and not merely an additive anti-tumor effect. There would be a huge advantage to the patient to receive a “positive/sensitive” drug, compared to a “negative/resistant” drug.

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