When it Works, it Works

Despite the toxicities and haphazard administration schedules associated with many chemotherapy combinations, some patients have dramatic responses to therapy. One such patient was seen in consultation today. In September 2009, this 46-year-old gentleman presented with bilateral plural effusions associated with bilateral pulmonary infiltrates, mediastinal adenopathy, ascite, and respiratory failure. He was immediately intubated and stabilized.

His condition was so grave that no one wished to give him any therapy. A medical oncologist consulted and examined the patient’s extremely poor performance status. I was then asked to provide a second opinion. After discussing the findings with the primary oncologist, we agreed to try empiric chemotherapy with a combo known as folfox. Our reasoning was that this young man with adenocarcinoma would stand the greatest chance of benefit from platinum based therapy and that 5FU — though not often used in lung — would have activity both in thoracic and gastrointestinal primaries. This highly undifferentiated neoplasm could not be better characterized to identify a likely site of origin.

Contrary to everyone’s expectations, the patient had a dramatic recovery. He was first weaned off the respirator, then transferred to physical therapy and, finally, discharged for follow up and out patient chemotherapy. Now, seven months later, the patient is back to normal activities. In my discussions with this patient, I suggested he remain on therapy and I made no recommendation that changes or biopsies be considered. It is my belief that this patient is a biological responder. His underlying disease retains the capacity to respond to therapy. For this reason, I encourage the patient to follow up if he shows signs of progression. It is very possible that other classes of drugs can yet provide benefit when necessary. My reasoning is that the patient has a tumor that retains programmed cell death capacity. The selection of therapies in the future may well continue his excellent response. Nonetheless, I would not intervene at this time based on the old saying that “if it isn’t broken, don’t fix it.” My final point in this patient, despite my misgivings about randomly administering therapies, is that cancer therapies can be extremely effective and well tolerated. Our job is to match the most active, least toxic drugs for each patient.

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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