Is Metastatic Colon Cancer Curable?

Following the introduction of 5FU in 1958, response rates for metastatic colon cancer remained in the range of 12-14 percent. After several decades, the addition of Leucovorin to 5FU improved these response rates to 20 percent. Optimal infusion schedules further enhanced responses providing objective benefits in 20-30 percent of patients. Subsequent to the introduction of Irinotecan and later Oxaliplatin, colon cancer response rates are now observed in 40-50 percent of patients — even higher in some series.

This has spawned a new interest in post-chemotherapy surgical cytoreduction. Under these circumstances, patients who present with Stage 4 disease (most often metastatic to liver) undergo aggressive combination therapy — usually Folfox-based. Those achieving substantial response (complete or partial) are then considered for partial hepatectomy to reduce residual tumor burden. In a series of trials conducted by large institutions like MD Anderson, a subset of patients is now achieving durable complete remissions using this multi-modality approach.

One example of this approach represents a novel opportunity to explore the biology of this disease.

Case Report
A 44-year-old previously healthy male presents with T3, N2, M1 colon cancer with multiple positive lymph nodes and a liver metastases. Despite the primacy of Folfox-based therapies in this setting, functional profiling of his tumor revealed superior activity for the dual modulation of Irinotecan activity with Erbitux and Avastin After several cycles of therapy, all disease had disappeared with the exception of a small residual focus in the liver.

The patient underwent a partial hepatectomy and tissue removed at the time of surgery was re-examined in the laboratory. The Ex-Vivo Analysis of Programmed Cell Death (EVA-PCD®) functional profile results had completely changed, now favoring Folfox over Irinotecan-based therapy. Following surgical recovery, the patient was provided post-operative adjuvant Folfox.

Today, more than two years since diagnosis, all biochemical and radiographic restaging reveals no evidence of disease. While the patient will require continued surveillance, he represents a genuine advance in the management of this disease and may escape recurrence. This allows him to continue a normal life, despite a diagnosis that a decade earlier would have been considered a death sentence. Cases like this will ultimately enable us to answer the question: Is metastatic colon cancer curable?

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.

One Response to Is Metastatic Colon Cancer Curable?

  1. This is a very interesting article, thanks for sharing it.

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