There is More to Gastrointestinal Cancer Management Than FOLFOX

Several months ago, I was introduced to a 58-year-old gentleman with a very bad diagnosis — a bout of gastrointestinal bleeding that had lead to an upper GI endoscopy. It wasn’t an ulcer, or even gastric cancer, but a very rare form of cancer arising in the duodenum. Adenocarcinoma of the duodenum is very uncommon.

This patient was in trouble.

In addition to the bleeding, he had lost a substantial amount of weight, was in pain and had a very large tumor that was nearly obstructing his upper GI tract. After getting the patient stabilized in September 2010, he was referred to a surgeon who conducted an aggressive surgical resection. The recovery was difficult, prolonged and accompanied by additional GI bleeding. By the time the patient had recovered adequately enough to consider additional therapy, his PET scan revealed extensive re-growth.

If you were to ask medical oncologists in the United States what to give such a patient, 99 percent would recommend FOLFOX or some variation thereof. But, FOLFOX wasn’t the right treatment for this patient. Instead, he had a strong signal for Irinotecan, which was further enhanced by the addition of an EGFR inhibitor. Based on this, I elected to treat the patient with Erbitux + Irinotecan. Before starting therapy, his CA 19-9 was 354. Although his signal for the EGFr inhibitor was very favorable in our analysis, I screened him for K-ras mutation. It seemed evident from his dose response curves and clear synergy between Irinotecan and the EGFR inhibitors that he would be K-ras wild type, but in this era of evidenced-based medicine one must be politically correct.

Indeed, he was K-ras wild type and we started treatment with Erbitux + Irinotecan. Other than the rash associated with the Erbitux, the tolerance was good. The bleeding stopped immediately, the CA plummeted with the first dose to 71 and the patient then returned every other week for therapy.

On February 11, 2011, three cycles later, we repeated the PET/CT. The phrase “marked interval regression” of measurable disease caught my eye. I also noted the normalization of his CA 19-9. The patient had gained weight and returned to normal activities. With the exception of a small and diminishing rash, he looks quite normal. In fact, with the rather modest dose of Irinotecan used in his schedule, he hasn’t even suffered any hair loss. What I find most interesting about this patient is that FOLFOX, the most widely used regimen in this setting, wasn’t anywhere on the radar screen. It wasn’t active, it wasn’t recommended and I feel confident it wouldn’t have worked. However popular FOLFOX may have come to be in patients like this, it doesn’t fit everyone.

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.

5 Responses to There is More to Gastrointestinal Cancer Management Than FOLFOX

  1. Sheri Torres says:

    My husband was diagnosed with duodenal adenocarcinoma on 31 December 2009. Stage 3b. He had a pancreas sparing whipple done and after recovery started dfox. He was unable to tolerate this treatment. He was given radiation to the area of anastomosis and location of lymphnodes. Xeloda was also given. He has had negative scans (CT and PET, EGD and camera endoscopies). However now has elected to start/try Folfox for 6months as an “insurance” policy. I am very nervous about this as his reaction to the D-Fox was beyond bad. I understand FolFox is different but duoodenal adenocarcinoma is not a well traveled road. And the fact that it is a almost 1.5 yrs. past diagnosis with negative scans/tumor markers makes it more difficult to wrap our minds around.

    I am grateful to have fond your blog and see there are other treatments being tried. This type of cancer is very confusing with it being so rare. We are looking for others who are dealing with this including oncology doctors to become more educated and share experiences. Thank you

    • I would anticipate that FOLFOX would be milder. D-FOX includes the drug Docetaxel, which in some patients can add toxicity. I share your concern that orphan diseases often have few resources. That is partly why we like to “customize” our therapies.

      When there is no right answer to a question there are often a large number of wrong answers.

      Our experience most recenlty with the Irinotecan based theapy has been gratifying but may not necessarily be right for your husband. Sight unseen, the FOLFOX seems reasonable and I hope will not be too difficult. If you wish to examine other options, you might ask for a k-ras mutation analysis. If negative (that is non-mutated) , this could be used if needed for future therapies with Erbitux or Vectibix.

      I wish you every success and would be happy to help if needed in the future.

  2. Pingback: What’s the Best Treatment for Metastatic Colorectal Cancer? « Dr. Robert A. Nagourney – Rational Therapeutics – Blog

  3. cheryl prevor says:

    Thank you Dr. Nagourney for sharing this excellent example of good diagnostic work. It never ceases to amaze me the extent of prescribing that occurs for drugs that are the “flavor of the month.” Patients deserve a good clinical assessment of whether a drug will work for them specifically.

    Sincerely,
    Cheryl Prevor, Psy.D.

  4. I agree. Chemo d’jour.

    Thanks for your comment.

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