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  • Dr. Robert A. Nagourney, MD

IS STAGE 4 METASTATIC PANCREATIC CANCER CURABLE?

Few cancers strike greater fear into patients than pancreatic cancer. With over 60,000 new cases per year and 48,000 deaths, this disease is among the most lethal of all human malignancies.


Unfortunately, pancreas cancer does not have any early signs or symptoms. Most often, people complain of weight loss. Some patients develop jaundice and others low back pain. But by the time most patients are diagnosed, the disease is no longer curable.


Over the years, oncologists have developed a number of chemotherapy combinations, the most widely of which used is FOLFIRINOX and Abraxane plus gemcitabine. They carry response rates of 31% and 23% respectively with median survivals of less than one year.


Recently, investigators have extended the concept of “kitchen-sink” therapy by giving everyone-everything-all the time. This group combined gemcitabine, Abraxane, and platinum with all 3 of these drugs administered at full dose for consecutive weeks


As one of the people who developed cisplatin plus gemcitabine, I am extremely familiar with this drug doublet, both from a standpoint of activity and more importantly toxicity. I have also studied the Taxanes (one of which is Abraxane) and have examined the interaction between all of these drugs in almost every imaginable way.


Remembering that drugs can act together in ways that are more than additive, the term for this supra-additivity is “synergy”. We have shown that Abraxane is not synergistic with Gemcitabine and that cisplatin is not synergistic with Abraxane but that Gemcitabine is very synergistic with cisplatin.


When physicians decide to put drugs together “because they can”, instead of because they “work better together”, patients receive too much of the wrong drug and not enough of the right drug, all at the cost of extraordinary toxicity.

Strikingly, this triple-drug combination provided a high response rate but at the price of a 12% mortality. Mortality!


There are very few treatments in modern oncology that would be hailed as a success if 12% of the patients treated died from toxicity, yet this new 3 drug combination is being touted as a breakthrough. More disturbing is the fact that the three-year survival for this lethally toxic regimen was a measly 4%. Thus 3 times as many people die from the treatment as live 3 years all predicated on the principle that more is better.


I return now to the title of this blog – Is metastatic stage 4 pancreatic cancer curable? The answer is yes, but it is not a trivial undertaking.


First, you must intervene first-line and not wait until patients have failed FOLFIRINOX or Abraxane. Second, each patient’s cancer must be examined at the time of diagnosis to evaluate the drugs and combinations that are most effective and synergistic.


Biopsies of the liver or aspiration of fluid to obtain tissue can be the difference between life and death when choosing among chemotherapy combinations.


One patient who we cured of Stage IV pancreatic cancer had a liver biopsy right at the time of first diagnosis that identified a novel 3 drug combination proving both effective and synergistic. He achieved an immediate and complete remission now 11 years long.


Not every patient will have such a good outcome. These results reflect the interplay between the individual patient and the drugs selected. However, curable patients should be cured and incurable patients should not be subjected to unnecessary toxicity or death.


Researchers around the world are slowly beginning to recognize the importance of human tumor primary culture analyses like the EVA/PCD analyses that we conduct. Some of the most outspoken former naysayers are now scrambling to recreate our work. The problem is that there are many slip-ups in the process.


Many of the newcomers have simply turned their 2-dimensional “cell-line” culture systems into 3-dimensional “cell-line” culture systems. As these researchers have failed to maintain the natural architecture of the native-state tumors with vascular, inflammatory, and stromal components their efforts are virtually certain to fail.


Only fresh explants removed directly from the patient can possibly recreate the conditions of the patient’s body to provide accurate predictions of response.


We have conducted over 380 pancreatic cancer studies using our EVA/PCD method. The results have been critical for the good outcomes of many patients, even curative in some.


If you or someone you know has been diagnosed with pancreatic cancer, you should immediately seek culture analysis to select your treatment. Do not allow physicians to simply ramp up the doses arbitrarily at your expense.

The blind administration of multiple toxic drugs at full doses to provide an investigator with their coveted “publishable” observations could easily cost you your life.


Cancer treatment is a delicate balance between efficacy and toxicity. Patients must use their own tissue to make these decisions. In pancreatic cancer, it is a matter of life and death.

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