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  #11  
Old 03-11-2016, 12:31 AM
gdpawel gdpawel is offline
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Default Functional Profiling for Stage IV Pancreatic Cancer

Robert A. Nagourney, M.D.

The battle against Stage IV pancreatic cancer is every bit as challenging as a hard fought military campaign. Not unlike our comrades in arms, we must fight from “foxhole” to “foxhole” to gain ground against this entrenched enemy. With a response rate of 20% and 5-year survival of 1%, pancreatic cancer is an adversary that is unwilling to take prisoners.

Once, when I approached a colleague from a major pancreatic cancer program about a clinical protocol for pancreatic cancer patients with ascites he described them as “dead men walking”. This came painfully to mind when I recently met a 50-year-old gentleman with newly diagnosed, extremely advanced, pancreatic carcinoma.

The patient arrived in my office on January 6th, 2016 with the all-too-common complaints of weight loss, low back pain and the recent onset of diabetes. A CT scan identified a mass in the pancreas, peritoneal studding, ascites and a large lesion in the liver. Needle biopsy confirmed adenocarcinoma.

When I met the patient he was pale, gaunt and ill appearing. He moved slowly, like a man 30 years his senior, as he climbed uncomfortably onto my exam table. I could feel fluid in the abdomen and immediately referred him to ultrasound where I removed 550 cc of ascites fluid by paracentesis for EVA/PCD functional profile.

As we awaited the assay results, I examined the blood tumor markers. His CEA was 91.1 (normal 0-2.5). More striking was his CA19-9 at 22,454 (normal 0-30), fully 750 times the upper limit of normal. The EVA/PCD assay on day 7 returned highly favorable results and I selected a novel 3 drug combination from among the tested options.

Recognizing the gravity of the situation we placed a Port-A-Cath and started chemotherapy treatment January 18th just 12 days after I had first seen the patient.

As luck would have it, on the first day of therapy, the patient presented with an extremely swollen left leg, and was found to have a DVT (blood clot). This common complication of pancreatic cancer known as Trousseau’s sign usually indicates a very dismal prognosis. Undeterred, we started anticoagulation and continued treatment. A repeat CA19-9 was obtained. The results were astonishing. The patient’s tumor marker had risen from 22,454 to 275,796; now over 9000 times the upper limit of normal!

After just one cycle of therapy, barely two weeks in, the patient returned looking demonstrably improved. His color was good and he had stopped accumulating ascites fluid. The left leg remained swollen but he felt better. The striking findings were the tumor markers. His CEA had fallen from 98.7 to 27.8 and his CA19-9 from 275,796 to 104,359. Encouraged by these results we continued on to cycle 2 after which I met with the patient and his wife to begin cycle 3.

Less than two months since our first meeting the patient was a new man. The color had returned to his cheeks. He was gaining weight. The ascites had completely resolved. He was hungry and felt well, very well.

Jokingly, I made a wager with the patient and his wife, betting that his tumor marker would be less than 25,000 after cycle 3. The patient said 100,000 and his wife, 75,000. We each bet $1.00. After receiving the laboratory results, I called the patient and said that I had good news and bad news. The good news was that the CA 19-9 was 12,090 and the CEA 5.7. The bad news was that they both owed me $1.00.

Pancreatic cancer is not untreatable. It may not even be incurable.

It simply requires the right treatment the first time. We believe that pancreatic cancer may be an extraordinary opportunity to prove the merit of functional profiling like the EVA/PCD assay and we look forward to assisting every new pancreatic cancer patient as we continue to pursue the best treatment for every patient.

Unfortunately, pancreatic cancers are often advanced when first diagnosed and the only option left is chemotherapy. Despite years of study, there are no curative therapies for metastatic pancreatic cancer. Nonetheless, some patients have dramatic and durable benefit from chemotherapy.

We find that advanced metastatic pancreatic patients fall into several broad categories:

1. The truly drug sensitive patients who will respond to numerous treatments and can benefit from the least toxic drug combinations

2. A small minority of patients who are sensitive to "targeted agents" like Erlotinib (Tarceva).

3. A large group of patients have distinct sensitivity to one of the three standard drug regimens used in this disease: Platinum-based (GemOx, Cisplatin & Gemcitabine), Taxane-based (GTX, Abraxane/Gemcitabine), or Irinotecan-based (FOLFIRINOX, FOLFIRI).

4. A final group of patients are resistant to standard chemotherapeutics and should be considered for experimental therapies as early as possible.

Today, patients are selected for treatment based on physician experience, ease of administration or the cost of the chemotherapy combinations. Think what would happen if each patient received the therapy that was best suited to their unique tumor makeup.

This is why functional profiling of your tumor to determine which drug or drug combination will most likely kill YOUR specific cancer is so important.
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  #12  
Old 06-02-2016, 06:26 PM
gdpawel gdpawel is offline
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Default Hospice Nurse Confronts Stage IV Pancreatic Cancer: Her Own

Robert A. Nagourney, M.D.

With 53,000 new pancreatic cancers diagnosed each year and 41,000 deaths, pancreatic cancer is among the most lethal of human malignancies. The 5-year survival of 7.7% drops to 2.6% for patients with advanced disease and most patients present with advanced disease.

Not surprisingly, oncology specialists engaged in palliative and hospice care know pancreatic cancer very well. Thus, there was a cruel irony when one of my long time colleagues, an accomplished hospice nurse, contacted me in February to inform me that she had been diagnosed with inoperable, metastatic cancer of the pancreas.

The work-up identified the abdominal disease but it was the PET-CT scan that raised concern when a lymph node showed up in the neck. The thoracic surgeon who conducted the biopsy found that the lymph node was completely replaced by adenocarcinoma. This enabled us to perform our 3D functional profile.

The results proved extremely interesting as the patient was resistant to many drugs and combinations used in this disease. Gemcitabine, Cisplatin plus Gemcitabine and the widely used FOLFIRINOX were inactive. Despite this, Abraxane plus Gemcitabine showed good activity that was further enhanced by the addition of 5FU to the cancer cells in culture, revealing clear evidence of synergy. Quite clearly the best regimen would be Abraxane plus Gemcitabine plus 5-FU, a somewhat novel twist on a drug combination known as GTX.

As I analyzed the laboratory results I was struck by several findings, among them, the utter inactivity of Cisplatin. This drug, alone or in combination is the backbone of many pancreatic cancer treatments, but had absolutely no activity here. The second was good activity for 5-FU. This drug was the original (and for many decades the only) treatment for this disease. Finally I was impressed by the substantial contribution that 5-FU made to the doublet of Abraxane and Gemcitabine. One additional finding was the favorable profile for the diabetes drug Metformin. With this in hand we started Gemcitabine /Abraxane/ Capecitabine combined with low dose oral Metformin.

The patient tolerated the treatment well with moderate hand-foot syndrome from the Capecitabine. Within a week the nagging, right-sided abdominal pain had disappeared and the patient's tumor marker fell by 50%. After an additional cycle, the PET/CT revealed a very good response. The patient continues on therapy with a new lease on life.

There is a quote from the bible, Luke 4:23, “Physician heal thyself.” It is interpreted several ways. One interpretation is that physicians must focus upon their own needs before attending to the needs of others. While I have the utmost respect for our excellent hospice nurses, this is one stage IV pancreatic cancer patient for whom I hope hospice care will never be needed.
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  #13  
Old 09-14-2017, 02:32 PM
gdpawel gdpawel is offline
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Default Choosing Therapy For Stage 4 Pancreatic Cancer: What Are The Criteria?

Robert A. Nagourney, M.D.
Medical and Laboratory Oncologist

Pancreatic cancer afflicts 53,000 patients each year in the U.S. and has overtaken breast cancer as the third leading cause of cancer death in the United States.

While newer chemotherapy combinations have had some impact, the gains have generally been modest and obtained at the cost of significant toxicity.

How Do Oncologists Choose Metastatic Pancreatic Cancer Treatments?

A recent analysis examined patterns of chemotherapy use in the United States and came to some interesting conclusions regarding how medical oncologists choose treatments for their patients.

The study analyzed 4,011 patients with metastatic pancreatic carcinoma (stage 4 pancreatic cancer) treated at both academic centers and private practices and compared patterns of drug use from January 2005 to December 2015.

Analyses included the choice of treatment regimen and the frequency with which second and third line therapies were administered.

In 2017, available therapies for advanced pancreatic cancer include single agent Gemcitabine, Gemcitabine plus Capecitabine, Gemcitabine plus Erlotinib (Tarceva®), Oxaliplatin plus Gemcitabine and the widely used FOLFIRINOX and Gemcitabine plus nab-Paclitaxel regimens.

Results of the Survey

The findings are of interest.

First, the use of single agent Gemcitabine declined rapidly over the last ten years from over 70% to only 16%.

Since 2010, FOLFIRINOX use has risen to 29% and Gemcitabine plus nab-Paclitaxel to 38% of patients. Gemcitabine plus Erlotinib (Tarceva®) and Gemcitabine plus Oxaliplatin have each remained low, in the range of 10%.

What was most striking was the analysis of factors associated with physician choice of drug regimen. While one might hope that objective measures and scientific data drive therapy selection, the findings painted a rather different picture.

It appears that the use of FOLFIRINOX is predicted by younger age, male gender and geographic location with patients who reside in the Western United States having a higher likelihood of receiving this drug regimen in the first-line.

The independent predictors for the choice of Gemcitabine plus nab-Paclitaxel are the receipt of care in a community-based practice and treatment in a center with a lower volume of Stage 4 pancreatic cancer patients.

Durations of therapy were similar for FOLFIRINOX and Gemcitabine plus nab-Paclitaxel and longer than single agent Gemcitabine but these differences were not very large. Second and third line therapy has increased demonstrably over the ten-year period, with patients receiving care at academic institutions having the highest likelihood of receiving third line chemotherapy.

Some Points to Consider

The analysis raises a number of interesting points that warrant further consideration.

The first is that these treatment regimens do not have equal response rates. Indeed, FOLFIRINOX has an almost 35% higher objective response rate over nab-Paclitaxel plus Gemcitabine (31% vs. 23%).

The second is that these combinations are not of equivalent toxicity or expense to administer.

The third and most disturbing is the fact that no objective measure is applied to make critical, life and death decisions regarding what combination to use in this seriously ill population.

Were I a cancer patient, I would certainly hope the choice of my treatment was predicated upon more than my age, gender and geographic location.

It is the last point that is of most concern.

Is There a Better Way to Choose Treatments?

Laboratory models such as the EVA-PCD ASSAY can select amongst treatment options.

It is not difficult to imagine that for any given patient, one class of drugs may be more active than another. Clearly nab-Paclitaxel plus Gemcitabine work differently from FOLFIRINOX.

Are we to imagine that all patients have equivalent treatment response expectations? And that all patients will have equivalent toxicities?

Is it too much to expect medical oncologists to make the effort to identify the right treatment for each patient, in a disease that kills 41,000 of the 53,000 patients diagnosed each year?

It seems it is time for patients with Stage 4 pancreatic cancer to demand more of their physicians.
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