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.
Gregory D. Pawelski