Vitamin D for Pancreatic Cancer – KLAS-TV

Vitamin D has been known for promoting strong bones, regulating blood pressure and even improving one’s mood. Could it be the key to fighting one of the most deadly cancers? 

U.S. researchers are testing the impact of adding vitamin D to the treatment regimen for some pancreatic cancer patients.

Seventy-six-year-old Daryl Fair retired from teaching American politics to travel and spend time with family. Earlier this year doctors treating him for pneumonia discovered something unexpected.

Fair told Ivanhoe, “It was a small tumor on the head of the pancreas.”

Doctors caught Daryl’s cancer very early, unusual for pancreatic cancer. Patients often have no early symptoms. Because he caught it early, Daryl qualified for a clinical trial, testing the impact of vitamin D on treatment.

Jeffrey Drebin, MD, PhD, Chairman of the Department of Surgery at Perelman School of Medicine of the University of Pennsylvania explained, “This is not vitamin D that you can get at the drug store.”

Researchers found that this potent vitamin D inactivates the body’s cells, called stromal cells that protect and feed pancreatic tumors.

“Vitamin D acts on these cells to make them quiescent” Dr. Drebin told Ivanhoe.

If the stromal cells aren’t working, researchers say chemotherapy drugs will reach the tumors and hopefully, wipe out the cancer. For now, patients are receiving vitamin D three times a week.

Peter O’Dwyer, MD, Professor of Medicine at Perelman School of Medicine of the University of Pennsylvania told Ivanhoe, “To get the high levels that we think we need within the tumor, we’re giving it as an IV in the initial trial of this.”

Fair explained, “I think studies like this are the things that are eventually going to make cancer readily curable.”

And bring hope to patients facing a tough battle.

Researchers say they would like to develop an oral form of the synthetic vitamin D, so patients in future trials could have the treatment at home. They say the results of this trial may also impact treatment for other stubborn tumors. Doctors Drebin and O’Dwyer are part of a team of collaborators being funded by “Stand-up To Cancer”.

Contributors to this news report include: Cyndy McGrath, Supervising Producer/Field Producer and Cortni Spearman, Assistant Producer.

BACKGROUND: According to the American Cancer Society, 48,960 people will be diagnosed with pancreatic cancer in the United States this year. Of those, 40,560 people will die from the disease. The pancreas is an organ that sits right behind the stomach. It is shaped somewhat like a fish with a wide head and a pointed tail. The pancreas is usually about 6 inches long and 2 inches wide in adults and has two different types of glands: exocrine and endocrine glands. The exocrine glands create pancreatic juice which helps you digest your food. The juice is released into the intestines, and without it, the food you eat would not be absorbed. More than 95 percent of the cells in the pancreas are in the exocrine glands. A smaller percentage of the cells in the pancreas are endocrine cells. The endocrine cells form small clusters known as islets which make hormones such as insulin and glucagon. These hormones are released directly into the blood to help regulate blood sugar. Pancreatic cancer can be found in exocrine cells and endocrine cells of the pancreas but both form different types of tumors.

ENDOCRINE AND EXOCRINE TUMORS: Exocrine tumors are the most common type of pancreas cancer. About 95 percent of cancers in the exocrine cells are known as adenocarcinomas. These cancers can begin in the ducts of the pancreas and can also develop from the cells that make up pancreatic enzymes. Endocrine tumors make up less than four percent of all pancreatic cancers. These cancers are usually known as pancreatic neuroendocrine tumors or NETs. NETs can be benign or malignant, and can look alike under a microscope. As a result, diagnosis may only become clear once the tumor has spread outside of the pancreas. Jeffrey Drebin, MD, Chairman of the Department of Surgery at the Perelman School of Medicine of the University of Pennsylvania told Ivanhoe “Unfortunately, most people with pancreas cancer are diagnosed when the disease has already spread and are not able to have a surgical cure.” (Source: http://www.cancer.org/cancer/pancreaticcancer/detailedguide/pancreatic-cancer-what-is-pancreatic-cancer)

NEW TECHNOLOGY: In a clinical trial where patients’ pancreatic tumors were removed and studied, Dr. Drebin and other researchers found that vitamin D makes the cancer cells inactive. Researchers particularly studied how stroma, which fuels the tumor and feeds it, creates a physical barrier stopping chemo from getting in. They then found that potent vitamin D doesn’t kill these cells but allows them to stop producing substances that feed the pancreas cancer. This is not vitamin D that you can buy at a drug store, but has been tested in animals and is now being tested in humans.

FOR MORE INFORMATION ON THIS REPORT, PLEASE CONTACT:

Steve Graff
215-349-5653
Stephen.graff@uphs.upenn.edu

If this story or any other Ivanhoe story has impacted your life or prompted you or someone you know to seek or change treatments, please let us know by contacting Marjorie Bekaert Thomas at mthomas@ivanhoe.com

Jeffrey Drebin, M.D., Ph.D. Chairman of the Department of Surgery at Perelman School of Medicine of the University of Pennsylvania explains how vitamin D infusions can help patients with pancreatic cancer.

Interview conducted by Ivanhoe Broadcast News in February 2015.

Can you explain pancreatic cancer and treatment options?

Dr. Drebin: Pancreatic cancer is a very tough cancer. It’s not that common as a cause of cancer. The incidence is only about twenty five percent of the incidences of breast cancer or lung cancer, but it’s a very common cause of cancer death. In fact, it’s predicted to be the second most common cause of cancer death within the next few years. The reason for that is unfortunately most people with pancreatic cancer are diagnosed when the disease has already spread and are not able to have a surgical cure. Radiation and chemotherapy can help keep the disease in check, but by themselves usually are not curative.

What is the standard treatment for somebody with this kind of cancer?

Dr. Drebin: With early stage disease, that would be disease that’s localized to the pancreas, which is not growing around major blood vessels in a way that makes it impossible to remove the tumor, it would be surgically removed and then generally followed by chemotherapy and radiation treatment. More than half of the patients have disease that has spread to the liver, lungs, and other places when the disease is diagnosed. Chemotherapy becomes really the only treatment and has improved in recent years. We’re now talking about one year and even two year survival for people with metastatic pancreas cancer, where we used to talk about weeks to months.

Tell me a little bit about the trial that Penn is involved in.

Dr. Drebin: This trial is an offshoot of the Stand up to Cancer, pancreas cancer dream team project, that I’ve been one of the co-leaders on. This is a project that involves physicians and scientists at multiple institutions around the country. The specific trial that we’re talking about today was based on a study that we did here at Penn in which our patient’s tumors were removed. We studied the DNA sequence of the tumor, we studied the metabolomics, the way it used its nutrition and we studied the stroma, the fibrous tissue that surrounds the cancer cells and helps feed the cancer cells. The cancer cells release substances that simulate the stroma and the stroma releases substances that stimulate the pancreas cancer, and also prevent the immune system from getting in and act as a physical barrier for chemotherapy getting in. When we sent our studies to collaborators at the Salk Institute in Ron Evans’ lab, he was able to demonstrate that the stellate cells, the stroma not the cancer cells, have a tremendous level of Vitamin D receptors. Vitamin D acts on these cells to make them quiescent. It doesn’t kill them, but it makes them stop proliferating, or stop producing substances that feed the pancreas cancer. In animal models, Ron’s lab was able to show that treating pancreas cancers in mice with chemotherapy was more effective if they also received a very potent Vitamin D analog. That background then led to the studies that we’re doing now, in which patients with respectable tumors, relatively early stage, are given chemotherapy plus high dose Vitamin D analog pre-operatively. Then, they have their tumor removed and receive additional cycles of chemotherapy plus the Vitamin D analog post-operatively.

In theory, what does the vitamin D essentially do in the animal models?

Dr. Drebin: We know that in our patient specimens that were removed and put in to tissue culture that Vitamin D shuts down the stroma cells. It makes them stop producing nutrients and substances called chemokines, which affect the immune system and affect the pancreas cancer and blood vessels. All of this acts to make the cancer grow better and resist the host efforts to fight the cancer. So, Vitamin D stops all of that. We know it stops it in our patient’s samples in tissue culture, we know it stops it in mouse cells in tissue culture and we know it stops it in mouse tumors growing in mice. Now, what we’re trying to do is bring that sort of bench science back to patients and ask will the Vitamin D analog do the same thing in patients with cancer to potentially make the chemotherapy work even better?

Can you explain Vitamin D analog?

Dr. Drebin: Sure. I want to stress this is not Vitamin D that you can get at the drugstore. Vitamin D is certainly a good thing if a physician recommends it, but it’s not something that I’m encouraging people to run out and buy bottles of and take. Vitamin D has an interesting property of inducing an enzyme that breaks it down. The more Vitamin D you take, the more that enzyme is induced, and the more it’s broken down. At some point, just buying Vitamin D over the counter will not be effective and can have side effects. The analog we use is very potent and resistant to degradation, so it acts on the same receptor that we know is in the stroma cells in the cancer, but it doesn’t get broken down by that enzyme that Vitamin D induces. Therefore, it has effects far more potent than would be possible with Vitamin D taken by mouth.

Who would be the ideal candidate for a treatment like this?

Dr. Drebin: A patient who wants to pursue a promising but not yet proven addition to treatment using the vitamin D analogue. We think we can say that the vitamin D analougue is doing in the patient specimens what Vitamin D does in the tissue culture and in the mouse experiments. We know it’s hitting its target and doing what we expect it to do. To prove that it makes chemotherapy work better will require a bigger study, but the ideal patient for this study would be someone with an early stage pancreas cancer, either stage one or stage two, but is potentially amenable to surgery. We also look for someone who is able to tolerate chemotherapy and who is able to have three Vitamin D infusions per week. Sometimes, when we have patients who come to Penn from two or three hours away, it’s not reasonable to expect them to drive in three times a week for the infusion. We certainly have a fair number of patients who are getting more traditional therapies that don’t involve three times a week Vitamin D infusion.

Is there a risk to patients taking this additional Vitamin D infusion?

Dr. Drebin: It could potentially have a variety of side effects. We have not seen side effects in most of our patients other than the normal effects of chemotherapy.

What’s the next step?

Dr. Drebin: After we complete this trial, which I hope will be done in the next few months, we will conduct a larger Phase II trial in which we ask is it really helping us to cure more patients. We’ll probably need between one and two hundred patients. We would probably collaborate with several other high-volume pancreas cancer surgery centers like Penn to try to accrue patients quickly so we can approve or disprove the idea that this is really a next step forward in treatment.

Is there a bottom line? Is this encouraging news?

Dr. Drebin: I’m very cautious because in pancreas cancer research, we have sometimes over-promised and under-delivered. I would be delighted if this is a next step to curing more patients. Certainly, based on the animal data and the tissue culture data using our patients’ specimens, we have reasons to be hopeful. The other thing that’s worth recognizing is that the Standup to Cancer Foundation funded us to do this research initially in two thousand nine. The studies didn’t really get going until two thousand ten, two thousand eleven. In that time, we accrued multiple collaborators and over a hundred patients in the study of the stroma cells in tissue culture as well as the other correlative studies on the cancer specimens, did the mouse experiments to prove that it worked, brought it back and opened a human clinical trial and will have completed that clinical trial in the next few months. So, to go from an initial clinical trial back to the laboratory, back to another clinical trial in about a five year time swing may seem like a long time for patients with cancer. But, it’s a cycling process that will let us add to knowledge and make improvements faster. One of the great things about the Stand up to Cancer mechanism is that it’s allowed us to do this quickly.

This particular trial is for early stage and non-recurrent?

Dr. Drebin: Not recurrent and non-metastatic. It would be just for patients whose disease has not spread. There will be trials opening up in advanced disease in the near future, probably both here and at several other of our collaborative sites. But, those trials are probably weeks to maybe a month or two away. All of us in the pancreas cancer research and treatment community recognize that this is a tough disease and that people can’t wait. We try to get these things open to people as quickly as we can.

Is there anything you would like to add?

Dr. Drebin: Two things first: do not to go out and buy Vitamin D. Second, pancreas cancer is a tough cancer and you want to be treated at a center with experience and take advantage of clinical trials if possible. This is not a disease where I think any of us rest on our laurels and say we do great with it because it is such a tough cancer. The more people we have in clinical trials trying to improve outcomes, the more chances we’re going to have to really move the bar forward in improving cures for this disease.

This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.

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