TeloVac Vaccine Trial Holds Hope For Diabetics With Pancreatic Cancer

More than 1,000 patients with advanced pancreatic cancer have joined the final stage trial at 53 hospitals in Britain

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LIVING with diabetes means being diligent about listening to your body for any signs or symptoms that something isn’t quite right. Most people with diabetes know to watch out for issues with their circulation, kidneys, and even gums; but how many realize they should be on the alert for cancer, specifically pancreatic cancer?

Pancreatic cancer is the eighth major form of cancer-related death worldwide, causing 227 000 deaths annually. And Type 2 diabetes is widely considered to be associated with pancreatic cancer. But whether this represents a causal or consequential association is unclear.

Researchers have found that about 80 percent of people who have pancreatic cancer also have glucose intolerance (blood sugar levels that are high, but not yet at diabetic levels) or diabetes.

Another study found that people diagnosed with diabetes after age 50 are eight times more likely to develop pancreatic cancer compared with the general population.

Indeed, pancreatic cancer has the worst survival rate of all common cancers ‒ just three in 100 patients survive the disease for five years or more.

New-Onset Diabetes May Help Guide Pancreatic Cancer Screening

It is for this reason that the Phase-3 (final stage) trial in the UK on the GV1001 vaccine (TeloVac) to treat pancreatic cancer is being followed with great interest around the world. The vaccine is being developed by GemVax AS, a subsidiary of Pharmexa A/S.

Vaccines are usually associated with preventing infections, but this is part of a new approach to try to stimulate the immune system to fight cancer. The trial involves regular doses of the GV1001 vaccine (TeloVac) together with chemotherapy and compares this with chemotherapy alone.

One of the best documented therapeutic cancer vaccines currently in development, GV1001 is a 16-amino acid peptide vaccine that comprises T cell epitopes from human telomerase, an enzyme which is over-produced by cancer cells.

The vaccine ensures robust activation of both CD4+ (memory) as well as CD8+ (cytotoxic) T-cells. The aim is to stimulate the immune system to recognize the telomerase which sits on the surface of the cancer cells and to target the tumor.

Professor John Neoptolemos from Royal Liverpool University Hospital, who is helping to co-ordinate the trial, said: "The problem is tumors are clever and are able to turn the immune cells into traitors which help to guard the tumor. The vaccine takes away the masking effect of the tumor."

Cancer Research UK's chief clinician Professor Peter Johnson said: "One of big problems with cancer treatment is you are almost always left with a few malignant cells and it is from those few cells that the cancer can regrow. If you can program the immune system to recognize those cells and get rid of them altogether or keep them in check then you can effectively stop the cancer from growing back lifelong."

Controlling Diabetes May Reduce Cancer Risk and Death

Doctors usually treat advanced pancreatic cancer with gemcitabine(Gemzar) and capecitabine (Xeloda) chemotherapy. But there is evidence suggesting that using a type of treatment called immunotherapy as well as chemotherapy may give better results. Immunotherapy is a type of biological therapy.

The TeloVac trial is to see whether giving the GV1001 vaccine as well as chemotherapy will improve treatment for pancreatic cancer.

Immune system cells search for and kill abnormal cells. But they don’t always recognize cancer cells as being abnormal. The GV1001 vaccine works by teaching immune cells to recognize certain proteins (antigens) made by pancreatic cancer cells. The immune cells can then find the pancreatic cancer cells and kill them.

Doctors want to find out how well the GV1001 vaccine works when it is used with chemotherapy as well. The aims of this trial are to see:

• If adding GV1001 to gemcitabine with capecitabine chemotherapy helps pancreatic cancer treatment to be more successful

• What the side effects are when GV1001 is added to gemcitabine with capecitabine chemotherapy treatment

• How well GV1001 helps the body’s immune system to attack pancreatic cancer cells

The Phase-3 TeloVac trial should produce results in just over a year which will show whether the vaccine has a positive effect. Cancer Research UK is keen to stress that the vaccine is not a cure, but if it works, might prolong life.

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Pancreatic Cancer Risk and Diabetes: What Can You Do?
If you have diabetes, there are ways to reduce your risk of pancreatic cancer and increase your chances of catching it earlier if it does occur:

• Be aware of pancreatic cancer risk factors. Some risk factors for pancreatic cancer cannot be changed, such as being over age 60, being African-American, being male, and having a family history of pancreatic, colon, or ovarian cancer. Other pancreatic cancer risk factors, however, can be reduced or eliminated, including being overweight and smoking.

• Ask for tests. Going with the hypothesis that pancreatic cancer may cause diabetes, it would be reasonable for people newly diagnosed with diabetes to ask their doctor if there are any tests they should have to rule out pancreatic cancer. Because the non-specific early symptoms of pancreatic cancer — pain, jaundice, and weight loss — can be hard to detect or easily confused with other diseases, pancreatic cancer diagnosis may be difficult and often is not made until the cancer has spread.

• Eat a healthy diet. Once it is determined that pancreatic cancer is not behind the diabetes diagnosis, it is important for people with diabetes to keep their blood sugar levels under control by eating well-balanced meals in the right portion size.

• Stay active. Exercise is another important aspect to work into your daily schedule, especially if you are overweight. Losing the extra pounds can be doubly beneficial by helping keep the diabetes under control and reducing the overall risk for developing pancreatic cancer.

Finally, simply be aware of your body and how you feel. If you experience abdominal pain, sudden weight loss, or any other significant changes, be sure to call your doctor.

Source: CancerHelp UK

New-Onset Diabetes May Help Guide Pancreatic Cancer Screening

A new diagnosis of diabetes may help identify older adults who will develop pancreatic cancerwhile there is still time for screening and early detection, researchers reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

In an observational study of more than 20,000 older adults with pancreatic cancer, 10 antecedent diagnoses were found to be significantly associated with the cancer diagnosis.

Of these, a diagnosis of new-onset diabetes preceded the cancer diagnosis by the greatest amount of time – more than 2 years, on average – or potentially enough time to catch the cancer early with targeted screening. A diagnosis of abdominal pain was second, at 1.5 years.

Late diagnosis is a major contributor to the generally "dismal" survival of pancreatic cancer, lead investigator Dr. Elizaveta Ragulin-Coyne said in an interview.

"Colonoscopy screening works great, mammography works great. But those cancers are really a lot more common, so it makes sense to screen the whole population," she commented.

By contrast, pancreatic cancer is relatively uncommon, so population-based screening with current tests would generate many false positives. At present, only individuals from families having hereditary pancreatic cancers associated with certain mutations are screened.

The goal of the study was therefore to identify "the factors that can precede the diagnosis of pancreatic cancer, that sort of can act as red flags to identify that population at risk," she explained. "So we are trying to identify the risk-rich population of individuals who can benefit from potential future screening."

The investigators analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database for the years 1991-2005 and the linked Medicare database for the years 1991-2007 to identify older adults with a diagnosis of pancreatic cancer and diagnoses preceding the cancer.

They evaluated 30 possible antecedent diagnoses for their association with the pancreatic cancer diagnosis, and narrowed it down to 10 that were significantly associated (P less than .05) in a stepwise logistic regression analysis: acute pancreatitis, chronic pancreatitis, cyst-pseudocyst, other pancreatic disease, bile duct obstruction, diabetes, weight loss, jaundice, abdominal pain, and hepatomegaly.

The 22,493 study patients were 77 years old on average; 55% were women and 86% were white, according to results reported in a poster session at the meeting.

The 10 antecedent diagnoses ranged in prevalence in this population from a low of 4% for hepatomegaly to a high of 76% for abdominal pain. A diagnosis of diabetes was seen in 45%.

In most cases, the median time between the antecedent diagnosis and the pancreatic cancer diagnosis was less than 3 months. The exceptions were abdominal pain, diagnosed a median of 18 months before the cancer, and diabetes, diagnosed a median of 28 months before the cancer.

The latter intervals are long enough to provide a window of opportunity for intervention, according to Dr. Ragulin-Coyne, a surgical resident and research fellow at the University of Massachusetts Medical Center in Worcester.

"It doesn’t make sense if you have preceding diagnoses within a month before, it doesn’t really make a difference," she explained. "But if it’s over 6 months or over a year, it is actually clinically significant because you can hypothesize that those people are potentially at an early stage and could have more interventions that give you a possibility of cure."

The average number of antecedent diagnoses decreased with increasing stage of pancreatic cancer at diagnosis, from 3.91 among patients with stage 0 disease to 2.04 among patients with stage IV disease.

This finding initially seemed counterintuitive, Dr. Ragulin-Coyne said. But perhaps patients having more advanced cancer at diagnosis have had less contact with the health care system in general, and therefore have fewer diagnoses on record.

In a logistic regression model among just the patients with an antecedent diabetes diagnosis, the odds of the gap between that diagnosis and the pancreatic cancer diagnosis being greater than 24 months were higher for nonwhite versus white patients; for patients aged 75-84 years or aged 85 years or older, compared with those aged 65-74 years; and for patients in the Midwest versus the Northeast.

The reason pancreatic cancer is diagnosed earlier in some patients and later in others is not yet clear, but it is likely multifactorial, according to Dr. Ragulin-Coyne.

"We can make guesses, whether it is socioeconomic or cultural or there is something else in play." For example, some patients may "tell the doctor about all their symptoms and get worked up early and get their doctors concerned more," she said. "But if they never come to the physician or they never mention what’s going on, they get diagnosed late."

In any case, identifying the reasons will be critical to moving all patients into the early diagnosis group. "I think that will ultimately be the best thing if, when they come, we can offer them treatments and cure and options, versus just saying, unfortunately, it’s too late," she commented.

The investigators have obtained the SEER data for all similar older adults without a pancreatic cancer diagnosis, and using a matched analysis, plan to develop and test a prediction nomogram using the information from their study. "Stay tuned for that," she advised.

"Screening for pancreatic cancer will be a great future tool," Dr. Ragulin-Coyne concluded, while also cautioning that there is still much work to be done before some type of population-based screening becomes a reality.

By: SUSAN LONDON, Internal Medicine News Digital Network