Nearly a third of patients with pancreatic cancer can survive for five years on a combination of two drugs which are off-patent and have been used separately for years, an important charity-funded trial has shown.

Twenty years ago, all those diagnosed with cancer of the pancreas died within 12 months. But an international team of researchers, led from the University of Liverpool, revealed at the world’s biggest cancer drug conference that their trial has pushed the five-year survival rate from 16% to 29% of patients.

The combination of drugs – the chemotherapy drug gemcitabine, which is the standard treatment for the disease, plus a second chemotherapy drug called capecitabine – will now become the routine treatment for all pancreatic cancer patients.

Prof John Neoptolemos from Liverpool University, who led this and all the previous international trials in a series called ESPAC (European study group for pancreatic cancer) which began more than 20 years ago, said steady progress was being made against the disease.

“Twenty years ago there was little interest in operating on people with pancreas cancer because the mortality rate from surgery was very high – around 30-40%,” he said.
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The answer was to concentrate surgery in fewer regional specialist centres where surgeons became skilled because of the number of operations they performed. “It has helped to bring down the mortality rate in surgery from that horrendous figure of 30-40% to, in most places, 5-6% and in really good places like Liverpool, to 1-2%, from stopping the non-experts getting their hands on patients,” he said.

The ESPAC trials, which began publishing findings in 2004, showed that chemotherapy with gemcitabine brings five-year survival up to 15-17%, doubling the rate of survival with surgery alone. The latest research, presented at the American Society of Clinical Oncology meeting in Chicago, showed the two-drug combination nearly doubles the survival rate again to 29%.

It showed, said Neoptolemos, that chemotherapy does work in pancreatic cancer, even though most attention in cancer research is now focused on immunotherapy, and precision or targeted medicine.

But the trial would not have happened without funding from the charity Cancer Research UK (CRUK), because both drugs are old and off-patent, meaning they can be made by any generic drug manufacturer and are consequently cheap. Drug companies would not foot the bill for such a trial because the profits to be made are small.

“This is an academic-led presentation,” said Neoptolemos. “This shows the enormous value of CRUK. Without them, none of this would have happened. There is a lot of pressure [on doctors] to do drug company trials because you get £2,000 to £3,000 a patient. For something like this, you don’t get anything. It has been quite tough to do.”
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Another big bonus of the drug combination is that there are few side-effects, unlike many of the new biological treatments coming on to the market. The worst side effect of cancer treatments is often fatigue. “The last thing you want if you may be going to die of cancer is fatigue,” said Neoptolemos. “The rate of fatigue was quite low – for gemcitabine it is 5% and adding capecitabine it is 6%.”

The trial took place in hospitals in the UK, Germany, Sweden and France, where 732 patients who had surgery to remove their tumour were given either the one drug or the combination.

Pancreatic cancer is the fifth most common cause of cancer death in the UK and third in the United States. Every year about 9,400 Britons are diagnosed with pancreatic cancer and about 8,800 die from the disease. Globally there were 338,000 new cases in 2012 and 331,000 deaths.
Neoptolemos likens the progress against the disease to that in breast cancer, which used to kill half of the women diagnosed within five years but now has an 80% survival rate over 10 years in the UK. One of the next steps is to find biomarkers in the tumours that will tell doctors which drugs are likely to work best in the individual patient.

Prof Peter Johnson, CRUK’s chief clinician, was upbeat about the results. “Nearly 10,000 people are diagnosed with pancreatic cancer each year in the UK and it remains a very difficult disease to find and treat,” he said.

“Despite this we are making steady progress, through trials like this one, where the use of better chemotherapy after surgery was able to increase the number of people surviving the disease. We still have a long way to go, but Cancer Research UK is investing heavily into research to take on pancreatic cancer, and we are just starting to see the results.”