Dr Pippa Corrie - Interview 44

Brief Outline:

Dr Pippa Corrie explains that there are different types of pancreatic cancer and that sometimes chemotherapy is useful. She also talks about the standard chemotherapy for pancreatic cancer and about some of the clinical trials that are taking place in the UK.

Background:

Dr Pippa Corrie is a Consultant and Associate Lecturer in Medical Oncology at the Cambridge University Hospitals NHS Foundation Trust (Addenbrooke's Hospital).

A consultant oncologist explains that taking part in a clinical trial may give a patient an opportunity to access 'state of the art' treatment.

We were talking about treatment trials. What are the advantages of taking part in a treatment trial?

 

The most important advantage I think is for patients to be allowed to access state of the art treatment. So when treatments are relatively limited then clearly if you can access, or optimise your, give yourself the best chances of an improved quality and quantity of life, then it may well be by accessing treatment within a clinical trial.

 

The other issues that are slightly more subtle are that as part of being involved in a trial protocol you usually have very close access to a clinical team, the doctors and research nurses, which sometimes is beneficial. I think it gives people a certain sense of safety.

 

A consultant oncologist explains why some patients may not have the opportunity to take part in clinical trials.

Who is eligible for a treatment trial?

 

We’d like to say most patients. Because the treatment options are relatively limited, it’s great to be able to give patients access to newer treatments, state of the art treatments within the context of clinical trials. But there are certain limitations; every protocol will have certain criteria that patients need to meet. And some of these are about patient’s safety, particularly if treatments are being tested in the early stages where safety issues may not be entirely understood. 

 

Also, some of these trials, particularly when in the early stages, are only open in a small number of centres, and so it may not be locally available to you, although specialist teams will know what’s available in their region and elsewhere and you are always allowed, and you’re within your rights to be referred elsewhere. But then you have to think again about the practical issues of travelling and so on.

 

A consultant explains that there are other trials taking place including trials involving PET...

Do you want to talk about any other clinical trials that are taking place in the UK at the moment? Are there any others?

 

So there are a number of different treatments around being tested, in different stages of development. We have an interest in imaging of pancreatic cancer, which is notoriously difficult, and there’s a new imaging technique called PET CT, which may help to identify tumours at an early stage, and response to treatment early. And so some centres in the UK are involved in a trial where they are receiving conventional chemotherapy, but also having their tumours assessed by PET scanning, which is not the norm, because normally one would use CT scanning.

 

Are there any other clinical trials? 

 

Yes. Yes so they’re, so you will find that across the country there are a variety of different new drugs being tested, either separate to, or in addition to chemotherapy. Again as I was mentioning, as we learn more about the molecular biology of cancer, then new molecularly targeted treatments are being developed and tested, either on their own, or in association with conventional chemotherapy. So you might hear things like notch inhibitor, or hedgehog inhibitor, or an angiogenesis inhibitor, these are all different classes of agents that are currently being tested for pancreatic cancer.

 

A consultant explains that people may have little time to come to terms with death and dying, but that the hospital team and the community teams are there to help them.

When people reach near the end of their lives, what might they expect?

 

I think one of the hardest things is because pancreatic cancer can grow and spread very quickly it is a hard time for them to take in what’s happening to them. And sometimes they may not even get the opportunity to have any form of anti-cancer treatment.

 

So needing to come to terms with death and dying can be one of the hardest things. Everybody deals with that in different ways, and both the hospital team and the community teams will be there to try and help them to come to terms. Sometimes issues like needing to put affairs in order, particularly for example for younger people with young children, needing to really very quickly try and make provision for a family, can be very hard at a time when also people are developing a lot of symptoms. So it is a very complex and very difficult time. And so again both hospital and community services are geared to try and support people in every way that they can depending upon the individual’s circumstance.

 

A consultant explains that people with advanced pancreatic cancer are likely to get many symptoms and various specialists will contribute to their care

What about if the cancer comes back? Could you summarise what palliative care, the care that might be offered to help the symptoms?

 

So, when patients develop recurrence of pancreatic cancer, and they usually are referred to oncology doctors, we offer in the first instance chemotherapy, to try and improve survival, but we’re very aware that patients may have symptoms associated with that cancer, so part of our job is actually to concentrate on symptom control. 

 

Now chemotherapy, gemcitabine has been shown in itself to be very good at helping to dampen down symptomatology associated with advanced disease. But there are lots of other things that could be done, and patients can run into problems with pain, with jaundice, and with ascites. They tend to lose a lot of weight, and they tend to get very low mood, and all these kind of things mean that quite often we need more help than just oncology doctors. So quite often we will involve people like palliative care doctors and our nutritionists, and other experts, pain [relief] doctors to try and help deal with the symptoms.

 

A consultant explains that pain can be treated by specialist teams and that symptoms such as jaundice and ascites (excess fluid) can be treated too.

What would be the most worrying symptoms quite near the end of life? I imagine pain is something that you have to control.

 

I think patients fear pain the most. We are constantly asked questions about that. Some cancers can be more problematic with pain control, and pancreatic cancer can be because the position of the pancreas is right in front of a large nerve plexus. And infiltration of that nerve plexus by the cancer can cause pain. But again, we have very specialist teams, both acute pain [relief] teams involving anaesthetists in the hospitals, and palliative care teams in the community, with all sorts of different ways of trying to deal with that particular problem.

 

Are there any other symptoms that you should mention?

 

Patients can run into problems with jaundice, if they develop obstruction to the bile duct. And ascites, so accumulation of fluid in the abdomen can also be problematic.

 

Would you sometimes drain that?

 

Yes, so again, drainage of ascites is a routine procedure from our perspective and we are now trying to find ways of being able to do that more in the community to avoid patients having to come into hospital.

 

A consultant explains what cancer is and why it may develop in any part of the body.

So cells in the body are continually growing and dying, and they have to be replenished normally. And so the cells normally grow and divide under a very controlled process, but sometimes that controlled process goes wrong and uncontrolled growth leads to cancer. And this can happen in any organ of the body, such as the pancreas, and generate what we know as pancreatic cancer.

A consultant talks about a common type of pancreatic cancer, pancreatic adenocarcinoma, and a less common type, neuroendocrine pancreatic cancer

And are there different types of pancreatic cancer?

 

Yes, there are two common types and the normal pancreas cells do two things. They’re involved in digestion, generating enzymes that help to break up our food. Or they’re also involved in hormone production, in particular insulin.

 

Now each of those different functions are generated by different cells of the pancreas, and if those cells go wrong they create different types of pancreatic cancer. The common one, we know as pancreatic adenocarcinoma is the one associated with the cells associated with our digestive system. And that’s a particularly aggressive type of cancer.

 

Another one which is less common we call pancreatic neuroendocrine cancer, and this tumour arises from cells that seem to have an hormonal function, sometimes generating the insulin, so you can form things like insulinomas, but sometimes actually arising from other hormonal cells, both in the pancreas and in other parts of the body, whose function we don’t fully understand. But these tumours we call neuroendocrine carcinomas and they tend to have a less aggressive pattern of behaviour. And it’s important to know which type you have because you treat them very differently. 

A consultant explains why gemcitabine and capecitabine (a tablet form of fluorouracil) are often used in combination.

And what is the standard chemotherapy?

 

So the standard chemotherapy in advanced disease is a drug called gemcitabine. It’s a well tolerated drug, and it’s given in the outpatient setting. And it’s a very acceptable treatment for most people to be able to live alongside and continue a reasonable quality of life.

 

And that drug is also being used in the earlier stage, in what we call the adjuvant setting, although the treatment that’s had the most evaluation is a drug called 5-fluorouracil, and that drug’s been around a long time, but more recently evaluated in the context of colorectal, sorry pancreatic cancer, and shown to be beneficial.

 

So some patients may be offered a 5-fluorouracil based chemotherapy regime, and others may be offered gemcitabine. But on the whole the benefits look pretty much the same.

 

If patients say that they’re having gemcitabine and capecitabine, would they be on a clinical trial then?

 

No. Because the first work, the first treatments developed in pancreatic cancer have been 5-fluorouracil and gemcitabine. And so one could argue that if you put those two drugs together might you get better outcomes. Now more recently 5-fluorouracil, which is given intravenously, has been largely replaced by an oral formulation called capecitabine. And trials have been done with this combination, mainly at the moment in advanced disease, and an important trial called the gemcap trial was performed in the UK and compared gemcap to gemcitabine, and although it showed that there were better response rates, there were, more tumours appeared to shrink, the overall survival benefits were the same. So there is some controversy really as to whether or not the standard of care is gemcitabine or gemcap, and some centres will choose one and some centres will choose the other. That combination is now being tested in the adjuvant setting.

 

A consultant explains when chemotherapy is used for pancreatic cancer.

Could you just sum up when chemotherapy is recommended and why in different situations?

 

So if we concentrate on pancreatic adenocarcinoma, the more common form of cancer, we use chemotherapy in two main situations. Firstly after surgery, we know that patients still have a very high risk of recurrence from that disease, and so the overall survival of patients with pancreatic adenocarcinoma, even if they’ve undergone potentially curative surgery, is not good. And we’ve used both, in this country and worldwide, we’ve evaluated the role of what we call adjuvant chemotherapy, chemotherapy after surgery, to try and improve the outcome, and improve survival rates. And studies have shown that in this context using chemotherapy does improve survival chances. So we now have standard adjuvant chemotherapy for pancreatic adenocarcinoma. 

 

But those benefits are still limited, and we’re always trying to improve upon that, so sometimes patients are offered alternative treatments in that context, usually within clinical trials. 

 

In advanced disease, because again outlook is not great, and survival durations are relatively limited, again we are trying to kill off tumour cells that are spreading throughout the body and again chemotherapy is used here. The role again is quite limited, at the moment the treatment that is offered as standard improves survival in the order of weeks and months, and not years in general. So again we’re trying to improve on that treatment all the time by looking and seeing whether we can use different forms of chemotherapy, or now, what are called molecularly driven treatments. Because we’re learning more about these, the cellular mechanisms that control cancer and now clever people in pharmaceutical companies are actually discovering new drugs that can be targeted against the specific processes that we think are controlling the cancer process, and sometimes using those either instead of or in combination with chemotherapy.