Chemotherapy is the use of cytotoxic drugs to destroy cancer cells, because cancer cells are dividing quickly they are particularly susceptible to chemotherapy (as are bone marrow and gastrointestinal cells).
When is chemotherapy used for pancreatic cancer?
Chemotherapy can be used in various ways in the treatment of pancreatic cancer:
It may be given after surgery to try to eradicate any cancer cells that may have spread elsewhere in the body (‘micro-metastases’). This is called adjuvant chemotherapy and studies have shown that it can significantly improve survival.
If doctors cannot remove the cancer by surgery, or if it has been only partially removed or the cancer has spread to other parts of the body, chemotherapy can be used to try to shrink the tumour, relieve symptoms and prolong life. Whether or not chemotherapy is recommended depends on several factors, the main one being general fitness to cope with chemotherapy and its possible side effects.
It may also be given before surgery, with the aim of improving the successful removal of cancer. This is called pre-operative, or 'neoadjuvant' chemotherapy: it is not yet standard care for pancreatic cancer (the ESPAC-5F trial and the PRICKLE trial are looking into its effectiveness see Cancer Research UK for more details).
Dr Pippa Corrie is a Consultant and Associate Lecturer in Medical Oncology at the Cambridge University Hospitals NHS Foundation Trust (Addenbrooke's Hospital).
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.
What is the standard chemotherapy treatment?
Standard chemotherapy treatment for pancreatic cancer is intravenous gemcitabine given in combination with other chemotherapy drugs for those able to cope. Some oncologists combine it with capecitabine (a tablet form of fluorouracil). The ESPAC-4 clinical trial is looking at whether or not it is better to give people capecitabine as well as gemcitabine after surgery (see ‘Clinical trials’). Some researchers have recommended this combination as first line treatment for people whose pancreatic cancer is inoperable. More recently, a chemotherapy combination called FOLFIRINOX (leucovorin, 5-flourouracil, irinotecan and oxaliplatin), was compared to gemcitabine in patients with advanced pancreatic cancer and was shown to be more effective. However, the side effects are significant, so this regimen is only likely to be an option for patients who are feeling well despite their cancer and are prepared to accept a higher risk of treatment related complications. Gemcitabine is usually given alone for those who are less fit.
Dr Pippa Corrie is a Consultant and Associate Lecturer in Medical Oncology at the Cambridge University Hospitals NHS Foundation Trust (Addenbrooke's Hospital).
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.
Most people we interviewed had the standard treatment of intravenous gemcitabine with or without tablets of capecitabine. Gemcitabine was given once a week for three weeks followed by a week’s rest from treatment (this is called a 'cycle' of treatment). Those who were taking capecitabine took the tablets every day for the first three weeks of each cycle. Having no treatment in the fourth week allows the body and blood cells time to recover before the next treatment. An allergic reaction after Maureen’s first treatment delayed her second treatment. Treatment typically lasts for six cycles with regular check-ups but some people had less. For instance, Adrian’s condition deteriorated, so chemotherapy was abandoned after only one cycle.
Peter is a retired bank manager. He is married and has two adult children. Ethnic background/nationality' White British.
So for the next month or so there was more scans and bits and pieces, and then they arranged chemotherapy commencing on September 22nd, in three cycles, on the day 1, 8, 15 basis. I.e. day 1 is the first treatment, and a week later day 8, 2nd treatment, third treatment day 15, fourth week day at rest and then start again.
Do you know what the chemotherapy was called?
And it wasn’t part of a clinical trial?
No. No. Where was I? Oh they said, “After the three cycles we shall scan you to see how you’re getting on. And we have to tell you that should it not be working we shall have to withdraw the treatment and we’re sorry but you’ll be on your own”. Good news wasn’t it? But anyway we carried on. I missed a fair few of the treatments, usually the 2nd one for some reason, which I know not what.
And, anyway, come December they did a scan and told me, well they told the surgery, I’ve got the letter somewhere under a pile of papers, they told me that not only had the tumour stabilised, it had decreased.
Oh that was good.
In the order of 70%.
And so the treatment, the chemotherapy will be continued.
However, some people had other drugs. For example, Alison had gemcitabine with cisplatin, and David (Interview 09) had fluorouracil. Peter (Interview 36), who had a neuroendocrine tumour, which is rare, had three chemotherapy drugs' streptozocin, fluorouracil and adriamycin. His doctor had to import the streptozocin from the United States because it is not licensed in the UK. It can be used only in a few people whose specialists think that it may help them. This special arrangement is called named-patient prescribing. Peter received daily chemotherapy as a hospital in-patient for a week each month for three months - the rest of the time he was at home.
Peter is a journalist. He is married and has two children. Ethnic background/nationality' White British.
I remember when the chemotherapy arrived from America, it was treated by the nurses a bit as though it were kind of semtex, you know, sort of a banned substance. It came in sort of yellow bags, and it was handled with care. Well so it seemed to me anyway.
So for each treatment you had to get it from America?
I think it, well yes, I think it came, I’m not quite sure how, I never asked quite, or maybe I did but I forget. I don’t know what form it came from America. But it came from America yes. I think they must have had some kind of license to use it. I don’t think it was like banned in the sense that it was, it just wasn’t, yes it wasn’t licenced for use exactly, and apparently there are quite a lot of chemotherapies like that, and chemotherapy’s been around since the first world war and some of the early ones were pretty unpleasant and not very effective and they gradually get replaced by better ones that are more, that are more precise and have fewer side effects. But that leaves behind possibly, and it certainly seemed to me, a number of drugs which have worked in the past, even if they are unpleasant which people didn’t use anymore. Anyway this was one of those. And I agreed to have this pumped into me for a few months to see what happened...
I was treated as an in-patient for a week. And I remember it was a cycle. It was a very strange experience to me. Obviously I’d never had chemotherapy before. I’ve since discovered this is, there are a lot, many of these cycles. I was in hospital for a week having the stuff intravenously, and being watched over quite carefully while it was being put in… I had a week in hospital. And then the rest of the time I was at home....
And that was for three months?
And that was for three months after which they said they would have a look and see if anything had happened. And I had, I mean my impression, certainly from people, at the time and since, was that the people who were doing this did not really think that anything would happen.
Nab-paclitaxel (Abraxane) is also sometimes given for advanced pancreatic cancer in combination with gemcitabine. “Nab-paclitaxel is not widely available on the NHS at the moment for pancreatic cancer. The National Institute of Health and Care Excellence (NICE) have not made a final decision about whether to approve it. But the Scottish Medicines Consortium (SMC) have decided to recommend its use on the NHS in Scotland. In England, doctors may be able to fund it through the Cancer Drugs Fund.” Cancer Research UK June 2014.
Recent research studies have also shown that pancreatic cancer can be split into four unique types (known as stable, locally rearranged, scattered and unstable* and it was shown that some of the people with the ‘unstable’ type of pancreatic cancer benefited from being given platinum-based chemotherapy drugs (such as cisplatin) typically used for testicular or ovarian cancer but not normally given for pancreatic cancer.** Further research into this is planned.
How is chemotherapy given?
Most chemotherapy drugs are given intravenously (injected into a vein in the arm or back of the hand) usually via a cannula (a tiny flexible tube that is inserted into a vein which can be used to take blood or give medicines) which stays in until the treatment is over. Some chemotherapies are given as tablets. Gemcitabine is given intravenously. Some people dreaded having intravenous chemotherapy because the nurses sometimes found it difficult to put the needle or cannula into a vein. One man said that his veins ‘went into hiding’ when he went for his chemotherapy and it took nurses three or four attempts before they found a vein. Carol also said that she ‘hated those needles’.
If it is very hard to find a vein a ‘central line’ or ‘portacath’ can be used to give the chemotherapy and other treatments, as well as to take blood samples. These are tubes that go into one of the major blood vessels, and which can remain in place for however many months the person is receiving treatment. The end of a ‘central line’ may hang out onto the chest wall and is visible. The external part of the line is secured under a plastic dressing and a small clip is attached to the skin by a couple of stitches. Alison had her chemotherapy via a type of central line called a Groshong line (see ‘Radiotherapy and chemoradiotherapy’). Some people have a portacath, which is not usually visible. A portacath is a small chamber that sits under the skin at the end of the ‘central line’. When a person needs treatment, the nurse puts a needle into the chamber, through the skin, and gives an injection or attaches a drip. Rory, a woman we interviewed, recommended having a portacath.
Rory is a retired teacher. She is married and has three adult children. Ethnic background/nationality' White British.
And how many hours do you sit there with the infusion?
Usually it’s half an hour, half an hour. And I’ve got a portacath.
Can you explain to me what a portacath is?
[Laughs] well, I’m not medically trained so I might not be telling you exactly right. But once again I wasn’t told about this, I found out from another patient who said, “Oh what you want is a portacath”, because my veins are very deep seated and I was getting myself into a terrible state wondering if the nurse would be able to find my vein and oh it was dreadful. And I had some very unpleasant experiences, you know, while they were trying to find a vein. And then the vein would collapse. So having talked to somebody else who was on a different cancer treatment to me she said, “Oh, what you want is a portacath”. She said, “Don’t let them put one of these others in”, she said, “which is all exposed”. She said, “Just have one of those,” she said, “and you can even swim with it.” So that’s what I’ve had. And what they do is they insert a little valve underneath your skin and this leads directly into your vein so I can have the intravenous chemotherapy and they just if you like, plug me in really. You can’t use it for a CT scan because apparently the people in the CT department aren’t specialised to use this portacath then, I still have to have it, the vein found conventionally. But it means, it’s saved my veins …
... and it means that when I do have to have blood taken obviously weekly, excuse me, my veins are in a fairly good nick considering I’ve had so much chemo, chemotherapy, excuse me.
Is the valve covered with anything? Or is it just …
No, just my skin. No, nothing.
Nothing After I …
How do they get to it?
Well they, if you’ve, it’s like a little lump and that leads directly into the vein and they access it with a needle.
Oh I see, through that little bit of skin.
That’s right, yes.
The people we interviewed usually had a choice about whether or not they should start chemotherapy. Some people said that their doctors had made all the treatment decisions and that that was fine, but others wanted to be more involved in decision making.
Those who had been offered chemotherapy to shrink the tumour to make surgery possible (neoadjuvant chemotherapy) were keen to have it because it seemed to be the only option. People who had already had surgery usually had chemotherapy without questioning the decision because their doctors usually recommended it, but a few people, like Ann, were very reluctant to start treatment (see below). Tony said he had been frightened because he didn’t know what chemotherapy involved. The people who had inoperable cancer, or who had had a recurrence, often had chemotherapy to alleviate symptoms, or as part of a clinical trial. Some felt that they lacked enough information to make an informed decision (see ‘Finding information’). A few decided to discontinue treatment or decided not to have any treatment at all because their doctor had told them that the side effects might outweigh any benefits.
Ann is married with 3 children. She was a GP for over 35 years til her retirement when she developed pancreatic cancer, co-founder of the charity that runs healthtalk.org inspired by her own experience of breast cancer, and Medical Director of the Oxford University Health Experiences Research Group. Ethnic background/Nationality' White British.
So you got back from the summer…
… and you felt pretty well. Optimistic?
Yes, optimistic and well, because once you stop feeling ill actually, I mean, I certainly wasn’t thinking about, well I managed not to think about the prognosis really, which I knew wasn’t terribly good but I managed just to put that on hold and not think about it, until I had to go and see the consultant and talk about what I was going to do, chemotherapy or not. And I certainly, I think, before I went away in the summer I was saying, “I’m definitely not doing it.” I felt quite pressurised about doing it, having at least some of it, at least trying it and the statistics I’d been given, I had a 60% chance of recurrence within two years, which I was quite shocked at how high it was. And that if I had the gemcitabine, which is one of the chemotherapies that they use that has been shown to be more effective than the 5-Fluorouracil, which they used to give, which if you take that for six months weekly then you, the likelihood of recurrence is down to about, is brought down by 20%, so that would be 40%. But of course, within that you don’t know who’s actually going to benefit. And whereas with the operation I knew I had to have it. If I didn’t have it I would obstruct, get jaundice and be very ill and die. With this it’s very different, it’s thinking, “Well it might help and it might not but while I’m having it I might be very ill. So that was a really, really difficult decision, and I kept not wanting to think about it, in fact tried not to think about it.
When you say you felt pressurised, do you mean by yourself or by other people?
Both really. I felt pressurised by myself in that I felt if I get a recurrence and haven’t done it, people will say, “Well it serves you right.” And they may not actually say it but they probably would think it, “Well that was a silly thing to do.” So I felt slightly pressurised by myself. I felt more pressurised that my family particularly wanted me to at least try it. And my friends, that I should at least try it because a lot of people said, this particular chemotherapy isn’t so terrible, it doesn’t make people so, so ill.
Age at interview:
Age at diagnosis:
Dorothy is a housewife. She has three children. Ethnic background/nationality' White British.
When he suggested that you didn’t have any more treatment, like chemotherapy, was that an easy decision for you to make, or did you think about it for a while or look for information or?
No, I didn’t look for any information at all. I haven’t got a computer or anything so I can’t get on the net. I didn’t look for any information because I thought right, if that’s what they say, I’m, in my mind I thought I may have had this for a while, it may go on for a long while still just in the same position, therefore, just, just go along with it. Just go along with it. I didn’t think oh yes I must have, I ought to have some sort of treatment to get this better, no, because I wasn’t and I am still not in any pain from it.
A scan is often undertaken before chemotherapy treatment starts to act as a baseline measure so doctors can evaluate the effects of treatment by comparing it with later scans. Before each intravenous chemotherapy infusion people had blood tests to check that their blood (red and white cells and platelets) was healthy enough to withstand the drugs, and some had also had their blood pressure and body weight checked.
Alison is married and has 2 children. She is a PhD student. Ethnic background/Nationality' White British.
And was that, were the hospital surroundings and the treatment all right?
Yes, yes. It was a private hospital, and it was a nice clinic. There were oncology specialist nurses there, as well as nurses who dealt specifically with chemotherapy. And my consultant had his clinic on a, on a certain day in the morning. You’d go in and you’d have, you’d be weighed and have your blood pressure done, and then you’d have your bloods checked to see that everything was, was all right. Mainly your neutrophil count they’re, they’re looking at, to, to ensure that the chemotherapy wasn’t actually zapping you of your resources as it were. And if that was all fine, they also checked the cancer marker on a monthly basis as well, but if that was fine, then they’d go ahead with the chemotherapy. And it took I’d say from start to finish, I’d usually go in for about 9 o’clock and I’d be out by about 4.
A long day.
So it was a long day. But I had my own private room, so I could take my laptop in, I could read. I could do my own thing.
Most people had their chemotherapy in an NHS outpatient clinic, but a few people had private treatment and had their own room, even as an outpatient.
Michael is a retired wine merchant. He is married with one adult child. Ethnic background' White, half Polish half British.
And I think the other thing that when I started the chemotherapy, the clinic I was in was absolutely fantastic in the, I can only call it sort of love and affection and professionalism they gave one. And when you went down there you were the sort of celebrity there. Everything was done to make your visit there as comfortable as possible and they were very sensitive and they were always enquiring, asking how you are and what they could do to try and help you. And you had alternative treatments there. You could have reflexology, reiki or aromatherapy, and the other thing for women, which I thought was, and even men if you wanted it, there was a woman there who gave talks on image. So, you know, how to dress if you had, for women, if they had hair loss, they told them the sort of hairstyle, sort of make up to use, and I think this was a number of, well, lots of women had a session there and that really helped them I think enormously so that so they could still feel attractive during this treatment. It wasn’t so relevant to men because I don’t think we think too much like that, but it… Then there was someone who, a specialist in nutrition, a specialist in homeopathy and then a psychiatrist who could give you advice if you had emotional ups and downs. So there was not only the medical team but there was this tremendously helpful support team around you, and again, the doctors who looked after me were all internationally known and again were absolutely brilliant in the way they, the positive attitude they took with one and encouraged one and helped one get through the troubles.
People having chemotherapy usually spend several hours in the clinic, including seeing a nurse or doctor, having tests and waiting for the drugs to be prepared before having the treatment itself. Most people described the atmosphere in the clinic as ‘pleasant’ and said the nurses were excellent and tried to make them feel relaxed. Some mentioned comfortable arm chairs, books to read, DVDs to watch, and access to refreshments. Chatting to other people who were also having treatment was a pleasure for some and could be a source of support.
William is married and has 2 children. He is a lorry driver (not working due to ill health). Ethnic background/Nationality' White British.
What happens on that Wednesday?
You go, I start the cycle by having a blood test on the Monday. And then on the Wednesday they look at the blood test and then so long as everything is okay they’ll give me the chemo. And they put my hands in hot water to make the veins come up and then they put the cannula in, in one of the veins which they’re happy to put in. And they flush it through with a solution while they wait for the pharmacist to mix my chemo. Because the hospital I’m at doesn’t buy its chemo in, it actually mixes it themselves. And that can be a two-hour wait, sometimes three hours waiting for the, the chemo to come down from the pharmacy. And all the time you’ve got a slow drip just going through your cannula. And then they come with the chemo. And that chemo bag takes twenty minutes. And after twenty minutes they just flush through the tube and then you’re free to go. Take the cannula out, put a plaster on the, the spot, and then you come home. So the whole procedure can take three, four, sometimes five hours.
And the staff in that department?
Rushing around, overworked, very pleasant. And the cancer charity comes round making people cups of tea and if you’re there at lunchtime they bring you a sandwich. And there’s reading material. There’s a DVD you can borrow. So it is made as pleasant as it can be. But it’s all right. You can’t complain. You start to know people. So, you know, the Wednesday team, you see the same people, so you strike up a relationship with them.
However, others had felt uncomfortable sharing their treatment sessions with large numbers of other people, and didn’t want to chat to other people. Phil was shocked when he found himself in a room with 40 other people, and said that it was too impersonal having lots of different nurses looking after him within the same treatment session. Simon and his wife found the clinic rather depressing.
Simon is a teacher. He is a widower and has two children. Ethnic background/nationality' White British.
Can you describe what happened during a sort of typical day of having her chemotherapy?
In the early days at the, at the NHS hospital you know, you walk into the waiting room full of you know sick people. A big waiting room, it was quite a busy department really. And we always felt very uncomfortable there and, quite sort of, I don’t know, what’s the word, sort of self conscious in a way as well because Karen was you know, for someone with cancer was very young. She was only 39, so we were younger than most people there. And she also looked well. I mean even, even months into her treatment, after months of chemotherapy she looked as well as anyone else. I mean she was just so physically healthy and fit. So we’d sort of go in there, these sort of, you know we felt relatively young, healthy looking people.
And I always felt slightly self conscious, but also just depressed by the atmosphere in there because it’s just, it’s just not nice. I mean you know people are friendly, and we, but we didn’t really want to, Karen never saw herself as a patient. So she was never going to be one of these who would go into the waiting room and get to know people, because you see the same faces every week. But she was never going to do that. She, we would sort of stay on the outside and just read a magazine and try and take our minds off it.
And then going to the, you know the chemo room, which was very odd the first time I, we went in there because, it just looks like another, well I suppose it looks like a treatment room, but just with armchairs. And there were just people casually sitting there, reading magazines, with a drip in their hand. And again, being ignorant as to really what goes on, what chemo was, I always thought you’d be in a room with all sorts of equipment and, so it seemed all very low key.
And you know she would sit down, they’d go through all the paperwork, checking her name and double checking and all that sort of rigmarole. And get her hooked up. She never liked the needle going in, it always hurt a lot. And I think she was just tense you know. And then it was a case of just sit there with the machine next to you pumping away, beeping away, and I would sort of sit with her and we’d talk and try and take her mind off it. There was a lovely woman who used to come round and give us biscuits and you know get drinks.
Do you know what her chemotherapy was called?
Yes, she had gemcitabine and another one that I can’t remember now.
Yes. Gemcap yes, that was it. So she had both.
So she had that for a few weeks first of all?
Yes. Well this was, this was on the trial so it was, I think it was twelve weeks of chemo. But it was every, they were four week cycles so I think it was three weeks on and then one week off.
People who didn’t like the idea of having toxic drugs put into their body tried to look on the positive side – that it was intended to help them. Carol referred to her treatment as her ‘best friend’. After their treatment some people continued to associate certain smells with chemotherapy, such as a particular perfume worn by a nurse.
Michael is a retired wine merchant. He is married with one adult child. Ethnic background' White, half Polish half British.
I just felt I was poisoning myself, and in fact, I much preferred going into the clinic, I went to a private clinic, and having the gemcitabine drip, and all that, all the sort of treatment, well, it was basically the gemcitabine drip. What I had was I would go two weeks - it was a three week cycle with one week off - and I’d go in every week to have the gemcitabine drip and then I’d come home and I’d have the capecitabine tablets and a load of these other tablets to counter any side effects. But I was taking a sort of massive amount of tablets and it really, I did I did feel that I was poisoning myself but one had to try and put it in a more positive frame of mind that in fact one might be but at least it was doing one’s body some good and getting rid of the cancer.
People often experienced side effects of treatment (see ‘Side effects of chemotherapy’). More information about chemotherapy and about ‘central lines’ and portacaths can be found at Macmillan Cancer Support.
*International Cancer Genome Consortium (ICGC) – a global project which aims to read, analyse and understand the genetic make-up of different cancers.
** Waddell, N., et al. (2015). Whole genomes redefine the mutational landscape of pancreatic cancer Nature, 518 (7540), 495-501 DOI: 10.1038/nature14169