Dr Andrew Davies – Royal Surrey County Hospital, Guildford, UK
Dr Jason Boland – Wolfson Centre for Palliative Care Research, Hull, UK
Dr Didier Mayeur – Hopital Mignot, Paris, France
Dr Ante Koller – Institut für Pflegewissenschaft, Vienna, Austria
AD: Hello, my name is Dr Andrew Davies, I’m a consultant in palliative medicine from the UK and I’d like to welcome you to this expert advisory discussion about breakthrough cancer pain. It’s great to have you all here. What I’d like to do to start off with is talk about the whole concept of breakthrough cancer pain and whether people really understand what it is. So maybe we can start by what you understand it is and what you think your colleagues understand from the term.
JB: Breakthrough cancer pain is an exacerbation of the pain over the baseline. So we know that patients with cancer often experience pain and if that’s well controlled with regular analgesics they still might get exacerbations of the pain over and above that and that’s commonly known as breakthrough cancer pain.
AD: And do you think that concept is well recognised within oncology?
DM: I’m not so sure; in France I’m not so sure at all because we have data showing that breakthrough pain and pain is still not well controlled. Because recent research from the National Institute of Cancer showed that nearly half of the patients are not well controlled.
AK: I see this in my data too, that we have more of a problem with uncontrolled baseline pain and the concept of breakthrough pain is not yet reached.
AD: So we have a problem in managing cancer pain but in those patients that do have well-controlled background pain and then exhibit these exacerbations that Dr Boland has talked about, do you think how he has described it is universally recognised as being breakthrough pain? Do people use the term? Obviously there are different translations but is that a well-known concept in your countries?
DM: It’s not a well-known concept in France, not yet. We are working for that. All the societies - pain societies, medical oncology societies – are working for that but it’s a long time to have a recognition of this concept and it’s a long time for the students to learn that.
AK: From my point of view the oncology nurses know about breakthrough pain and the concept. They understand the difference between short-acting and long-acting.
AD: And for those patients who do have breakthrough pain what sort of impact does it have on their day-to-day life.
JB: Massive. Massive.
DM: Yes, that’s a good word, yes, I think so.
AD: And perhaps you could give me some examples of a patient maybe that you’ve seen and how breakthrough pain would interfere with the activities of daily living.
DM: Pancreatic cancer, for example. Pancreatic cancer patients have frequently breakthrough pain; patients with bone metastasis also. It’s a real great .... , if I can say that, for breakthrough pain.
AD: And traditionally breakthrough pain has been broken down into two types, the spontaneous pain where the pain comes on with no obvious exacerbating factors and then incident pain. You alluded to people with bone metastasis, so is incident pain a big issue in the patients that you see?
AK: It is and it’s the difference between the foreseeable and unforeseeable pain. You have to put this into the education because you handle it differently, don’t you? And patients don’t understand that, they wouldn’t think of it on their own.
AD: So, in my practice I see a number of patients with breakthrough pain, particularly patients with bone metastases, for instance, who have real problems mobilising because the pain becomes so severe when they try to walk. It can be a very challenging condition, problem, to manage.
AK: And they don’t think of taking the pain killer in advance before they are doing this foreseeable thing they want to do. It impacts their life, their daily life, very much.
DM: They don’t think or they are afraid to take them also.
AK: Both. Both.
AD: So we have issues in terms of managing cancer pain in general, a bit of a lack of understanding about breakthrough pain and the concept of breakthrough pain. But we know that it exists, it’s probably very common, I know the data varies about the prevalence, and it has a big impact on the quality of life. So when we have patients with breakthrough pain or you have patients with breakthrough pain, what are the sorts of strategies that you might consider in terms of trying to improve that breakthrough pain?
JB: I think the first thing, because in the UK the term breakthrough cancer pain is well-known, but I think the issue is around assessment, not only assessment of the background pain but to properly assess the breakthrough cancer pain. Without that proper assessment of how it’s affecting the patient, what makes it come on, the type of breakthrough cancer pain, and patients might have more than one type of breakthrough cancer pain and actually each episode might be slightly different. So there’s not only inter-individual variability but intra-individual variability. So the first step has to be a very thorough assessment of the pain, the breakthrough cancer pain, the timing of onset, how long it lasts for, what people have tried and the effect of that.
DM: I do agree. There is one more difficulty, I think, it’s to make the difference between the in-patient and the out-patient because the in-patient moves less and so on and it’s more difficult to assess, really, for the out-patients.
AD: So, to paraphrase what you’ve been saying, it’s a very heterogeneous condition. Everybody has a different type of breakthrough pain, they need to be properly assessed and the treatment needs to be individualised for that one patient. As you said, Dr Boland, some patients will have multiple types of pain, just like they have multiple types of background pain. So what are the strategies that can help these patients?
JB: Once the assessment has been made and it has found out much more detail about the breakthrough cancer pain I tend to try and divide it into is there anything reversible, so is there anything that can be done to reverse the pain? Then we’ve got other strategies like non-pharmacological and then I’d come on to pharmacological.
DM: In my department we also have multidisciplinary teams, with specialists of pain and the mobile palliative care team also and the medical oncologists, just to have a look with what about cementoplasty, for example, radiotherapy, chemo-targeted therapy, pain killers, of course, and so on. This is, to my mind, very important to talk together to choose a good way of treating these patients.
AD: So it’s very similar to background pain, then, there are lots of strategies that may be useful in individual patients and often people need more than one intervention. Going beyond trying to treat the underlying cause and lifestyle adaptations, for a lot of patients we need to give them some sort of pharmacological intervention to help with the pain, usually that’s some sort of an opioid. I just wondered what was the current practice in the areas that you work in in terms of the use of opioids to treat breakthrough pain?
JB: Most commonly oral opioids are used for any type of pain exacerbation above and beyond the slow-release. Most people with cancer pain will probably be on slow-release opioids, maybe some other drugs as well. Then still, despite the evidence probably showing that oral opioids aren’t even absorbed by the time the breakthrough pain episode has already finished, I still think they’re most commonly used.
AD: And would you say that’s the same sort of situation?
DM: I think so. We have also to identify what is this breakthrough pain – is it nociceptive, mixed, neuropathic, it’s not the same, and how long does it last? Because if you have to manage breakthrough pain that lasts less than five minutes you know that even transmucosal fentanyl will not be efficient in such a short time so it’s useless to give them. This is perhaps forgotten by some practitioners.
JB: This comes back to what you said about potentially if someone knows they’re going to do something that brings on the pain as part of that assessment using something beforehand, understanding the pharmacokinetics and giving that at a good time beforehand so the dose is in their system.
AD: You talked about the transmucosal opioids, they have different names – they are rapid-onset opioids, fast-acting opioids and whatever – and they’re invariably based around fentanyl. I wondered about your thoughts about using those drugs – should they be used? Are there particular groups that might benefit from them? Are there particular groups that you wouldn’t want to use them? I wondered what your sort of experience might be.
AK: From my point of view the patient needs to know what they’re doing and if they don’t understand what they’re doing the short-acting opioids will not be in good hands, especially the rapid-onset ones. If you take your time and give them the good education and take the caregivers in as well then you could start and work with the patients to really be active in their lives. You talk about the foreseeable pain and the unforeseeable pain and you talk what do you do then and what do you do then. The less complex the regimen is, the more the chance, the higher the chances are, that the patients will use it to their best advantage.
AD: So it’s not just about prescribing a particular drug, you’ve got to do all the education and provide all the support for it to be really effective.
AK: We call it patient-related barriers and there is a lot of research around that. We know that a lot of patients don’t really know how to take their medication. There are some practical barriers, some cognitive barriers, the most frequent one would be fear of addiction, for example, and it’s very deeply rooted in society. Some physicians and some nurses do have the same fear as well.
AD: So if we just stick to that point for the moment, maybe, do you think there are some patients who would benefit from opioids more generally and specifically for breakthrough pain where they’re not being given those because of fears of healthcare professionals or maybe other constraints in the health service?
AK: I think that’s happening a lot, yes.
AD: And what about in terms of your practice of using these drugs?
DM: There are some populations where we do not want to use these kinds of drugs, especially patients who had in the past addiction to opioids. Sometimes we do it, we do use them with a lot of time of education but when they stopped the addiction the patient doesn’t want to go back and they don’t want to take back this kind of drugs. That’s a real problem also.
AD: But in terms of their effectiveness are there particular groups of patients that you’ve found these rapid-onset opioids to be particularly useful in?
JB: Drawing on your point, if their pain lasts probably between 10-30 minutes, so in that barrier so by the time the rapid-acting fentanyl products start to work, i.e. around 10-15 minutes depending on the route of administration and before oral opioids will kick in, so in those people oral immediate release opioids are useless, probably, because they’re not even absorbed probably within that timeframe and these products come into their own.
AD: You mentioned about maybe the prophylactic use of medication, I wondered if anybody had any experience about telling patients to take the medication before they were going to do something that would bring on the pain?
AK: I keep telling them and they think it’s a good idea, most of them, because it makes them get in control of their active life again and it gives them some more chance to get up from the sofa and go for a walk, for example, or do some cleaning or something. It’s funny things people like to do when they can again.
AD: And in terms of adverse effects, you mentioned the potential risk of misuse of the drugs and that’s true of all opioids, but in terms of other effects, adverse effects, are these drugs generally well tolerated?
DM: Very well tolerated.
JB: They’re well tolerated because there is some data suggests fentanyl might be better tolerated than some other opioids or maybe has less side effects. But because we individually titrate these drugs we titrate them to effect, monitoring for side effects, rather than sometimes what happens with, say, oral immediate release opioids – they might be given at a higher dose than the patients need, although they should be individually titrated as well, that’s maybe less common in clinical practice.
AD: So, if I’m right, we all feel that these drugs can be very useful, very effective, generally well tolerated in a specific group of patients. What’s really important is the assessment to make sure that it’s the right treatment for that patient and that patient’s pain. I just wanted to move on a bit. You’ve talked about your individual practices and experiences and just about guidelines and whether there are any guidelines that you particularly follow, either just general cancer pain guidelines or specifically some breakthrough pain guidelines?
DM: In France there are guidelines which are being written at this time so I hope it will help the use of these kinds of drugs in the future because medical oncologists don’t have time or are not always interested by these kinds of topics, they prefer to read about immunotherapy or the last targeted therapy. It’s a real problem, so such guidelines written in French will help. Some medical oncologists don’t read the English guidelines in this part of their practice.
AD: So it’s important to have local guidelines with local experts and obviously written in the local language. What about in Germany?
AK: Well nurses wouldn’t read English guidelines as well so we need them in German here. I see a lot of good prescribed drugs and then the patients wouldn’t know how to take them because it leaves them some room for interpretation. You have the baseline and you have the breakthrough pain medication and they switch both ways. If they are not well educated some patients will never understand the difference and then you have to get in the caregivers or whatever. It’s the same with in-patients and out-patients, we see it all the time. The most frequent mistake that is made is that they take the medication with the meals, which is from time point not the correct time.
AD: That’s a very interesting point, we all acknowledge that that happens and it’s very interesting because they’ve recently been reviewing the international guidelines and there is nothing about this education and support of the patients, even though we all know that that’s a fundamental issue. Do you think guidelines are generally followed and are useful? You mentioned the oncologists, do you think they need some guidelines because they’re not going to read the original literature? Do you think they have an important role within clinical practice and certainly in your practice?
JB: I hope so. In the English language there are several guidelines and I tend to follow the regional guidelines and there are, indeed, national guidelines in the UK. I probably don’t think they’re followed as well as they could be. There are some key points in the guidelines you’ve outlined about the assessment and how we might manage it but that reassessment is so important. Whatever has been done for the breakthrough cancer pain, is it working? Do the background opioids or other drugs need titrating? Or if they’re used pre-emptively then you certainly wouldn’t want to add them into the background drugs. So sometimes the guidelines are followed, maybe they’re a bit misinterpreted and not used correctly because often I see in clinical practice the background pain not being properly managed, the breakthrough cancer pain being even poorer managed and then when people are on opioids often the opioids can be escalated quite quickly whereas actually if they are used as needed for the breakthrough pain that is satisfactory for the patient and their family.
AD: That really goes back to the beginning about the level of understanding around breakthrough pain and just pain in general and management of pain. So lots still to do. In summary we probably all agree breakthrough pain is a significant problem for our patients, it’s probably not as well recognised as it should be and certainly not as well treated as it should be. We have some good options, some non-pharmacological options and some pharmacological options, but the right treatment for a specific patient depends on a proper assessment and equally support and reassessment from the multidisciplinary team. So I would just like to say thank you very much for your contribution.