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Enzyme replacement in advanced pancreatic cancer: patient perceptions
  1. Amanda Landers1,
  2. Clare McKenzie2,
  3. Suzanne G Pitama3 and
  4. Helen Brown2
  1. 1 Department of Medicine, University of Otago, Christchurch, New Zealand
  2. 2 Hospice and Palliative Care, Nurse Maude Association, Christchurch, New Zealand
  3. 3 Māori Indigenous Health Institute, University of Otago, Christchurch, New Zealand
  1. Correspondence to Dr Amanda Landers, Department of Medicine, University of Otago, Christchurch, New Zealand; Amanda.Landers{at}otago.ac.nz

Abstract

Purpose Advanced pancreatic cancer has a universally poor survival rate. Patients frequently develop malabsorption that requires pancreatic enzyme replacement therapy (PERT). This study explores the experience of patient engagement with PERT and how the medication is taken and tolerated.

Methods Participants with advanced pancreatic cancer requiring PERT were interviewed after referral to a specialist palliative care team. An inductive analysis was used to code the data. Theoretical sufficiency was reached after 12 participants.

Results Four themes emerged from the interviews-patient context, health literacy, relationship to food and experience of taking the pancreatic enzymes. Respondents brought their own life experiences into the clinical encounter when told of the diagnosis. Patients had high levels of understanding and engagement with the diagnosis and treatment, understood the benefits of PERT in digestion and tolerated the medication well.

Conclusions Patients with metastatic pancreatic cancer understand the life-limiting nature of their illness. They want to participate in their healthcare decisions and are capable of complex medication titration when given good explanations and they experience benefits. PERT should be offered to these patients by a team of knowledgeable health professionals with good communication skills that can continue to support and review their needs.

  • Pancreatic
  • Education and training
  • Communication

Data availability statement

Data are available upon reasonable request. Data are not in a repository state. The data are available from lead author on request but will be de-identified. The interview schedule would be available. Reuse in a publishable format is not permitted. Author can be contacted on Amanda.landers@otago.ac.nz.

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Introduction

Pancreatic cancer (PC) consistently continues to have a globally poor prognosis despite cutting-edge medicine and the age of rapidly emerging immunotherapy cancer treatments. In New Zealand, PC has the lowest 1 year cancer survival rate of 24.8%, with only 8.2% of patients alive at 5 years.1 The lack of disease-modifying treatments and curative options has lead cancer care teams to focus on other ways to improve quality of life for these patients and their families.

One of the hallmarks of PC is weight loss.2–4 Anorexia is a common mechanism for weight loss and may be caused by poorly managed pain, nausea, early satiety and tumour hormone secretion.5 Another cause of weight loss is altered metabolism leading to a catabolic state.6 Malabsorption is a major feature in PC with studies showing rates between 68% and 92% in patients with PC.7–9 This may be due to direct parenchymal loss secondary to malignancy in combination with ductal obstruction.10 Weight loss is one of the most distressing features of the disease, with profound effects on a person’s psychological well-being.11

Malabsorption causes symptoms such as bloating, wind, diarrhoea, steatorrhoea and abdominal pain.12 Studies have shown that the vast majority of patients diagnosed with PC have malabsorption at diagnosis2 8 9 13; yet treatment with pancreatic enzyme replacement therapy (PERT) remains suboptimal across the world.14 15 It has been shown that PERT is a well-tolerated, safe and effective therapy for symptoms of malabsorption.16 The enzyme replacement has been reported to have positive effects on quality of life and is recommended by international guidelines; yet only a small number of patients are offered this treatment.14 17 PERT has not only been shown to improve weight loss, symptoms and quality of life but may also prolong survival.17 18

There is a growing emphasis in the literature of the importance of the patient experience within health. Until recently, specific diseases, increasingly sophisticated medical technology and therapies drove system design. However, healthcare delivery can be adapted and improved by the use of patient perceptions and experiences. Patients want to be informed about their diagnosis, prognosis and treatment options so they can better participate in decisions about their care.14 19 Patient adherence to treatment has been found to correlate with the health literacy competence of the clinician.20 21 Positive experiences resulting in adherence have implications for better health outcomes.22

This study aims to explore the perceptions of individuals with PC receiving their diagnosis, how the treatment option of PERT was communicated by clinicians and the experience of taking the medication. Ultimately, this may help understand the barriers to treatment and inform health practitioners in their interactions with patients diagnosed with PC.

Methods

This study was undertaken in the Canterbury region of New Zealand, one of the largest in the country. It is situated in the South Island of New Zealand where a large proportion of the population identify as New Zealand European or of European ethnicity (88.4% census data). The majority of specialist services in New Zealand are delivered within a free public health system which serves people from all socio-economic backgrounds. Community-based specialist palliative care with dedicated medical input is uncommon but exists in the Canterbury district. The specialist palliative care team (SPCT) has developed expertise over the last 8 years in the area of PC and malabsorption. This team has strong links with the oncology and surgical specialties which facilitates the early referral of patients with PC. This allows for timely education and commencement of PERT.

The SPCT dietitian prioritised patients with PC and saw them within two to three working days. An assessment for malabsorption was undertaken and determined if PERT was an appropriate treatment. Patients were recruited into the study if they were over 18 years, had a Palliative Performance Score of at least 60% or above,23 had not commenced PERT and were able to give consent to participate in English.

The SPCT dietitian provided an information sheet to all potential participants during an initial home visit and gained written consent. Patients were then commenced on pancrelipase 25 000 IU (Creon 25000, Abbott, Germany) with a starting dose of 50 000 IU per meal and 25 000 IU per snack. The average fat content of a diet was calculated and participants were counselled not to avoid fat. The starting dose was titrated by the patient on the basis of a 24-hour recall and discussed with the dietitian. A reassessment tended to occur after 1 week and 3 weeks after commencement. If there were ongoing malabsorption symptoms or increased food intake, the Creon dose was escalated to meet the fat requirements. Not all patients had a proton pump inhibitor prescribed to reduce gastric acid. Baseline demographic data were collected on a data sheet. A research nurse (CM) interviewed all participants in their own homes. These interviews took between 20 and 60 min and were audiotaped and transcribed verbatim.

The research team drew on current literature to develop a semi-structured interview schedule. This comprised seven questions that explored aspects of quality of life, illness perceptions, understanding of diagnosis and patient experience related to PERT. After the first few interviews, it was noted that patients had a very clear memory of receiving the news of the diagnosis, including the date and context of delivery. Therefore in subsequent interviews, a further question regarding the timing and delivery of diagnosis was included.

Theoretical sufficiency was met when the authors identified no new codes or categories emerging from the 11th and 12th interview. Therefore no further participants were sought after the completion of the 12th discussion.

Data analysis

The use of qualitative methodology to explore patient experiences is well documented.24–27 To achieve the intended study aims, inductive analysis was used to encode and order the qualitative data.24 25 Inductive analysis is data-driven, and determines that findings are directly derived from the data (patient voice).26 Coding was undertaken collaboratively between authors (AL, SGP, HB and CM), where criteria for all codes, categories and themes were discussed, negotiated and agreed on by consensus. NViVo V.12 was used to undertake peer review and complete the analysis.

Structural coding was used for the first cycle of coding to initially order the data.27 This involved the search for shared narrative within the data specifically about the patient’s experience of using PERT. Descriptive analysis was then undertaken to explore the richness and diversity of the data.27

The second cycle of coding drew on the method of theoretical coding to determine the more explicit relationships between codes, to cluster those that described a similar phenomenon, in which they were then re-organised into categories. These categories were reviewed in order to identify similar characteristics, and were further organised as four themes; patient context, health literacy, relationship with food and experience of PERT.

Results

Sixteen participants consented to participate in the study and a total of 12 completed interviews. Two participants withdrew due to deterioration of health and two died during the early stages of the study. Participants ranged in age from 56 to 79 years, with Palliative Performance Scores between 60% and 90% (table 1).

Table 1

Patient characteristics (n=12)

The four themes identified were: (1) patient context which highlights previous knowledge and family dynamics, (2) health literacy of cancer and the effect on digestion, (3) relationship to food following commencement of PERT, (4) experience of taking PERT. These four themes will now be discussed in more detail.

Patient context

Participants’ constructs, informed by previous knowledge and family connections, should be seen as pivotal by clinicians in tailoring communication and future planning to enhance the patient experience.

Most participants were able to recall the exact day of diagnosis with clarity. This included both how it was communicated and their emotional response to this information. When participants had previous family experiences of cancer, this influenced what they understood about possible prognosis and potential outcomes. However, the clinician often did not explore previous experience, and therefore conversations around the diagnosis tended to begin at a base level and were not tailored to the participants’ health literacy level. Participants reported feeling overwhelmed by the diagnosis and found it too difficult to try and process any further information about future treatment.

Both my parents died of cancer, and my mother 59 with lung cancer - we thought but it was lymphoma and my father at 35 with a brain tumour yes so I always dreaded to be 59 and at my 60th I was just pleased to get to 60 and live past the age that my mother did so it wasn't a total surprise when I hear I had cancer because I always thought I would get it and die young or something (Participant 1)

Being a nurse myself I knew that if it was pancreatic as well as the liver I certainly wasn't going to have surgery and they quickly put me right about that and that was good I had already worked that out (Participant 2)

Participants noted that the navigation of family expectations was complex. This included different family opinions around engagement with treatment and proposed life changes. It also involved participants downplaying pain and symptoms to protect their families from the realities of a life-limiting illness. Roles within relationships also changed within each patient context, this occurred in relation to food and medication. Family members took a more active role to monitor treatment and the participant lost elements of their autonomy.

Oh yea - the changes, it's an interesting, it's interesting - in thinking ok - priorities, what's happened, looking at your priorities, make some changes ah, life-changing, what are you going to do. And I've been given some options ah and of course conflict within the family, what you'd like to do, what they feel ought to be done. (Participant 3)

The girls have been giving it (PERT) to me and ticking it off I used to do it myself but I got very muddled (Participant 4)

Health literacy

The advanced level of health literacy in these participants allowed them to interpret and use the information about PERT effectively. This enabled a high level of commitment and self-management of PERT with the potential for better outcomes.

Participants exhibited a comprehensive understanding of the terminal nature of the diagnosis. They recalled the detailed information, often given in picture form, which helped them to understand their symptoms and the extent of their disease. It enabled them to reconcile the diagnosis of advanced PC with the futility of treatment options. It was almost universal that participants knew they were going to die.

They've told me that at this point it's inoperable, umm and because the pancreas, the cancer in the pancreas is around an artery it's too dangerous to try and take any of it out. Umm chemo may reduce it enough to operate but it’s unlikely. Umm and yea so, and yea so they've told me I have months rather than years to live (Participant 5)

So I've had um explained to me what it is lots of diagrams and pictures about where my tumour is and where it has progressed and the risks and options of treatment, essentially there were no treatments where they outweighed the risks and the probable course of the disease so quite a lot, I think I've been well informed had really good information.(Participant 6)

It was evident from participants that the information regarding PERT and the way it was delivered resulted in an advanced level of health literacy. They were able to describe the need for enzyme replacement therapy and its role in digestion. The participants were also able to recall having received written instructions, information leaflets and education. This high level of engagement led to an increased sense of control and self-management, allowing them to titrate their medication to the fat content of their diet. The ability to control the medication themselves increased the likelihood of better symptom management.

Um well basically the pancreas doesn’t produce the enzymes the thousands of enzymes that come across every time we eat so this replaces that so basically any time I put food in my mouth - I love aeroplane lollies anything sweet, I’m eating those now um and that this replaces the enzymes basically and toileting and everything has just been perfect.(Participant 1)

Firstly X told me that is how you deal with it - wrote out the instructions and umm said if you want to get the most out of your food that's what you do. If you get the most out of your food you keep that weight on and keeping weight on ah is pretty important. (Participant 3)

Some of the participants volunteered that they had researched further into PERT, which confirmed the information they had already been provided. The high level of commitment to PERT was evident by the creative ways they used to ensure the medication was not forgotten, with family and friends to support them.

I found more out on the internet - I’m a great googler and researcher and I got this, and I was a bit sorry actually that some of this wasn’t given out at the time when I started. So that’s what I’ve printed out off the computer and that fully explained it and also the information I have picked up off pancreas cancer sites (Participant 1)

I would say it has been one of the hardest things about it – yea that’s a biggie, we have signs at home but I got used to seeing the signs so walked through them we had signs on the fridge –never really worked. (Participant 6)

Relationship to food

Malabsorption associated with advanced PC significantly changes the relationship patients have with food. PERT normalises and improves the eating experience which, in turn, positively impacts quality of life.

The participants described a changed relationship with food. Before PERT, patients self-moderated their food choices due to unpleasant symptoms. They had lost the enjoyment of food, especially their favourites. This led them to opt out from special occasions and limited the range of food options in day-to-day living. The commencement of PERT allowed greater freedom of food choices and increased normalisation of eating. Participants also mentioned the physical and emotional benefits of PERT. Physical improvements included increased appetite, reduction in abdominal pain and bloating, and normalisation of bowel habit. It also improved emotional well-being, feeling that they could self-manage their own symptoms.

Yesterday we went out with some friends and I actually had a hamburger and some curly fries - so I think I had 3 at the start and another one sort of when I was into the chips and it was good - yea, no, I never felt sick. yea I think they 're really good. (Participant 5)

Umm within 2 or 3 days of starting to take it I felt a lot more energetic and alert and alive and could focus and concentrate before I couldn't - on anything. And umm it has given me an appetite. (Participant 7)

The most significant issue that impacts on patients’ quality of life with PC is dysfunctional digestion which leads to symptoms of bloating, abnormal bowel habit and abdominal discomfort. The steatorrhoea profoundly affected how they felt about themselves, personal hygiene and the loss of spontaneity. Participants described the improvement in their bowel habit after starting PERT as life-changing.

I came home and I was so tight here under my bra line and I was going out that evening for a luncheon with some Zonta ladies and I just came home and took all my clothes off and put some soft clothes on and just lay on the bed for an hour before I went out and got dressed and also I had this diarrhoea - steatorrhoea I think it is and smelly -ooh so smelly like an old lady I thought I would have to start carrying wipes with me to clean myself and then X came to see me on the Thursday and put me on the Creon and after that all the symptoms stopped. (Participant 1)

Experience of taking pancreatic enzymes

PERT was well-tolerated almost universally despite the size and number of the capsules. Only one patient reported difficulty. Patients and their families adjusted well to the change in routine around mealtimes and eating. Participants depended on carers to remind them to take the enzymes at appropriate times.

The PERT capsules are large with coated beads inside the gelatin shell. The number needed to take at each mealtime was dependent on the fat content. Patients soon understood the titration aspect of enzyme replacement and displayed a high level of engagement with the complicated process.

No - slid right down - that's not been an issue. (Participant 3)

I'm getting quite good now at knowing how many I probably need for what I'm eating so um in that respect it's really, really good, and I wouldn't be without them. My husband calls them my miracle tablets. (Participant 5)

The benefits experienced seemed to go beyond just the correction of malabsorption. There appeared to be improvements, not just with physical symptoms such as energy and appetite, but also psychologically for both patient and family. This was central to the overall impact PERT had on quality of life.

Certainly the creon has changed my life completely (Participant 1)

Patients and families adapted to the integration of PERT into their daily lives. However, many participants reported significant difficulty initially remembering the medication at the correct times. It was common for patients to miss doses and they employed various strategies to correct this such as signs on the fridge. One participant felt guilty about missing a dose and others described feeling as if PERT was a daily reminder of their cancer diagnosis. Another respondent noticed an immediate worsening of symptoms after forgetting a dose. They relied heavily on family members to help prompt them at mealtimes and to ensure they always had a supply when socialising.

It's just remembering to take it sort of every time before you eat - that's my worst thing. I don't know if it's because I'm going senile or what I don't know (haha). But yea I struggle - I pick up my food and wander over here and Nola says have you taken your Creon yet? and I say no so I put it all down again and go take the Creon. Yea it's just remembering it is my biggest problem. (Participant 8)

Although I know I need to take them they are a daily reminder of why I need to take them - because I've got pancreatic cancer. (Participant 1)

Discussion

The majority of patients with PC have malabsorption of their food at diagnosis.8 28 Globally, these patients are not started on enzyme replacement for symptom management, or the wrong dose is commenced.14 15 Patients and their families often do not understand why they are taking the medication, leaving them disengaged from the treatment and less likely to adhere to their drug regime.29 They begin to avoid foods that cause harm, leading to rapid weight loss and an unhealthy relationship with food.9 Our study focused on the evaluation of good communication about the diagnosis, timely referrals to a specialist palliative care service with expertise in this area, the use of tailored resources about PERT, education to both patient and family and both the commencement and tolerability of PERT. The four themes that emerged from the study highlight the importance of previous experiences patients have of ill-health, the high health literacy that can be achieved with the right delivery of information, the change in the relationship to food after PERT commencement and that PERT is well-tolerated by most people.

Gooden et al studied patients with PC and investigated their unmet psychosocial needs.29 They showed that the biggest gap in knowledge and in the ability to cope for these patients was the management of their malabsorption symptoms. A study published in 2012 evaluated the use of PERT postoperatively and found the majority were undertreated.15 This 2012 study indicated that surgeons and gastroenterologists did not achieve a satisfactory treatment outcome and physicians were not well-educated on this medication. Even with good theoretical knowledge, PERT requires intensive monitoring by health professionals to train patients in the titration of the medication.

Most patients want to be given relevant information about their diagnosis, prognosis and treatment possibilities.19 Patients also want to participate in the decisions about their healthcare. Schildmann et al interviewed 12 patients with PC and found all of them understood the poor prognosis and several participants mentioned examples of previous personal experiences.19 This is similar to our findings of the importance of patient context and the knowledge that already exists before engaging in the clinical encounter.

It has been recognised that the exploration of the patient experience can change practice in healthcare. The patient perspective directly measures key aspects of outcomes like patient-health professional communication. If communication is suboptimal, patient adherence is likely to be affected.20 Our study shows patient adherence being improved by good patient-provider communication.21 22 Even further, adherence then leads to better clinical outcomes and good self-management, a desire for more information and creative strategies by patients to remember the medication. Increased knowledge and adherence to PERT, then a clinical improvement, cements the commitment to the regime. Unlike Gordon et al who found a lack of information was the key concern for their participants, leading to incorrect assumptions and misperceptions, our respondents showed high levels of health literacy and therefore self-management. Gordon et al also found that the need for information was dynamic and needed to be reviewed and tailored by the health professional.30

One study found that most patients considered the treatment regimen of approximately eight large-sized capsules a day burdensome.31 This finding is in contrast to our study who found most tolerated the medication well. Patients preferred taking ownership of their condition by self-titrating the medication to their diet. They also understood the safety and maximum dose of their enzyme replacement. This is in contrast to many other medications where titration is required through direction by a health professional. Food is central to our way of life. It is part of every social interaction, celebration and keeps people involved in the community. Patients weigh up the benefits of improved relationships with food against the inconvenience of taking capsules. This study showed that for our participants the benefits outweighed the burdens.

Strengths and limitations of this study

Our study was conducted in one centre although across settings. It included a multidisciplinary team with expertise in PC and malabsorption. However, the knowledge within the team has been achieved over many years and with a special interest in this area of supportive cancer care. Other centres and countries may not have this knowledge or level of collaboration between specialties and organisations.

Implications for future research, policy and practice

In cancer care, different services must collaborate and communicate with each other and the patients in ways that are meaningful for better health outcomes. This study shows the possible benefits from a system that navigates people through their diagnosis, treatment options and medication. It is imperative that training in the importance of PERT in PC is taught to surgeons, physicians, general practitioners and dietitians. Future research could explore a PC malabsorption pathway that ensures there is certainty in offering PERT to all appropriate patients.

Conclusion

Patients with advanced PC were referred to a community-based palliative care service with expertise in malabsorption. These patients have unique symptoms and need extra information and knowledge about their changing relationship with food and digestion. They need an engaged and knowledgeable healthcare team who can guide them with enzyme replacement in a way that supports them with self-management. Patients want to have the knowledge and they retain the information if it is given in a way they understand. They may enlist the help of family to support and prompt. The patients did not find the tablets burdensome once they knew their purpose and for many, their symptoms improved. The challenge to health providers who care for patients with advanced PC is the acknowledgement that this is a crucial part of standard treatment. Responsibility for this treatment must be designated to a lead health professional who raises awareness of enzyme replacement, educates patients and families, and monitors the outcomes. In light of the universally poor outcomes patients with PC continue to have, it is critical to maximise supportive measures for quality of life.

Data availability statement

Data are available upon reasonable request. Data are not in a repository state. The data are available from lead author on request but will be de-identified. The interview schedule would be available. Reuse in a publishable format is not permitted. Author can be contacted on Amanda.landers@otago.ac.nz.

Ethics statements

Patient consent for publication

Ethics approval

Ethical approval for this study was obtained by the University of Otago Human Ethics Committee (Health H16/038).

Acknowledgments

This work was supported by the Nurse Maude Hospice Palliative Care Service, Christchurch, New Zealand. We gratefully thank Dr Matthew Strother for his work in helping shape the design of this study. The authors acknowledge the patients and families who participated in this work.

References

Footnotes

  • Contributors Initial research design and interview questionnaire were carried out by CM, AL, SGP and HB. CM was involved in data collection. CM, AL, SGP and HB were part of the data analysis and writing of the article. CM, AL, SGP and HB read and approved of the final draft. AL is responsible for overall content as guarantor.

  • Funding This study was funded by the Otago Medical School Trust Fund, University of Otago, Christchurch, New Zealand.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.