Int J Clin Pharm DOI 10.1007/s11096-014-9921-1
CASE REPORT
Over compliance with capecitabine oral chemotherapy Jennifer Allen • Steve Williamson
Received: 21 March 2013 / Accepted: 6 February 2014 Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2014
Abstract Case A case study of a patient who over complied with adjuvant capecitabine monotherapy on several occasions is described. The patient suffered worsening side effects, predominantly palmar plantar erythrodysesthesia which resulted in dose reduction and delay. The patient had disregarded advice to stop taking the capecitabine as he perceived it as ‘‘important to fight his cancer’’. The patient refused review with a psychologist. Conclusion There is a lack of evidence regarding the issue of over compliance. Pharmacists should consider discussing patient’s attitudes towards taking their medication and its importance to them in treating their cancer. Tools that are used to assess non-compliance could be utilised to identify patients who over comply. Further research is required to gain further understanding of the psychological factors behind patient’s decisions to over comply with treatment. Keywords Adherence Adverse drug reactions Cancer Capecitabine Compliance Oral chemotherapy
Impacts on Practice •
•
Patients should feel responsible for ensuring they receive the required course(s) of chemotherapy. Pharmacist should help to ensure compliance. Pharmacists need to consider over compliance as well as under compliance when counselling patients on oral
•
anticancer medicines. In such cases, pharmacists need to consider referral to psychologists. There is a need for research into why cancer patients do not stop taking medicines or seek help when they experience treatment induced toxicity.
Introduction Oral chemotherapy is often cited as more patient friendly and convenient compared to intravenous administration. Oral chemotherapy allows the patient to self-administer their medication, reducing the need for venepuncture [1]. Over 80 % of patients would prefer to have their chemotherapy administered orally [2]. Patient counselling is imperative as the regimes involved can often be complicated, confer a high pill burden and result in side effects. This may lead to issues with adherence, which is often defined as the extent to which patients take medications as prescribed by a healthcare professional. [3] This in turn can adversely affect patient outcomes. Anecdotal evidence identified several patients in our organisation who had continued to take their oral chemotherapy after experiencing adverse side effects. These patients had been told in advance to stop treatment if these side effects occurred. These patients had been deemed to over comply with their chemotherapy regimen.
Case description J. Allen S. Williamson (&) Pharmacy Department, Northumbria Healthcare NHS Trust, North Shields, Tyne and Wear, UK e-mail: [email protected]
This case describes a 63 year old Caucasian male with a diagnosis of cancer of the rectum, staged as T2 N1 M0 (early stage disease, potentially curable with surgery and
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Int J Clin Pharm
chemotherapy) who over complied. After undergoing an anterior resection and colostomy, he was prescribed adjuvant capecitabine (Xeloda) oral chemotherapy. He had a past medical history of asthma, type two diabetes and cervical spondylosis. His medication history included tamsulosin, metformin, lercanidipine, bendroflumethiazide, simvastatin and amitriptyline. He had no known drug allergies. Baseline full blood counts, U&E and liver function tests were all normal prior to the initiation of chemotherapy. He was prescribed capecitabine 1,250 mg/m2 twice daily for 14 days every 21 days for 8 cycles in total. The patient was commenced on capecitabine twice daily, 2,300 mg morning and 2,450 mg evening, (based on a BSA of 1.85 m2). He attended the oncology ward as a day case every three weeks for monitoring. An oncology pharmacist assessed the patient’s symptoms and prescribed any supportive medications the patient needed. The pharmacist was also responsible for prescribing each cycle of chemotherapy. A medical review was scheduled at end of 8 cycles or sooner if the pharmacist needed to refer the patient to the oncologist. The patient tolerated the first cycle of capecitabine with minimal side effects. After completing the second cycle he reported feeling tired and nauseous, with intermittent diarrhoea via his stoma. He had taken metoclopramide and loperamide as required during the cycle. He was advised to take the metoclopramide regularly, which successfully controlled his nausea. At the end of cycle three the patient informed the pharmacist that his hands and feet were sore. On examination the patient had grade 1 palmar plantar erythrodysesthesia (PPE), with some numbness, tingling, swelling and erythema. This resulted in some discomfort but had not interfered with normal daily activities. He was counselled to use regular emollients, to monitor his hands and feet and to contact the oncology ward for further review if the symptoms worsened. At the next review, after cycle four, he reported feeling increasingly lethargic, with worsening PPE at grade 1/2. A treatment delay with a potential dose reduction of capecitabine was discussed with the patient; however he wanted to continue as planned. The next cycle of chemotherapy was supplied with counselling on the importance of stopping treatment and contacting the hospital for review if he experienced any worsening of symptoms. At the end of cycle five the patient’s PPE had progressed to grade 2, and he was suffering with very painful and swollen feet. During discussion, the patient disclosed that he had been unable to walk eight days after the start of cycle five. He reported that he had decided not to contact the hospital and had kept taking the capecitabine as it was ‘‘important to fight his cancer’’. Cycle six was delayed one week and the pharmacist reduced the capecitabine dose by
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20 %. The patient was angry and very reluctant to receive a reduced capecitabine dose (1,800 mg morning and 1,950 mg evening) as he felt this would be less effective. Additional counselling was required to explain that the full dose of chemotherapy could not be given due to the side effects experienced. The patient was offered a consultation with the department clinical psychologist, but declined. The patient returned to the oncology day unit after 1 week’s treatment interruption but his PPE symptoms had not resolved sufficiently so an additional weeks delay was required. The patient reported he had tolerated the reduced dose well and his PPE symptoms had improved to grade 1. The improvement continued throughout cycle seven, with symptoms graded at 0/1 due to mild swelling and redness at the end of the cycle. After cycle eight the patient attended for a final review. He explained that he had been struggling with nausea and mucositis during cycles seven and eight however did not mention the symptoms during review as he did not want to have a further dose reduction or treatment delay. The patient was reviewed by a Consultant Oncologist after completion of the planned eight cycles and was discharged from the oncology service after a CT scan confirmed there was no evidence of residual disease.
Discussion Literature reviews were conducted looking firstly at over compliance/over consumption of medicines in general, then more specifically to ascertain if over compliance with oral anticancer medication had been previously investigated. Many papers discussed patient barriers to compliance and reasons for non-adherence with oral anticancer regimens [4–6]. The problem of over compliance was rarely examined in the papers reviewed. It has been suggested that adherence rates of patients taking oral chemotherapy are similar to patients with chronic diseases, although cancer patients are often thought to be more highly motivated due to the nature of their disease [6]. When oral anticancer treatment is continued over a number of years, patients may become less compliant over time [5, 7]. Compliance may depend on type of treatment used, i.e. short cyclical courses or long term continuous treatment. A study of chronic myeloid leukaemia patients taking imatinib demonstrated poor adherence to treatment regimes as a strong predictor of reduced response rate [8]. However the effects of potential over compliance and adverse patient outcomes were not investigated. Nilsson et al. [7] found that 30 % of patients in the study had an oversupply of their medication, with a chemotherapy prescription refill rate of over 100 %. However the paper did not describe
Int J Clin Pharm
whether this group of patients had excess stock of medication due to over compliance or had experienced any adverse effects as a result. From this case we have seen that patients who hold strong beliefs in the importance of their medicine in treating their cancer may be at risk of over compliance. Our patient over complied resulting in worsening of side effects, treatment delay and dose reduction. The patient exhibited behaviour of hiding his symptoms, believing it was better to tolerate side effects and not have a dose reduction in order to make sure his treatment remained effective. Identifying this type of behaviour earlier and understanding their motivations could be critical in preventing over compliance. There are tools available to healthcare professionals to aid the identification of compliance issues with oral chemotherapy; however they aim to identify non-compliant patients [9]. There is a need for similar strategies to identify and support patients at risk of over compliance. The use of psychological assessment at an earlier stage could also have helped change our patient’s attitudes, however many patients do not wish to accept this intervention. Increasing pharmacists understanding of the psychological factors involved in providing medication counselling to this patient group could therefore help recognition of over compliance behaviour patterns. Pharmacists should consider discussing patient’s attitudes towards taking their medication and its importance to them in treating their cancer. This over compliance case was reviewed by our clinical team who agreed that a similar outcome would have been likely if a nurse or doctor had been reviewing the patient. The alternative of switching patient to 5-fluorouracil IV therapy was noted. The results of a promising on-going study into adherence with capecitabine may provide further insights into patient’s attitudes [10].
Conclusion The problem of potentially harmful over compliance with anticancer medicines needs further investigation.
Qualitative research regarding patient views on oral chemotherapy, treatment interruptions and dosage reductions should be undertaken in order to gain further understanding of the psychology and reasoning behind over compliance and the potential role pharmacists could play in preventing over compliance. Funding
None.
Conflicts of interest
None.
References 1. Simchowitz B, Shiman L, Spencer J, Brouillard D, Gross A, Connor M, et al. Perceptions and experiences of patients receiving oral chemotherapy. Clin J Oncol Nurs. 2010;14(4): 447–53. 2. Liu G, Franssen E, Fitch MI, Warner E. Patient preferences for oral versus intravenous palliative chemotherapy. J Clin Oncol. 1997;15:110–5. 3. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353:487–97. 4. Winkeljohn D. Adherence to oral cancer therapies: nursing interventions. Clin J Oncol Nurs. 2010;14(4):461–6. 5. Partridge AH, Wang PS, Winer PS, Avorn J, Weingart SN. Nonadherence to adjuvant tamoxifen therapy in women with primary breast cancer. J Clin Oncol. 2003;21:602–6. 6. Timmers L, Boons C, Mangnus D, Moes J, Swart E, Boven E, et al. The use of erlotinib in daily practice: a study on adherence and patients’ experiences. BMC Cancer. 2011;11:284. 7. Nilsson J, Andersson K, Bergkvist A, Bjo¨rkman I, Brismar A, Moen J. Refill adherence to repeat prescriptions of cancer drugs to ambulatory patients. Eur J Cancer Care. 2006;15(3):235–7. 8. Marin D, Bazeos A, Mahon F, Eliasson L, Milojkovic D, Bua M, et al. Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib. J Clin Oncol. 2010;28(14):2381–8. 9. Oncology Nursing Society. adherence to oral therapies for cancer: helping your patient stay on course toolkit. http://www.ons. org/ClinicalResources/OralTherapies/Toolkit. Accessed 5th December 2013. 10. Timmers L, Swart E, Boons C, Mangnus D, van de Ven PM, Godefridus P, et al. The use of capecitabine in daily practice: a study on adherence and patients’ experiences. Patient Prefer Adher. 2012;6:741–8.
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CASE REPORT
Over compliance with capecitabine oral chemotherapy Jennifer Allen • Steve Williamson
Received: 21 March 2013 / Accepted: 6 February 2014 Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2014
Abstract Case A case study of a patient who over complied with adjuvant capecitabine monotherapy on several occasions is described. The patient suffered worsening side effects, predominantly palmar plantar erythrodysesthesia which resulted in dose reduction and delay. The patient had disregarded advice to stop taking the capecitabine as he perceived it as ‘‘important to fight his cancer’’. The patient refused review with a psychologist. Conclusion There is a lack of evidence regarding the issue of over compliance. Pharmacists should consider discussing patient’s attitudes towards taking their medication and its importance to them in treating their cancer. Tools that are used to assess non-compliance could be utilised to identify patients who over comply. Further research is required to gain further understanding of the psychological factors behind patient’s decisions to over comply with treatment. Keywords Adherence Adverse drug reactions Cancer Capecitabine Compliance Oral chemotherapy
Impacts on Practice •
•
Patients should feel responsible for ensuring they receive the required course(s) of chemotherapy. Pharmacist should help to ensure compliance. Pharmacists need to consider over compliance as well as under compliance when counselling patients on oral
•
anticancer medicines. In such cases, pharmacists need to consider referral to psychologists. There is a need for research into why cancer patients do not stop taking medicines or seek help when they experience treatment induced toxicity.
Introduction Oral chemotherapy is often cited as more patient friendly and convenient compared to intravenous administration. Oral chemotherapy allows the patient to self-administer their medication, reducing the need for venepuncture [1]. Over 80 % of patients would prefer to have their chemotherapy administered orally [2]. Patient counselling is imperative as the regimes involved can often be complicated, confer a high pill burden and result in side effects. This may lead to issues with adherence, which is often defined as the extent to which patients take medications as prescribed by a healthcare professional. [3] This in turn can adversely affect patient outcomes. Anecdotal evidence identified several patients in our organisation who had continued to take their oral chemotherapy after experiencing adverse side effects. These patients had been told in advance to stop treatment if these side effects occurred. These patients had been deemed to over comply with their chemotherapy regimen.
Case description J. Allen S. Williamson (&) Pharmacy Department, Northumbria Healthcare NHS Trust, North Shields, Tyne and Wear, UK e-mail: [email protected]
This case describes a 63 year old Caucasian male with a diagnosis of cancer of the rectum, staged as T2 N1 M0 (early stage disease, potentially curable with surgery and
123
Int J Clin Pharm
chemotherapy) who over complied. After undergoing an anterior resection and colostomy, he was prescribed adjuvant capecitabine (Xeloda) oral chemotherapy. He had a past medical history of asthma, type two diabetes and cervical spondylosis. His medication history included tamsulosin, metformin, lercanidipine, bendroflumethiazide, simvastatin and amitriptyline. He had no known drug allergies. Baseline full blood counts, U&E and liver function tests were all normal prior to the initiation of chemotherapy. He was prescribed capecitabine 1,250 mg/m2 twice daily for 14 days every 21 days for 8 cycles in total. The patient was commenced on capecitabine twice daily, 2,300 mg morning and 2,450 mg evening, (based on a BSA of 1.85 m2). He attended the oncology ward as a day case every three weeks for monitoring. An oncology pharmacist assessed the patient’s symptoms and prescribed any supportive medications the patient needed. The pharmacist was also responsible for prescribing each cycle of chemotherapy. A medical review was scheduled at end of 8 cycles or sooner if the pharmacist needed to refer the patient to the oncologist. The patient tolerated the first cycle of capecitabine with minimal side effects. After completing the second cycle he reported feeling tired and nauseous, with intermittent diarrhoea via his stoma. He had taken metoclopramide and loperamide as required during the cycle. He was advised to take the metoclopramide regularly, which successfully controlled his nausea. At the end of cycle three the patient informed the pharmacist that his hands and feet were sore. On examination the patient had grade 1 palmar plantar erythrodysesthesia (PPE), with some numbness, tingling, swelling and erythema. This resulted in some discomfort but had not interfered with normal daily activities. He was counselled to use regular emollients, to monitor his hands and feet and to contact the oncology ward for further review if the symptoms worsened. At the next review, after cycle four, he reported feeling increasingly lethargic, with worsening PPE at grade 1/2. A treatment delay with a potential dose reduction of capecitabine was discussed with the patient; however he wanted to continue as planned. The next cycle of chemotherapy was supplied with counselling on the importance of stopping treatment and contacting the hospital for review if he experienced any worsening of symptoms. At the end of cycle five the patient’s PPE had progressed to grade 2, and he was suffering with very painful and swollen feet. During discussion, the patient disclosed that he had been unable to walk eight days after the start of cycle five. He reported that he had decided not to contact the hospital and had kept taking the capecitabine as it was ‘‘important to fight his cancer’’. Cycle six was delayed one week and the pharmacist reduced the capecitabine dose by
123
20 %. The patient was angry and very reluctant to receive a reduced capecitabine dose (1,800 mg morning and 1,950 mg evening) as he felt this would be less effective. Additional counselling was required to explain that the full dose of chemotherapy could not be given due to the side effects experienced. The patient was offered a consultation with the department clinical psychologist, but declined. The patient returned to the oncology day unit after 1 week’s treatment interruption but his PPE symptoms had not resolved sufficiently so an additional weeks delay was required. The patient reported he had tolerated the reduced dose well and his PPE symptoms had improved to grade 1. The improvement continued throughout cycle seven, with symptoms graded at 0/1 due to mild swelling and redness at the end of the cycle. After cycle eight the patient attended for a final review. He explained that he had been struggling with nausea and mucositis during cycles seven and eight however did not mention the symptoms during review as he did not want to have a further dose reduction or treatment delay. The patient was reviewed by a Consultant Oncologist after completion of the planned eight cycles and was discharged from the oncology service after a CT scan confirmed there was no evidence of residual disease.
Discussion Literature reviews were conducted looking firstly at over compliance/over consumption of medicines in general, then more specifically to ascertain if over compliance with oral anticancer medication had been previously investigated. Many papers discussed patient barriers to compliance and reasons for non-adherence with oral anticancer regimens [4–6]. The problem of over compliance was rarely examined in the papers reviewed. It has been suggested that adherence rates of patients taking oral chemotherapy are similar to patients with chronic diseases, although cancer patients are often thought to be more highly motivated due to the nature of their disease [6]. When oral anticancer treatment is continued over a number of years, patients may become less compliant over time [5, 7]. Compliance may depend on type of treatment used, i.e. short cyclical courses or long term continuous treatment. A study of chronic myeloid leukaemia patients taking imatinib demonstrated poor adherence to treatment regimes as a strong predictor of reduced response rate [8]. However the effects of potential over compliance and adverse patient outcomes were not investigated. Nilsson et al. [7] found that 30 % of patients in the study had an oversupply of their medication, with a chemotherapy prescription refill rate of over 100 %. However the paper did not describe
Int J Clin Pharm
whether this group of patients had excess stock of medication due to over compliance or had experienced any adverse effects as a result. From this case we have seen that patients who hold strong beliefs in the importance of their medicine in treating their cancer may be at risk of over compliance. Our patient over complied resulting in worsening of side effects, treatment delay and dose reduction. The patient exhibited behaviour of hiding his symptoms, believing it was better to tolerate side effects and not have a dose reduction in order to make sure his treatment remained effective. Identifying this type of behaviour earlier and understanding their motivations could be critical in preventing over compliance. There are tools available to healthcare professionals to aid the identification of compliance issues with oral chemotherapy; however they aim to identify non-compliant patients [9]. There is a need for similar strategies to identify and support patients at risk of over compliance. The use of psychological assessment at an earlier stage could also have helped change our patient’s attitudes, however many patients do not wish to accept this intervention. Increasing pharmacists understanding of the psychological factors involved in providing medication counselling to this patient group could therefore help recognition of over compliance behaviour patterns. Pharmacists should consider discussing patient’s attitudes towards taking their medication and its importance to them in treating their cancer. This over compliance case was reviewed by our clinical team who agreed that a similar outcome would have been likely if a nurse or doctor had been reviewing the patient. The alternative of switching patient to 5-fluorouracil IV therapy was noted. The results of a promising on-going study into adherence with capecitabine may provide further insights into patient’s attitudes [10].
Conclusion The problem of potentially harmful over compliance with anticancer medicines needs further investigation.
Qualitative research regarding patient views on oral chemotherapy, treatment interruptions and dosage reductions should be undertaken in order to gain further understanding of the psychology and reasoning behind over compliance and the potential role pharmacists could play in preventing over compliance. Funding
None.
Conflicts of interest
None.
References 1. Simchowitz B, Shiman L, Spencer J, Brouillard D, Gross A, Connor M, et al. Perceptions and experiences of patients receiving oral chemotherapy. Clin J Oncol Nurs. 2010;14(4): 447–53. 2. Liu G, Franssen E, Fitch MI, Warner E. Patient preferences for oral versus intravenous palliative chemotherapy. J Clin Oncol. 1997;15:110–5. 3. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353:487–97. 4. Winkeljohn D. Adherence to oral cancer therapies: nursing interventions. Clin J Oncol Nurs. 2010;14(4):461–6. 5. Partridge AH, Wang PS, Winer PS, Avorn J, Weingart SN. Nonadherence to adjuvant tamoxifen therapy in women with primary breast cancer. J Clin Oncol. 2003;21:602–6. 6. Timmers L, Boons C, Mangnus D, Moes J, Swart E, Boven E, et al. The use of erlotinib in daily practice: a study on adherence and patients’ experiences. BMC Cancer. 2011;11:284. 7. Nilsson J, Andersson K, Bergkvist A, Bjo¨rkman I, Brismar A, Moen J. Refill adherence to repeat prescriptions of cancer drugs to ambulatory patients. Eur J Cancer Care. 2006;15(3):235–7. 8. Marin D, Bazeos A, Mahon F, Eliasson L, Milojkovic D, Bua M, et al. Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib. J Clin Oncol. 2010;28(14):2381–8. 9. Oncology Nursing Society. adherence to oral therapies for cancer: helping your patient stay on course toolkit. http://www.ons. org/ClinicalResources/OralTherapies/Toolkit. Accessed 5th December 2013. 10. Timmers L, Swart E, Boons C, Mangnus D, van de Ven PM, Godefridus P, et al. The use of capecitabine in daily practice: a study on adherence and patients’ experiences. Patient Prefer Adher. 2012;6:741–8.
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