530180 research-article2014
PMJ0010.1177/0269216314530180Palliative MedicineLowery et al.
Case Report
The use of aprepitant in a case of refractory nausea and vomiting
Palliative Medicine 2014, Vol. 28(7) 990–991 © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0269216314530180 pmj.sagepub.com
Lucy Lowery, Inga Andrew, Sarah Gill and Mark Lee
Abstract Background: This case report describes a patient whose refractory nausea and vomiting significantly improved with the use of aprepitant, a neurokinin receptor antagonist currently only licensed for short-term use in chemotherapy-induced nausea and vomiting. Case presentation: A patient with breast cancer and meningeal metastases had an 18-month history of nausea and vomiting refractory to a number of antiemetics commonly used in palliative care. The nausea and vomiting resolved after receiving two doses of the drug aprepitant. Case management and outcome: Maintenance antiemetic treatment with aprepitant was continued over a 5-month period with no recurrence of nausea and vomiting, and no observed side effects. Conclusions: Aprepitant has a potential role as an antiemetic for refractory symptoms within the palliative-care setting. Keywords Aprepitant, neurokinin receptor antagonist, nausea, vomiting, refractory
Background Nausea and vomiting (NV) are common symptoms encountered by the palliative-care population, and are often very distressing for the patient. Despite the large number of antiemetics currently available in palliative care, NV can still be refractory in a small number of cases. Aprepitant is a relatively new antiemetic drug, and its mechanism of action is as a potent neurokinin (NK1) antagonist. NK1 receptors are found at multiple sites within the central nervous system, including both the chemoreceptor trigger zone and the vomiting centre. Both of these areas are located in the brainstem and are important locations in the NV pathway. Aprepitant is currently only licensed for short-term use in chemotherapy-induced NV (CINV). Current evidence shows that the addition of aprepitant to the standard antiemetic regime (5-hydroxytryptamine (5HT3) antagonist plus dexamethasone) improves symptoms of both acute and delayed phase CINV by around 18%.1 Evidence for the use of aprepitant as an antiemetic outside of CINV is limited. A small case control study showed improvement in post-operative NV (PONV) with aprepitant use compared to combination treatment (ondansetron, dexamethasone and additional antiemetics) following orthopaedic surgery, in which epidural morphine was felt to be the main cause of NV.2 Aprepitant has further shown to significantly improve PONV after gynaecological surgery when compared to no antiemetic treatment.3
Two single case studies reported the use of aprepitant for NV related to gastroparesis. Both describe patients with severe refractory symptoms of NV who showed a dramatic response to aprepitant within the first two doses. The drug was used for 2 and 4 months, and no side effects were reported.4,5 Due to a current lack of evidence, its potential role within a palliative-care setting is not clear. We describe a case of its effective use in refractory NV of uncertain aetiology in a patient with breast cancer with meningeal metastases.
Case presentation A 27-year-old female was diagnosed with invasive lobular breast carcinoma with local lymphadenopathy and underwent surgery followed by adjuvant chemoradiotherapy. A total of 15 months after completing this initial treatment, she was diagnosed with meningeal metastases on computed tomography scan after she presented with headaches and
St Benedict’s Hospice, Sunderland, UK Corresponding author: Mark Lee, St Benedict’s Hospice, St Benedict’s Way, Ryhope, Sunderland, SR2 0NY, UK. Email: [email protected]
Downloaded from pmj.sagepub.com at GEORGIAN COURT UNIV on April 12, 2015
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Lowery et al. NV. She underwent further chemotherapy, and a ventriculoperitoneal shunt was inserted after magnetic resonance imaging (MRI) revealed obstructive hydrocephalus. She subsequently had an 18-month history of NV which persisted despite treatment with a variety of antiemetics (cyclizine, haloperidol, levomepromazine, olanzapine, metoclopramide, domperidone, and dexamethasone inclusive), and utilising both oral and subcutaneous routes of administration. These had been tried systematically and based on careful consideration of the cause of the NV and the potential receptors involved. An MRI was arranged some months later following a generalised seizure and showed progressive meningeal disease but no evidence of recurrent hydrocephalus. As a result of her persistent NV, she was admitted to an inpatient palliative-care setting for a period of assessment. Due to the prolonged history of her symptoms, it was felt that her NV may have an anticipatory element, but no improvement was seen with the use of benzodiazepines or with psychological intervention. Furthermore, previous trials of high-dose dexamethasone (up to 16 mg once daily) failed to improve her NV. Due to exhaustion of all commonly used treatments and the persistence of her symptoms the decision was made (after discussion with the patient) to try aprepitant.
Case management and outcome Aprepitant is an oral medication and is licensed to be given as a 3-day course in association with chemotherapy. Usual practice is to give a loading dose of 120 mg followed by 2-day maintenance dose of 80 mg. It was anticipated that the drug would be used over a longer period and as such a once daily dose of 80 mg was given. Daily Palliative Care Assessment Tool (PACA) scores6 were recorded to assess her symptoms of NV. Before commencing aprepitant, she consistently scored her NV as a 2 or 3 (moderately affecting or dominating her day). After two doses of aprepitant, her PACA score reduced to 0 (symptom absent) and to date her symptoms of NV remain controlled after 5 months on treatment. Furthermore, over this time period her previous antiemetics have been withdrawn without any recurrence of NV. Overall, the use of aprepitant markedly improved her quality of life, and there were no definite or severe side effects noted with its long-term use. Common side effects such as hiccups, dyspepsia, constipation, headache, anorexia, and fatigue were monitored by health-care professionals as part of her holistic needs assessment.
Conclusion Aprepitant is a member of a relatively new class of antiemetic drugs, and as a result, it is not used routinely within the palliative-care setting. Although the precise mechanism for NV is not clear, this case demonstrates the
effectiveness of the drug in a patient with refractory symptoms. On reviewing the literature, there appears to be only sparse use of this drug for NV outside of its CINV licence. The only use of aprepitant for refractory NV in a palliativecare setting which was demonstrated in our search was located on the Palliativedrugs.com discussion board. Three single cases of its successful use for refractory NV in malignant disease were reported; however, an underlying cause for NV in these cases was not suggested.7 Interestingly, in our case and in previous case reports of refractory NV in patients with both malignancy and gastroparesis, the dramatic benefit of aprepitant has been seen after only 1–2 doses, and has regularly led to the withdrawal of multiple alternative medications and treatments.4,5 We believe that aprepitant could be an alternative antiemetic for patients with refractory NV who have demonstrated poor response to more traditional antiemetics used in palliative care. Further research into its effectiveness in managing NV unrelated to chemotherapy, as well as data regarding its use long term, would be beneficial. Acknowledgement The patient gave permission for this report to be published.
Declaration of conflicting interests The authors report no conflicts of interest.
Funding This report received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
References 1. Dos Santos LV, Souza FH, Brunetto AT, et al. Neurokinin-1 receptor antagonists for chemotherapy induced nausea and vomiting: a systematic review. J Clin Onc 2013; 31(15): 1280–1292. 2. Hartrick CT, Tang Y, Hunstad D, et al. Aprepitant vs. multimodal prophylaxis in the prevention of nausea and vomiting following extended-release epidural morphine. Pain Prac 2010; 10(3): 245–248. 3. Kakuta N, Tsutsumi YM, Horikawa YT, et al. Neurokinin-1 receptor antagonism, aprepitant, effectively diminishes post-operative nausea and vomiting while increasing analgesic tolerance in laparoscopic gynecological procedures. J Med Invest 2011; 58(3–4): 246–251. 4. Fahler J, Wall GC and Leman BI. Gastroparesis-associated refractory nausea treated with aprepitant. Ann Pharmacother 2012; 46(12): e38. 5. Chong K and Dhatariya K. A case of severe, refractory diabetic gastroparesis managed by prolonged use of aprepitant. Nat Rev Endocrinol 2009; 5(5): 285–288. 6. Ellershaw J, Peat S and Boys L. Assessing the effectiveness of the hospital palliative care team. Palliat Med 1995; 9: 145–152. 7. Palliativedrugs.com. Bulletin Board. Aprepitant in Palliative Care. www.palliativedrugs.com/bulletin-board.html (2007– 2010, accessed 3 October 2013).
Downloaded from pmj.sagepub.com at GEORGIAN COURT UNIV on April 12, 2015
542193 case-report2014
PMJ00Palliative MedicineLowery et al.
Corrigenda
Corrigenda
Palliative Medicine 2014, Vol. 28(8) 1071 © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0269216314542193 pmj.sagepub.com
The use of aprepitant in a case of refractory nausea and vomiting Lowery L, Andrew I, Gill S, et al. The use of aprepitant in a case of refractory nausea and vomiting. Palliat Med 2014; 28(7): 990–991. DOI: 10.1177/0269216314530180. The wrong version of this article was exported for typesetting and subsequently published. The correct version of this article is reproduced on the following pages and replaces that published. The authors and editorial manager apologise for the error and any confusion caused.
Case Report
The use of aprepitant in a case of refractory nausea and vomiting
Palliative Medicine 2014, Vol. 28(7) 990–991 © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0269216314530180 pmj.sagepub.com
Lucy Lowery, Inga Andrew, Sarah Gill and Mark Lee
Abstract Background: This case report describes a patient whose refractory nausea and vomiting significantly improved with the use of aprepitant, a neurokinin 1 receptor antagonist currently only licensed for short-term use in chemotherapy-induced nausea and vomiting. Case presentation: A patient with breast cancer and meningeal metastases had an 18-month history of nausea and vomiting refractory to a number of antiemetics commonly used in palliative care. The nausea and vomiting resolved after receiving two doses of the drug aprepitant. Case management and outcome: Maintenance antiemetic treatment with aprepitant was continued over a 9-month period with no recurrence of nausea and vomiting, and no observed side effects. Conclusions: Aprepitant has a potential role as an antiemetic for nausea and vomiting within the palliative care setting and may be helpful for refractory symptoms.
Keywords Aprepitant, neurokinin 1 receptor antagonist, nausea, vomiting, refractory
Background Nausea and vomiting (NV) are common symptoms encountered by the palliative care population affecting up to 70% of patients with advanced cancer.1 Despite large number of antiemetics currently available, NV can be refractory. Aprepitant is an antiemetic drug, first authorised for use in 2003,2 and its mechanism of action is as a potent neurokinin 1 (NK1) antagonist. NK1 receptors are found at multiple sites within the central nervous system, including both the chemoreceptor trigger zone and the vomiting centre. Both of these areas are located in the brainstem and are important locations in the NV pathway. Aprepitant is currently only licensed for short-term use, given for 3 days as part of a combination regime, in chemotherapy-induced nausea and vomiting (CINV). Current evidence shows aprepitant improves CINV significantly when given in addition to the standard antiemetic regime (5-hydroxytryptamine (5HT3) antagonist plus dexamethasone). The addition of aprepitant increased the number of patients who had no vomiting and required no breakthrough antiemetic medication from 54% to 72%.3 Evidence for the use of aprepitant as an antiemetic outside of CINV is limited. A small case control study showed improvement in post-operative nausea and vomiting (PONV) with aprepitant use compared to combination treatment (ondansetron, dexamethasone and additional
antiemetics) following orthopaedic surgery, in which epidural morphine was felt to be the main cause of NV.4 Aprepitant has shown further benefit in a separate case control study, when given as a one-off preoperative dose prior to gynaecological surgery and used as a single agent compared to no antiemetic treatment.5 PONV was improved from 63% to 43% 2 h after surgery and from 27% to 0% after 24 h. Two single case studies reported the use of aprepitant for NV related to gastroparesis. Both describe patients with severe refractory symptoms of NV who had complete resolution of vomiting after the first two doses of aprepitant. The drug was used for 2 and 4 months, and no side effects were reported.6,7 Due to a current lack of evidence, its potential role within a palliative care setting is not clear. We describe a case of its effective use in refractory NV in a patient with breast cancer with meningeal metastases. St Benedict’s Hospice and Specialist Palliative Care Centre, Sunderland, UK Corresponding author: Mark Lee, St Benedict’s Hospice, St Benedict’s Way, Ryhope, Sunderland SR2 0NY, UK. Email: [email protected]
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Case presentation A 27-year-old woman was diagnosed with invasive lobular breast carcinoma with local lymphadenopathy and underwent surgery followed by adjuvant chemoradiotherapy. Fifteen months after completing treatment, she was diagnosed with meningeal metastases on computed tomography scan after she presented with headaches and NV. She underwent further chemotherapy, and a ventriculoperitoneal (VP) shunt was inserted after magnetic resonance imaging (MRI) revealed obstructive hydrocephalus. The shunt was revised 1 year later when both headaches and nausea increased in severity, and this resulted in an improvement in these symptoms. A further MRI was arranged some months later following a generalised seizure and showed progressive meningeal disease but no evidence of recurrent hydrocephalus. Since her diagnosis of meningeal metastases, she had persistent symptoms of NV which continued for 18 months. Her NV improved with both her VP shunt insertion and revision but never resolved completely. Similarly, her symptoms persisted despite treatment with a variety of antiemetics, both individually and in combination (including cyclizine, haloperidol, levomepromazine, olanzapine, metoclopramide, domperidone and dexamethasone), and utilising both oral and subcutaneous routes of administration. The most successful combination of antiemetics tried was subcutaneous olanzapine with dexamethasone, but despite reporting benefit from this regime, she still continued to have multiple episodes of NV daily. Another ‘broad spectrum’ regime tried combined cyclizine, levomepromazine and dexamethasone, but this failed to improve her symptoms at all. As a result of her persistent NV, she was admitted to an inpatient palliative care setting for a period of assessment and management. Due to the prolonged history and nature of her symptoms, it was felt that her NV may have an anticipatory element, but no improvement was seen with the addition of benzodiazepines or with psychological intervention. Furthermore, her NV failed to improve with empirical use of high-dose dexamethasone (up to 16 mg once daily) for presumed cerebral inflammation caused by her meningeal metastases. On examination, she had no signs of raised intracranial pressure (ICP), VP shunt blockage or meningism. Doses greater than 16 mg daily were not tried as she had already developed significant symptoms of Cushing’s syndrome. Due to exhaustion of all commonly used treatments and the persistence of her symptoms, the decision was made (after discussion with and consent from the patient) to try aprepitant.
Case management and outcome Aprepitant is an oral medication and is licensed to be given as a 3-day course in association with chemotherapy. Usual
practice is to give a loading dose of 120 mg followed by 2-day maintenance dose of 80 mg. It was anticipated that the drug would be used over a longer period, and as such a once daily dose of 80 mg was given. Daily Palliative Care Assessment Tool (PACA) scores8 were recorded to assess her symptoms of NV. PACA assesses symptom severity using a 4-point scale from 0 to 3. Before commencing aprepitant, she consistently scored her NV as a 2 or 3 (moderately affecting or dominating her day). After two doses of aprepitant, her PACA score reduced to 0 (symptom absent), and all other antiemetics (apart from dexamethasone) were withdrawn. Her symptoms of NV remained controlled for 9 months on treatment. The dose was increased with good effect (to 120 mg every third day) after 7 months when her NV recurred. She continued taking this higher dose of aprepitant for a further 2 months. The drug was stopped a few days before her death when she was no longer able to swallow. Overall, the use of aprepitant markedly improved her quality of life, and there were no definite or severe side effects noted with its longterm use. Common side effects such as hiccups, dyspepsia, constipation, headache, anorexia and fatigue2 were monitored by healthcare professionals as part of her holistic needs assessment.
Conclusion Aprepitant is an antiemetic currently not used routinely within the palliative care setting. This case demonstrates the effectiveness of aprepitant in a patient with refractory symptoms and though the precise mechanism for NV is not clear, it is most likely related to her meningeal metastases. On reviewing the literature, there appears to be only sparse use of this drug for NV outside of its CINV licence. There is no evidence of its use in NV secondary to raised ICP. The only use of aprepitant for refractory NV in a palliative care setting which was demonstrated in our search was located on the Palliativedrugs.com discussion board. Three single cases of its successful use for refractory NV in malignant disease were reported; however, an underlying cause for NV in these cases was not suggested.9 Interestingly in our case, and in previous case reports of refractory NV due to gastroparesis, the dramatic benefit of aprepitant has been seen after only 1–2 doses and has led to the withdrawal of multiple alternative medications and treatments in all three instances.6,7 This case study illustrates the potential of aprepitant as an effective antiemetic for refractory NV. Further research into its effectiveness in managing NV unrelated to chemotherapy, as well as data regarding its use long term, is essential. Acknowledgements The patient gave permission for this report to be published.
Declaration of conflicting interests The authors declare that there is no conflict of interest.
Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
References 1. Mannix K. Gastrointestinal symptoms. In:Hanks G, Cherny NL, Christakis NA, et al. (eds) Oxford textbook of palliative medicine. 4th ed. New York: Oxford University Press, 2010, p. 801. 2. Emend: summary of product characteristics. Electronic Medicines Compendium, http://www.medicines.org.uk/ emc/medicine/13868/SPC/EMEND++80mg%2c+125mg+ hard+Capsules/ (accessed 4 February 2014). 3. Dos Santos LV, Souza FH, Brunetto AT, et al. Neurokinin 1 receptor antagonists for chemotherapy induced nausea and vomiting: a systematic review. J Clin Oncol 2013; 31(15): 1280–1292.
Palliative Medicine 28(7) 4. Hartrick CT, Tang Y, Hunstad D, et al. Aprepitant vs. multimodal prophylaxis in the prevention of nausea and vomiting following extended-release epidural morphine. Pain Pract 2010; 10(3): 245–248. 5. Kakuta N, Tsutsumi YM, Horikawa YT, et al. Neurokinin-1 receptor antagonism, aprepitant, effectively diminishes post-operative nausea and vomiting while increasing analgesic tolerance in laparoscopic gynecological procedures. J Med Invest 2011; 58(3–4): 246–251. 6. Fahler J, Wall GC and Leman BI. Gastroparesis-associated refractory nausea treated with aprepitant. Ann Pharmacother 2012; 46(12): e38. 7. Chong K and Dhatariya K. A case of severe, refractory diabetic gastroparesis managed by prolonged use of aprepitant. Nat Rev Endocrinol 2009; 5(5): 285–288. 8. Ellershaw J, Peat S and Boys L. Assessing the effectiveness of the hospital palliative care team. Palliat Med 1995; 9: 145–152. 9. Aprepitant in palliative care, 2007–2010. Palliativedrugs. com, http://www.palliativedrugs.com/bulletin-board.html
PMJ0010.1177/0269216314530180Palliative MedicineLowery et al.
Case Report
The use of aprepitant in a case of refractory nausea and vomiting
Palliative Medicine 2014, Vol. 28(7) 990–991 © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0269216314530180 pmj.sagepub.com
Lucy Lowery, Inga Andrew, Sarah Gill and Mark Lee
Abstract Background: This case report describes a patient whose refractory nausea and vomiting significantly improved with the use of aprepitant, a neurokinin receptor antagonist currently only licensed for short-term use in chemotherapy-induced nausea and vomiting. Case presentation: A patient with breast cancer and meningeal metastases had an 18-month history of nausea and vomiting refractory to a number of antiemetics commonly used in palliative care. The nausea and vomiting resolved after receiving two doses of the drug aprepitant. Case management and outcome: Maintenance antiemetic treatment with aprepitant was continued over a 5-month period with no recurrence of nausea and vomiting, and no observed side effects. Conclusions: Aprepitant has a potential role as an antiemetic for refractory symptoms within the palliative-care setting. Keywords Aprepitant, neurokinin receptor antagonist, nausea, vomiting, refractory
Background Nausea and vomiting (NV) are common symptoms encountered by the palliative-care population, and are often very distressing for the patient. Despite the large number of antiemetics currently available in palliative care, NV can still be refractory in a small number of cases. Aprepitant is a relatively new antiemetic drug, and its mechanism of action is as a potent neurokinin (NK1) antagonist. NK1 receptors are found at multiple sites within the central nervous system, including both the chemoreceptor trigger zone and the vomiting centre. Both of these areas are located in the brainstem and are important locations in the NV pathway. Aprepitant is currently only licensed for short-term use in chemotherapy-induced NV (CINV). Current evidence shows that the addition of aprepitant to the standard antiemetic regime (5-hydroxytryptamine (5HT3) antagonist plus dexamethasone) improves symptoms of both acute and delayed phase CINV by around 18%.1 Evidence for the use of aprepitant as an antiemetic outside of CINV is limited. A small case control study showed improvement in post-operative NV (PONV) with aprepitant use compared to combination treatment (ondansetron, dexamethasone and additional antiemetics) following orthopaedic surgery, in which epidural morphine was felt to be the main cause of NV.2 Aprepitant has further shown to significantly improve PONV after gynaecological surgery when compared to no antiemetic treatment.3
Two single case studies reported the use of aprepitant for NV related to gastroparesis. Both describe patients with severe refractory symptoms of NV who showed a dramatic response to aprepitant within the first two doses. The drug was used for 2 and 4 months, and no side effects were reported.4,5 Due to a current lack of evidence, its potential role within a palliative-care setting is not clear. We describe a case of its effective use in refractory NV of uncertain aetiology in a patient with breast cancer with meningeal metastases.
Case presentation A 27-year-old female was diagnosed with invasive lobular breast carcinoma with local lymphadenopathy and underwent surgery followed by adjuvant chemoradiotherapy. A total of 15 months after completing this initial treatment, she was diagnosed with meningeal metastases on computed tomography scan after she presented with headaches and
St Benedict’s Hospice, Sunderland, UK Corresponding author: Mark Lee, St Benedict’s Hospice, St Benedict’s Way, Ryhope, Sunderland, SR2 0NY, UK. Email: [email protected]
Downloaded from pmj.sagepub.com at GEORGIAN COURT UNIV on April 12, 2015
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Lowery et al. NV. She underwent further chemotherapy, and a ventriculoperitoneal shunt was inserted after magnetic resonance imaging (MRI) revealed obstructive hydrocephalus. She subsequently had an 18-month history of NV which persisted despite treatment with a variety of antiemetics (cyclizine, haloperidol, levomepromazine, olanzapine, metoclopramide, domperidone, and dexamethasone inclusive), and utilising both oral and subcutaneous routes of administration. These had been tried systematically and based on careful consideration of the cause of the NV and the potential receptors involved. An MRI was arranged some months later following a generalised seizure and showed progressive meningeal disease but no evidence of recurrent hydrocephalus. As a result of her persistent NV, she was admitted to an inpatient palliative-care setting for a period of assessment. Due to the prolonged history of her symptoms, it was felt that her NV may have an anticipatory element, but no improvement was seen with the use of benzodiazepines or with psychological intervention. Furthermore, previous trials of high-dose dexamethasone (up to 16 mg once daily) failed to improve her NV. Due to exhaustion of all commonly used treatments and the persistence of her symptoms the decision was made (after discussion with the patient) to try aprepitant.
Case management and outcome Aprepitant is an oral medication and is licensed to be given as a 3-day course in association with chemotherapy. Usual practice is to give a loading dose of 120 mg followed by 2-day maintenance dose of 80 mg. It was anticipated that the drug would be used over a longer period and as such a once daily dose of 80 mg was given. Daily Palliative Care Assessment Tool (PACA) scores6 were recorded to assess her symptoms of NV. Before commencing aprepitant, she consistently scored her NV as a 2 or 3 (moderately affecting or dominating her day). After two doses of aprepitant, her PACA score reduced to 0 (symptom absent) and to date her symptoms of NV remain controlled after 5 months on treatment. Furthermore, over this time period her previous antiemetics have been withdrawn without any recurrence of NV. Overall, the use of aprepitant markedly improved her quality of life, and there were no definite or severe side effects noted with its long-term use. Common side effects such as hiccups, dyspepsia, constipation, headache, anorexia, and fatigue were monitored by health-care professionals as part of her holistic needs assessment.
Conclusion Aprepitant is a member of a relatively new class of antiemetic drugs, and as a result, it is not used routinely within the palliative-care setting. Although the precise mechanism for NV is not clear, this case demonstrates the
effectiveness of the drug in a patient with refractory symptoms. On reviewing the literature, there appears to be only sparse use of this drug for NV outside of its CINV licence. The only use of aprepitant for refractory NV in a palliativecare setting which was demonstrated in our search was located on the Palliativedrugs.com discussion board. Three single cases of its successful use for refractory NV in malignant disease were reported; however, an underlying cause for NV in these cases was not suggested.7 Interestingly, in our case and in previous case reports of refractory NV in patients with both malignancy and gastroparesis, the dramatic benefit of aprepitant has been seen after only 1–2 doses, and has regularly led to the withdrawal of multiple alternative medications and treatments.4,5 We believe that aprepitant could be an alternative antiemetic for patients with refractory NV who have demonstrated poor response to more traditional antiemetics used in palliative care. Further research into its effectiveness in managing NV unrelated to chemotherapy, as well as data regarding its use long term, would be beneficial. Acknowledgement The patient gave permission for this report to be published.
Declaration of conflicting interests The authors report no conflicts of interest.
Funding This report received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
References 1. Dos Santos LV, Souza FH, Brunetto AT, et al. Neurokinin-1 receptor antagonists for chemotherapy induced nausea and vomiting: a systematic review. J Clin Onc 2013; 31(15): 1280–1292. 2. Hartrick CT, Tang Y, Hunstad D, et al. Aprepitant vs. multimodal prophylaxis in the prevention of nausea and vomiting following extended-release epidural morphine. Pain Prac 2010; 10(3): 245–248. 3. Kakuta N, Tsutsumi YM, Horikawa YT, et al. Neurokinin-1 receptor antagonism, aprepitant, effectively diminishes post-operative nausea and vomiting while increasing analgesic tolerance in laparoscopic gynecological procedures. J Med Invest 2011; 58(3–4): 246–251. 4. Fahler J, Wall GC and Leman BI. Gastroparesis-associated refractory nausea treated with aprepitant. Ann Pharmacother 2012; 46(12): e38. 5. Chong K and Dhatariya K. A case of severe, refractory diabetic gastroparesis managed by prolonged use of aprepitant. Nat Rev Endocrinol 2009; 5(5): 285–288. 6. Ellershaw J, Peat S and Boys L. Assessing the effectiveness of the hospital palliative care team. Palliat Med 1995; 9: 145–152. 7. Palliativedrugs.com. Bulletin Board. Aprepitant in Palliative Care. www.palliativedrugs.com/bulletin-board.html (2007– 2010, accessed 3 October 2013).
Downloaded from pmj.sagepub.com at GEORGIAN COURT UNIV on April 12, 2015
542193 case-report2014
PMJ00Palliative MedicineLowery et al.
Corrigenda
Corrigenda
Palliative Medicine 2014, Vol. 28(8) 1071 © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0269216314542193 pmj.sagepub.com
The use of aprepitant in a case of refractory nausea and vomiting Lowery L, Andrew I, Gill S, et al. The use of aprepitant in a case of refractory nausea and vomiting. Palliat Med 2014; 28(7): 990–991. DOI: 10.1177/0269216314530180. The wrong version of this article was exported for typesetting and subsequently published. The correct version of this article is reproduced on the following pages and replaces that published. The authors and editorial manager apologise for the error and any confusion caused.
Case Report
The use of aprepitant in a case of refractory nausea and vomiting
Palliative Medicine 2014, Vol. 28(7) 990–991 © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0269216314530180 pmj.sagepub.com
Lucy Lowery, Inga Andrew, Sarah Gill and Mark Lee
Abstract Background: This case report describes a patient whose refractory nausea and vomiting significantly improved with the use of aprepitant, a neurokinin 1 receptor antagonist currently only licensed for short-term use in chemotherapy-induced nausea and vomiting. Case presentation: A patient with breast cancer and meningeal metastases had an 18-month history of nausea and vomiting refractory to a number of antiemetics commonly used in palliative care. The nausea and vomiting resolved after receiving two doses of the drug aprepitant. Case management and outcome: Maintenance antiemetic treatment with aprepitant was continued over a 9-month period with no recurrence of nausea and vomiting, and no observed side effects. Conclusions: Aprepitant has a potential role as an antiemetic for nausea and vomiting within the palliative care setting and may be helpful for refractory symptoms.
Keywords Aprepitant, neurokinin 1 receptor antagonist, nausea, vomiting, refractory
Background Nausea and vomiting (NV) are common symptoms encountered by the palliative care population affecting up to 70% of patients with advanced cancer.1 Despite large number of antiemetics currently available, NV can be refractory. Aprepitant is an antiemetic drug, first authorised for use in 2003,2 and its mechanism of action is as a potent neurokinin 1 (NK1) antagonist. NK1 receptors are found at multiple sites within the central nervous system, including both the chemoreceptor trigger zone and the vomiting centre. Both of these areas are located in the brainstem and are important locations in the NV pathway. Aprepitant is currently only licensed for short-term use, given for 3 days as part of a combination regime, in chemotherapy-induced nausea and vomiting (CINV). Current evidence shows aprepitant improves CINV significantly when given in addition to the standard antiemetic regime (5-hydroxytryptamine (5HT3) antagonist plus dexamethasone). The addition of aprepitant increased the number of patients who had no vomiting and required no breakthrough antiemetic medication from 54% to 72%.3 Evidence for the use of aprepitant as an antiemetic outside of CINV is limited. A small case control study showed improvement in post-operative nausea and vomiting (PONV) with aprepitant use compared to combination treatment (ondansetron, dexamethasone and additional
antiemetics) following orthopaedic surgery, in which epidural morphine was felt to be the main cause of NV.4 Aprepitant has shown further benefit in a separate case control study, when given as a one-off preoperative dose prior to gynaecological surgery and used as a single agent compared to no antiemetic treatment.5 PONV was improved from 63% to 43% 2 h after surgery and from 27% to 0% after 24 h. Two single case studies reported the use of aprepitant for NV related to gastroparesis. Both describe patients with severe refractory symptoms of NV who had complete resolution of vomiting after the first two doses of aprepitant. The drug was used for 2 and 4 months, and no side effects were reported.6,7 Due to a current lack of evidence, its potential role within a palliative care setting is not clear. We describe a case of its effective use in refractory NV in a patient with breast cancer with meningeal metastases. St Benedict’s Hospice and Specialist Palliative Care Centre, Sunderland, UK Corresponding author: Mark Lee, St Benedict’s Hospice, St Benedict’s Way, Ryhope, Sunderland SR2 0NY, UK. Email: [email protected]
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Lowery et al.
Case presentation A 27-year-old woman was diagnosed with invasive lobular breast carcinoma with local lymphadenopathy and underwent surgery followed by adjuvant chemoradiotherapy. Fifteen months after completing treatment, she was diagnosed with meningeal metastases on computed tomography scan after she presented with headaches and NV. She underwent further chemotherapy, and a ventriculoperitoneal (VP) shunt was inserted after magnetic resonance imaging (MRI) revealed obstructive hydrocephalus. The shunt was revised 1 year later when both headaches and nausea increased in severity, and this resulted in an improvement in these symptoms. A further MRI was arranged some months later following a generalised seizure and showed progressive meningeal disease but no evidence of recurrent hydrocephalus. Since her diagnosis of meningeal metastases, she had persistent symptoms of NV which continued for 18 months. Her NV improved with both her VP shunt insertion and revision but never resolved completely. Similarly, her symptoms persisted despite treatment with a variety of antiemetics, both individually and in combination (including cyclizine, haloperidol, levomepromazine, olanzapine, metoclopramide, domperidone and dexamethasone), and utilising both oral and subcutaneous routes of administration. The most successful combination of antiemetics tried was subcutaneous olanzapine with dexamethasone, but despite reporting benefit from this regime, she still continued to have multiple episodes of NV daily. Another ‘broad spectrum’ regime tried combined cyclizine, levomepromazine and dexamethasone, but this failed to improve her symptoms at all. As a result of her persistent NV, she was admitted to an inpatient palliative care setting for a period of assessment and management. Due to the prolonged history and nature of her symptoms, it was felt that her NV may have an anticipatory element, but no improvement was seen with the addition of benzodiazepines or with psychological intervention. Furthermore, her NV failed to improve with empirical use of high-dose dexamethasone (up to 16 mg once daily) for presumed cerebral inflammation caused by her meningeal metastases. On examination, she had no signs of raised intracranial pressure (ICP), VP shunt blockage or meningism. Doses greater than 16 mg daily were not tried as she had already developed significant symptoms of Cushing’s syndrome. Due to exhaustion of all commonly used treatments and the persistence of her symptoms, the decision was made (after discussion with and consent from the patient) to try aprepitant.
Case management and outcome Aprepitant is an oral medication and is licensed to be given as a 3-day course in association with chemotherapy. Usual
practice is to give a loading dose of 120 mg followed by 2-day maintenance dose of 80 mg. It was anticipated that the drug would be used over a longer period, and as such a once daily dose of 80 mg was given. Daily Palliative Care Assessment Tool (PACA) scores8 were recorded to assess her symptoms of NV. PACA assesses symptom severity using a 4-point scale from 0 to 3. Before commencing aprepitant, she consistently scored her NV as a 2 or 3 (moderately affecting or dominating her day). After two doses of aprepitant, her PACA score reduced to 0 (symptom absent), and all other antiemetics (apart from dexamethasone) were withdrawn. Her symptoms of NV remained controlled for 9 months on treatment. The dose was increased with good effect (to 120 mg every third day) after 7 months when her NV recurred. She continued taking this higher dose of aprepitant for a further 2 months. The drug was stopped a few days before her death when she was no longer able to swallow. Overall, the use of aprepitant markedly improved her quality of life, and there were no definite or severe side effects noted with its longterm use. Common side effects such as hiccups, dyspepsia, constipation, headache, anorexia and fatigue2 were monitored by healthcare professionals as part of her holistic needs assessment.
Conclusion Aprepitant is an antiemetic currently not used routinely within the palliative care setting. This case demonstrates the effectiveness of aprepitant in a patient with refractory symptoms and though the precise mechanism for NV is not clear, it is most likely related to her meningeal metastases. On reviewing the literature, there appears to be only sparse use of this drug for NV outside of its CINV licence. There is no evidence of its use in NV secondary to raised ICP. The only use of aprepitant for refractory NV in a palliative care setting which was demonstrated in our search was located on the Palliativedrugs.com discussion board. Three single cases of its successful use for refractory NV in malignant disease were reported; however, an underlying cause for NV in these cases was not suggested.9 Interestingly in our case, and in previous case reports of refractory NV due to gastroparesis, the dramatic benefit of aprepitant has been seen after only 1–2 doses and has led to the withdrawal of multiple alternative medications and treatments in all three instances.6,7 This case study illustrates the potential of aprepitant as an effective antiemetic for refractory NV. Further research into its effectiveness in managing NV unrelated to chemotherapy, as well as data regarding its use long term, is essential. Acknowledgements The patient gave permission for this report to be published.
Declaration of conflicting interests The authors declare that there is no conflict of interest.
Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
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