Good symptom management in oncology is associated with improved patient and family quality of life, greater treatment compliance, and may even offer survival advantages. With population growth and aging, the proportion of patients with multiple symptoms-both related and unrelated to their cancer-is anticipated to increase, supporting calls for a more routine and integrated approach to symptom management. This article presents a summary of the literature for the use of symptom assessment tools and reviews the management of four common and distressing symptoms commonly experienced by people with advanced cancer: pain, breathlessness, nausea and vomiting, and fatigue. We also discuss the role of palliative care in supporting a holistic approach to symptom management throughout the cancer trajectory.
PURPOSE OF REVIEW: This review was undertaken to survey recent literature for research reports and comprehensive clinical reviews addressing the pharmacologic management of nausea and vomiting (N&V) in advanced cancer. The goal was to integrate findings in a comprehensive article that incorporates palliative care concepts into antiemetic treatment.
RECENT FINDINGS: There are few published studies of N&V in advanced cancer; such research may be limited by the multicausal nature of N&V and participant burden to patients with life-limiting disease. Most articles are written by oncologists who also specialize in palliative care, and those addressing adverse effects of drugs used as antiemetics are found in other literature. Articles addressing more novel therapies, like cannabinoids and medical marijuana, are uncommon in the oncology literature. N&V in patients with progressive or advanced cancer is often multicausal. Nausea is more common and persistent, and even mild nausea is bothersome and may cause anxiety or depression. The mechanisms of nausea and vomiting overlap, but different neural pathways constitute the final pathway for each-the brainstem for vomiting and higher brain regions for nausea. Common causes of N&V in advanced cancer include constipation, opioids, and malignant bowel obstruction. About 40% have undetermined causes and may be exacerbated by impaired gastric emptying, chemical imbalances, or other factors. Several drugs that have antiemetic effects and act at different receptors are used to palliate N&V. There is a paucity of research that supports palliative antiemetic choices, and other research is needed to define potential therapeutic strategies that capitalize on differences between nausea and vomiting.
BACKGROUND: Bleeding occurs with some regularity at the end of life. Patients often endure fatigue, weakness, pain, dyspnea and anxiety. These symptoms are magnified in visually apparent bleeds. Management can be particularly challenging as we attempt to balance therapies with goals of care. Children are at risk for such complications and symptoms; providers must ensure comfort for both the patient and family.
CASE DESCRIPTION: A 7-year-old male with recurrent, refractory Burkitt lymphoma was frequently hospitalized for palliative chemotherapy and disease complications. On his final admission, he experienced gross hemoptysis and hematemesis: he was short of breath, fatigued and anxious due to his blood loss. His and his family's angst were heightened by "seeing" his bleed. Potential, especially invasive, treatments were limited by our goals to promote comfort, limit interventions, maintain alertness, poor intravenous access and a small bowel obstruction. Nebulized vasopressin, 10 units in 4ml of normal saline given over 10 minutes provided JC with needed relief. His bleeding remitted and he tolerated its administration.
CONCLUSION: There are many treatments for hemorrhage; however, given the challenges of goals of care, administration, side-effects and tolerability, further investigation into nebulized vasopressin as a potential therapy for hemoptysis and hematemesis at the end-of-life is warranted.
BACKGROUND: Bone metastases in the lower spine and pelvis are effectively palliated with radiotherapy (RT), though this can come with side effects such as radiation induced nausea and vomiting (RINV). We hypothesize that high rates of RINV occur in part because of the widespread use of inexpensive simple unplanned palliative radiotherapy (SUPR), over more complex and resource intensive 3D conformal RT, such as volumetric modulated arc therapy (VMAT).
METHODS: This is a randomized, multi-centre phase III trial of SUPR versus VMAT. We will accrue 250 patients to assess the difference in patient-reported RINV. This study is powered to detect a difference in quality of life between patients treated with VMAT vs. SUPR.
DISCUSSION: This trial will determine if VMAT reduces early toxicity compared to SUPR and may provide justification for this more resource-intensive and costly form of RT.
TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03694015 . Date of registration: October 3, 2018.
Background: This case report describes a patient with known idiopathic Parkinson’s disease, being managed with transdermal rotigotine, whose refractory nausea and vomiting was successfully controlled with subcutaneous levomepromazine. No drug-induced extrapyramidal side effects emerged.
Case presentation: A patient was found to have a locally advanced serous carcinoma, causing secondary bowel obstruction. Furthermore, due to compromised oral access, the patient’s oral antiparkinsonian medications for motor control were converted to transdermal rotigotine. Unfortunately, the patient’s nausea and vomiting was refractory to a number of recommended antiemetic options.
Case management: Low dose levomepromazine was administered on a, ‘when required’ basis, via subcutaneous injection.
Case outcome: After the first dose of levomepromazine, the patient’s nausea and vomiting completely subsided and no extrapyramidal side effects were observed. This was confirmed by daily assessments, revealing no worsening of the motor symptoms associated with idiopathic Parkinson’s disease.
Conclusions: The pharmacology of rotigotine and levomepromazine appear complementary and may allow for the simultaneous use of both drugs, with favourable outcomes. This case report highlights that rotigotine may afford protection against antipsychotic induced extrapyramidal side effects, while preserving antiemetic effects. Such combinations may have a role in the end-of-life management of idiopathic Parkinson’s disease.
Nausea and vomiting in palliative care are commonly experienced symptoms, and the aetiology is often multifactorial. The most common causes are impaired gastric emptying, chemical causes (eg medication) and visceral causes (eg constipation). Close attention should be paid to the clinical features which may suggest the likely cause. Antiemetic therapy should be guided by the likely aetiology, although in practice, the clinical picture is often complex, and so regular reassessment is essential for adequate symptom control.
A 14-year-old girl with a history of complex congenital heart disease in end-stage heart failure and with cyclic vomiting was admitted to our hospice program in 2012. Before hospice enrollment, she had required intermittent infusions of dexmedetomidine to abort cyclic vomiting episodes after cardiac catheterization procedures. Following a hospital admission in November 2013, she was discharged home in the care of our hospice on a continuous dexmedetomidine infusion. She remained on this infusion at varying doses (range of 0.1-0.38 mcg/kg/hour) for nearly three years, until her death in September 2016. This report describes the palliative use of dexmedetomidine in this patient and difficulties related to the use of this medication during the course of her care.
BACKGROUND: Gastrointestinal symptoms, including nausea, vomiting, bowel obstruction, ascites, constipation, and anorexia, are common and often refractory in advanced cancer patients. The palliation of gastrointestinal symptoms is important in improving the quality of life of cancer patients, as well as that of their families and caregivers. Currently published clinical guidelines for the management of gastrointestinal symptoms in cancer patients do not comprehensively cover the topics or are not based on a formal process for the development of clinical guidelines.
METHODS: The Japanese Society for Palliative Medicine (JSPM) developed comprehensive clinical guidelines for the management of gastrointestinal symptoms in cancer patients after a formal guideline development process.
RESULTS: This article summarizes the recommendations along with their rationale and a short summary of the development process of the JSPM gastrointestinal symptom management guidelines. We established 31 recommendations, all of which are based on the best available evidence and agreement of expert taskforce members.
DISCUSSION: Future clinical studies and continuous guideline updates are required to improve gastrointestinal symptom management in cancer patients.
BACKGROUND: Approved almost 15 years ago for use in the chemotherapy setting, palonosetron, a 2nd generation 5-hydroxtryptamine 3 receptor antagonist (5-HT3 RA), has demonstrated efficacy in preventing chemotherapy-induced nausea and vomiting. However, its utility in the prophylaxis and treatment of radiation-induced nausea and vomiting (RINV) has yet to be evaluated. In this pilot study, we investigated the rates of control in RINV in patients with pre-existing emesis.
METHODS: Patients with pre-existing emesis undergoing palliative radiotherapy to sites with emetic risk were prescribed palonosetron 0.5 mg before the start of radiation treatment, and every other day until completion of treatment. Patients were followed up in acute (day 1 of treatment to day 1 after treatment) and delayed phases (days 2-10 after treatment). Prophylaxis and rescue (PR) was defined as a decrease in anti-emetic use, or episodes of nausea and/or vomiting from baseline. Complete prophylaxis (CP) was defined as no increase in anti-emetic use, or episodes of nausea and/or vomiting. Secondary endpoints included control of nausea and quality of life (QOL), as assessed with the Functional Living Index-Emesis and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15 Palliative.
RESULTS: Fourteen patients were enrolled. Rates of control were higher in the acute phase (n=14) for nausea (PR =42.9%, CP =42.9%) and vomiting (PR =21.4%, CP =71.4%) compared to the delayed phase (n=13) for nausea (PR =42.9%, CP =7.7%) and vomiting (PR =15.4%, CP =53.8%).
CONCLUSIONS: Palonosetron appears to be safe and patients with pre-existing emesis receiving palliative radiotherapy. More studies are needed to investigate its efficacy in this patient population.
BACKGROUND: Nausea and vomiting are commonly experienced by cancer patients, and can be assessed by the Functional Life Index-Emesis (FLIE) instrument which employs a three-day recall period. However, it is unknown whether patients' responses to the FLIE better correlate with the average or the worst symptom severity of the recall period, or the severity of an individual day.
METHODS: Patients receiving emetogenic radiotherapy for painful bone metastases who were enrolled in one of three trials for anti-emetic medications (ondansetron, aprepitant/granisetron, or palonosetron) completed the FLIE at baseline, and days 3, 5, 7, or 10 during treatment and follow-up. The concordance correlation coefficient (rc) was calculated between FLIE overall nausea and vomiting and daily nausea, vomiting, and quality of life (QoL) using the average responses of the 3-day recall period and with each of the three days' responses.
RESULTS: Responses from eighty-nine patients who experienced nausea or vomiting were analysed. The highest concordance for FLIE nausea was with the 3-day average [during treatment: rc =0.698, 95% confidence interval (CI): 0.495, 0.829; follow-up: rc =0.821, 95% CI: 0.711, 0.892]. FLIE vomiting had the highest concordance with worst day vomiting (during treatment, rc =0.310, 95% CI: 0.194, 0.417) or two day-prior vomiting (follow-up, rc =0.902, 95% CI: 0.832, 0.944). FLIE nausea and vomiting had inconsistent concordances with daily assessments of QoL.
CONCLUSIONS: Responses to the FLIE questionnaire are most representative of average nausea severity. Larger cohorts to validate these findings are warranted to address the lack of power in this present study and to confirm the wording and justification of a three-day recall period for the FLIE.
BACKGROUND: Olanzapine as an antiemetic represents a new use of an antipsychotic drug. People with cancer may experience nausea and vomiting whilst receiving chemotherapy or radiotherapy, or whilst in the palliative phase of illness.
OBJECTIVES: To assess the efficacy and safety of olanzapine when used as an antiemetic in the prevention and treatment of nausea and vomiting related to cancer in adults.
SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase for published data on 20th September 2017, as well as ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform for unpublished trials. We checked reference lists, and contacted experts in the field and study authors.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) of olanzapine versus any comparator with or without adjunct therapies for the prevention or treatment, or both, of nausea or vomiting in people with cancer aged 18 years or older, in any setting, of any duration, with at least 10 participants per treatment arm.
DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. We used GRADE to assess quality of evidence for each main outcome. We extracted data for absence of nausea or vomiting and frequency of serious adverse events as primary outcomes. We extracted data for patient perception of treatment, other adverse events, somnolence and fatigue, attrition, nausea or vomiting severity, breakthrough nausea and vomiting, rescue antiemetic use, and nausea and vomiting as secondary outcomes at specified time points.
MAIN RESULTS: We included 14 RCTs (1917 participants) from high-, middle- and low-income countries, representing over 24 different cancers. Thirteen studies were in chemotherapy-induced nausea and vomiting. Oral olanzapine was administered during highly emetogenic (HEC) or moderately emetogenic (MEC) chemotherapy (12 studies); chemoradiotherapy (one study); or palliation (one study). Eight studies await classification and 13 are ongoing.The main comparison was olanzapine versus placebo/no treatment. Other comparisons were olanzapine versus NK1 antagonist, prokinetic, 5-HT3 antagonist or dexamethasone.We assessed all but one study as having one or more domains that were at high risk of bias. Eight RCTs with fewer than 50 participants per treatment arm, and 10 RCTs with issues related to blinding, were at high risk of bias. We downgraded GRADE assessments due to imprecision, inconsistency and study limitations. Olanzapine versus placebo/no treatment Primary outcomes Olanzapine probably doubles the likelihood of no nausea or vomiting during chemotherapy from 25% to 50% (risk ratio (RR) 1.98, 95% confidence interval (CI) 1.59 to 2.47; 561 participants; 3 studies; solid tumours; HEC or MEC therapy; moderate-quality evidence) when added to standard therapy. Number needed to treat for additional beneficial outcome (NNTB) was 5 (95% CI 3.3 - 6.6).It is uncertain if olanzapine increases the risk of serious adverse events (absolute risk difference 0.7% more, 95% CI 0.2 to 5.2) (RR 2.46, 95% CI 0.48 to 12.55; 7 studies, 889 participants, low-quality evidence).Secondary outcomes. Four studies reported patient perception of treatment. One study (48 participants) reported no difference in patient preference. Four reported quality of life but data were insufficient for meta-analysis. Olanzapine may increase other adverse events (RR 1.71, 95% CI 0.99 to 2.96; 332 participants; 4 studies; low-quality evidence) and probably increases somnolence and fatigue compared to no treatment or placebo (RR 2.33, 95% CI 1.30 to 4.18; anticipated absolute risk 8.2% more, 95% CI 1.9 to 18.8; 464 participants; 5 studies; moderate-quality evidence). Olanzapine probably does not affect all-cause attrition (RR 0.99, 95% CI 0.57 to 1.73; 943 participants; 8 studies; I² = 0%). We are uncertain if olanzapine increases attrition due to adverse events (RR 3.00, 95% CI 0.13 to 70.16; 422 participants; 6 studies). No participants withdrew due to lack of efficacy. We are uncertain if olanzapine reduces breakthrough nausea and vomiting (RR 0.38, 95% CI 0.10 to 1.47; 501 participants; 2 studies; I² = 54%) compared to placebo or no treatment. No studies reported 50% reduction in severity of nausea or vomiting, use of rescue antiemetics, or attrition.We are uncertain of olanzapine's efficacy in reducing acute nausea or vomiting. Olanzapine probably reduces delayed nausea (RR 1.71, 95% CI 1.40 to 2.09; 585 participants; 3 studies) and vomiting (RR 1.28, 95% CI 1.14 to 1.42; 702 participants; 5 studies).Subgroup analysis: 5 mg versus 10 mg. Planned subgroup analyses found that it is unclear if 5 mg is as effective an antiemetic as 10 mg. There is insufficient evidence to exclude the possibility that 5 mg may confer a lower risk of somnolence and fatigue than 10 mg.Other comparisons One study (20 participants) compared olanzapine versus NK1 antagonists. We observed no difference in any reported outcomes.One study (112 participants) compared olanzapine versus a prokinetic (metoclopramide), reporting that olanzapine may increase freedom from overall nausea (RR 2.95, 95% CI 1.73 to 5.02) and overall vomiting (RR 3.03, 95% CI 1.78 to 5.14). One study (62 participants) examined olanzapine versus 5-HT3 antagonists, reporting olanzapine may increase the likelihood of 50% or greater reduction in nausea or vomiting at 48 hours (RR 1.82, 95% CI 1.11 to 2.97) and 24 hours (RR 1.36, 95% CI 0.80 to 2.34). One study (229 participants) compared olanzapine versus dexamethasone, reporting that olanzapine may reduce overall nausea (RR 1.73, 95% CI 1.37 to 2.18), overall vomiting (RR 1.27, 95% CI 1.10 to 1.48), delayed nausea (RR 1.66, 95% CI 1.33 to 2.08) and delayed vomiting (RR 1.25, 95% CI 1.07 to 1.45).
AUTHORS' CONCLUSIONS: There is moderate-quality evidence that oral olanzapine probably increases the likelihood of not being nauseous or vomiting during chemotherapy from 25% to 50% in adults with solid tumours, in addition to standard therapy, compared to placebo or no treatment. There is uncertainty whether it increases serious adverse events. It may increase the likelihood of other adverse events, probably increasing somnolence and fatigue. There is uncertainty about relative benefits and harms of 5 mg versus 10 mg. We identified only RCTs describing oral administration. The findings of this review cannot be extrapolated to provide evidence about the efficacy and safety of any injectable form (intravenous, intramuscular or subcutaneous) of olanzapine.
BACKGROUND: Opioids are the foundation of treatment for cancer pain but can cause side-effects, one of the most common being nausea and vomiting, which can impair quality of life.
OBJECTIVE: To evaluate the evidence for the management of opioid-induced nausea and vomiting. This systematic review was undertaken as part of an update of the European Association for Palliative Care's opioid guidelines.
DESIGN: Searches of MEDLINE (1966-2017) and EMBASE (1980-2017) were done. Key eligibility criteria were: randomized controlled trials conducted in patients with cancer. The Grading of Recommendations Assessment Development and Evaluations system was applied to formulate recommendations.
RESULTS: Fifteen studies were eligible (1524 patients). The studies were grouped as follows: opioid switching (n = 8); the use of antiemetics to treat opioid-induced nausea and vomiting (n = 4); and change of route of administration of the opioid (n = 3). Three recommendations were formulated: A weak recommendation for switching from morphine to oxycodone in cancer patients with nausea (quality D); a weak recommendation for switching from tramadol to either codeine or hydrocodone for pain in cancer patients with nausea (quality D); and a weak recommendation for switching from morphine/oxycodone to methadone using the three-day switch method in patients with increasing pain considered untreatable with further opioid titration and/or with opioid-related side effects (quality C).
CONCLUSIONS: This systematic review can make only weak recommendations for the management of opioid-induced nausea and vomiting. There remains a need for high-quality studies before strong recommendations on the management of opioid-induced nausea and vomiting can be made.
The patients often present to palliative care with intractable nausea and vomiting. This may reduce the effectiveness of oral drugs and significantly affects the quality of life of these patients. Despite multiple drugs available for treatment, it is often difficult to control the symptoms. Olanzapine is an atypical antipsychotic and acts on multiple receptors and may help in treating vomiting in a patient with advanced malignancy. We report a case of gallbladder carcinoma who presented to us with intractable vomiting which was not relieved with a combination of traditional antiemetics but showed marked improvement with olanzapine.
BACKGROUND: The provision of pediatric palliative care in Asia Pacific varies between countries and availability of essential medications for symptoms at the end of life in this region is unclear.
OBJECTIVE: To determine medications available and used in the management of six symptoms at the end of life among pediatric palliative care practitioners in Asia Pacific. To identify alternative pharmacological strategies for these six symptoms if the oral route was no longer possible and injections are refused.
DESIGN AND SETTING: An online survey of all Asia Pacific Hospice Palliative Care Network (APHN) members was carried out to identify medications used for six symptoms (pain, dyspnea, excessive respiratory secretions, nausea/vomiting, restlessness, seizures) in dying children. Two scenarios were of interest: (1) hours to days before death and (2) when injectables were declined or refused.
RESULTS: There were 54 responses from 18 countries. Majority (63.0%) of respondents were hospital based. About half of all respondents were from specialist palliative care services and 55.6% were from high-income countries. All respondents had access to essential analgesics. Several perceived that there were no available drugs locally to treat the five other commonly encountered symptoms. There was a wide variation in preferred drugs for treating each symptom that went beyond differences in drug availability or formulations.
CONCLUSION: Future studies are needed to explore barriers to medication access and possible knowledge gaps among service providers in the region, so that advocacy and education endeavors by the APHN may be optimized.
Symptom management is an important part of both palliative care and end-of-life care. This article will examine the recent research evidence about drugs commonly used for symptom management in adult patients receiving palliative care. In particular, the management of symptoms where recent palliative care-based evidence has changed recommended practice will be reviewed. This includes: breathlessness, delirium, nausea and vomiting in bowel obstruction, opioid-induced constipation and upper respiratory tract secretions. For each symptom, a review of recent pharmacological evidence has been undertaken, with emphasis on potential important changes to physicians' practice.
The prevalence of nausea and vomiting in patients with advanced cancer varies, but it generally increases towards the end of life. Nausea and vomiting can be distressing and debilitating for patients, and can affect quality of life significantly. This article discusses the assessment of nausea and vomiting, current understanding of the emetic pathways, and pharmacological management of nausea and vomiting in patients with advanced cancer at the end of life.
L'ouvrage présente, dans une première partie, l'évolution naturelle de la maladie, les conséquences de la maladie sur les relations soignants - malade - famille. Puis des conseils pratiques sont proposés pour les patients et familles. Une dernière partie aborde l'accompagnement en soins palliatifs et les lois relatives à la fin de vie 2005 et 2016 notamment.
BACKGROUND: Haloperidol is widely prescribed as an antiemetic in patients receiving palliative care, but there is limited evidence to support and refine its use.
OBJECTIVE: To explore the immediate and short-term net clinical effects of haloperidol when treating nausea and/or vomiting in palliative care patients.
DESIGN: A prospective, multicenter, consecutive case series.
SETTING/SUBJECTS: Twenty-two sites, five countries: consultative, ambulatory, and inpatient services.
MEASUREMENTS: When haloperidol was started in routine care as an antiemetic, data were collected at three time points: baseline; 48 hours (benefits); day seven (harms). Clinical effects were assessed using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE).
RESULTS: Data were collected (May 2014–March 2016) from 150 patients: 61% male; 86% with cancer; mean age 72 (standard deviation 11) years and median Australian-modified Karnofsky Performance Scale 50 (range 10–90). At baseline, nausea was moderate (88; 62%) or severe (11; 8%); 145 patients reported vomiting, with a baseline NCI CTCAE vomiting score of 1.0. The median (range) dose of haloperidol was 1.5 mg/24 hours (0.5–5 mg/24 hours) given orally or parenterally. Five patients (3%) died before further data collection. At 48 hours, 114 patients (79%) had complete resolution of their nausea and vomiting, with greater benefit seen in the resolution of nausea than vomiting. At day seven, 37 (26%) patients had a total of 62 mild/moderate harms including constipation 25 (40%); dry mouth 13 (21%); and somnolence 12 (19%).
CONCLUSIONS: Haloperidol as an antiemetic provided rapid net clinical benefit with low-grade, short-term harms.
Nausea and vomiting are common in people with life-limiting diseases and those nearing the end of life. Edith Ubogagu examines the mechanisms that lead to these symptoms and reviews the evidence for the efficacy of various classes of drugs in alleviating them.