Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC.

Here we provide the updated version of the guidelines of the European Association for Palliative Care (EAPC) on the use of opioids for the treatment of cancer pain. The update was undertaken by the European Palliative Care Research Collaborative. Previous EAPC guidelines were reviewed and compared with other currently available guidelines, and consensus recommendations were created by formal international expert panel. The content of the guidelines was defined according to several topics, each of which was assigned to collaborators who developed systematic literature reviews with a common methodology. The recommendations were developed by a writing committee that combined the evidence derived from the systematic reviews with the panellists' evaluations in a co-authored process, and were endorsed by the EAPC Board of Directors. The guidelines are presented as a list of 16 evidence-based recommendations developed according to the Grading of Recommendations Assessment, Development and Evaluation system.

A systematic review of oxycodone in the management of cancer pain.

BACKGROUND: Oxycodone is often used as an opioid analgesic for moderate to severe cancer-related pain, but its use varies across Europe. This systematic literature review forms the basis of guidelines for oxycodone use within the European Palliative Care Research Collaborative opioid guidelines project conducted on behalf of the European Association for Palliative Care. OBJECTIVES: The objective of this study was to identify and assess the quality of evidence for the use of oxycodone for cancer pain in adults. METHODS: The Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, MedLine, EMBASE and CINAHL were systematically searched in addition to hand searching of relevant journals. Studies were included if they reported a clinical outcome relevant to the use of oxycodone in adult patients with moderate to severe cancer pain. Any form and route of oxycodone was included except intrathecal. No direct comparator was required for inclusion and studies were excluded if patients had previously switched from another strong opioid because of intolerable adverse effects or poor efficacy. This is a narrative systematic review, using the GRADE approach to assess the quality of studies and to formulate guidelines. RESULTS: Twenty-nine original studies were identified including a meta-analysis and 14 randomized controlled trials. The identified meta-analysis included three trials comparing oxycodone to morphine and one comparing oxycodone to hydromorphone. Four other randomized trials compared oxycodone with other opioids. The remaining randomized controlled trials compared different routes of administration or formulations of oxycodone. No additional studies that would have been suitable for addition to the meta-analysis were identified. CONCLUSIONS: There is no evidence from the included trials of a significant difference in analgesia or adverse effects between oxycodone and morphine or hydromorphone. The evidence was graded as high quality on the basis of a well-conducted meta-analysis, with no limitations likely to affect the outcome, in addition to consistency in the results of the other studies. The research was conducted using participants relevant to cancer and palliative care populations. Oxycodone can be recommended as an alternative to morphine or hydromorphone for cancer-related pain.

Studies comparing Numerical Rating Scales, Verbal Rating Scales, and Visual Analogue Scales for assessment of pain intensity in adults: a systematic literature review.

CONTEXT: The use of unidimensional pain scales such as the Numerical Rating Scale (NRS), Verbal Rating Scale (VRS), or Visual Analogue Scale (VAS) is recommended for assessment of pain intensity (PI). A literature review of studies specifically comparing the NRS, VRS, and/or VAS for unidimensional self-report of PI was performed as part of the work of the European Palliative Care Research Collaborative on pain assessment. OBJECTIVES: To investigate the use and performance of unidimensional pain scales, with specific emphasis on the NRSs. METHODS: A systematic search was performed, including citations through April 2010. All abstracts were evaluated by two persons according to specified criteria. RESULTS: Fifty-four of 239 papers were included. Postoperative PI was most frequently studied; six studies were in cancer. Eight versions of the NRS (NRS-6 to NRS-101) were used in 37 studies; a total of 41 NRSs were tested. Twenty-four different descriptors (15 for the NRSs) were used to anchor the extremes. When compared with the VAS and VRS, NRSs had better compliance in 15 of 19 studies reporting this, and were the recommended tool in 11 studies on the basis of higher compliance rates, better responsiveness and ease of use, and good applicability relative to VAS/VRS. Twenty-nine studies gave no preference. Many studies showed wide distributions of NRS scores within each category of the VRSs. Overall, NRS and VAS scores corresponded, with a few exceptions of systematically higher VAS scores. CONCLUSION: NRSs are applicable for unidimensional assessment of PI in most settings. Whether the variability in anchors and response options directly influences the numerical scores needs to be empirically tested. This will aid in the work toward a consensus-based, standardized measure.

The dimensionality of pain: palliative care and chronic pain patients differ in their reports of pain intensity and pain interference.

The accurate, precise, and consistent assessment of pain is of particular importance in palliative care. The European Palliative Care Research Collaborative is developing a computer-based pain assessment instrument and has been evaluating the content and dimensionality of existing pain questionnaires. The most important dimensions of pain are intensity and interference. However, since pain interference is a consequence of and largely reflects pain intensity, we postulated that it might either provide information to enhance the evaluation of intensity, or that an overall summary measure of pain severity could be constructed by combining the 2 dimensions. Cancer patients in palliative care (n=395) and chronic pain patients (n=168) completed questionnaires that included 23 pain items culled from existing questionnaires. Psychometric analyses confirmed the existence of 2 main dimensions, intensity and interference, and also guided identification of items that contributed most strongly to these dimensions. However, there was strong evidence that the relationship between the intensity and the interference items differs markedly in palliative care patients compared to chronic pain patients. As hypothesized, there was strong correlation between intensity and interference, lending support to the possibility that, for some purposes, these dimensions may be combined to provide a higher-level summary measure of patients' pain experience. We conclude that these dimensions should be kept distinct when assessing patients in general, although for a single type of patient (such as palliative care patients), it may be possible to regard intensity and interference as contributing to an overall measure of pain severity.

Sleep-wake disturbances in patients with advanced cancer and their family carers.

Sleep disturbance is common in patients with advanced cancer, and their family carers also may suffer from sleep problems. The aims of this study were to determine the prevalence of sleep-wake disturbances in patients with advanced cancer and their carers, to monitor the amount of daytime spent in activity and rest, and to examine the relationship between sleep, physical, and psychological symptoms. This was a prospective, descriptive observational study in patients with advanced incurable cancer and their carers attending a regional cancer center, using subjective (Short Form-36, Epworth Sleepiness Score, Hospital Anxiety and Depression Scale, Memorial Symptom Assessment Scale, and sleep history and diary) and objective (Actiwatch) assessments over a seven-day period. Sixty patients with advanced cancer and their family carers completed the study. Poor sleep was a frequent complaint: 47% of the patients and 42% of the carers reported that they did not sleep well, yet patients reported sleeping an average of 8.2 hours and carers 7.8 hours per night. The objective assessments revealed that although sleep efficiency (SE) was greater than 90% for most patients and carers, sleep fragmentation was high in both groups. Patients and carers who complained of poor sleep were significantly more anxious (P<0.001 and <0.05) compared with patients and carers who reported sleeping well. Patients who complained of poor sleep had significantly more pain (P<0.05). These results show that a substantial proportion of advanced cancer patients and their carers complained of poor sleep despite reporting "normal" duration of sleep. Objective measurements using Actiwatch revealed good SE but high levels of sleep fragmentation and movement, suggesting that sleep quality may be disturbed. Further work is required to investigate sleep quality and the consequences of poor sleep. In the meantime, health care professionals need to routinely inquire about sleep and consider possible reversible underlying factors, such as pain and anxiety, for those who report sleep disturbance.

Intensity and treatment of symptoms in 3,030 palliative care patients: a cross-sectional survey of the EAPC Research Network.

OBJECTIVE: This study aimed to describe intensity and treatment of symptoms other than pain in European palliative care units. PATIENTS: A total of 3,030 patients, including 2,064 that used an opioid, were included from 143 palliative care centers, in 21 European countries. RESULTS: Pain was treated with analgesics corresponding to the WHO pain ladder step I (n = 374), II (n = 497), and III (n = 1,567). Frequencies of symptoms observed as moderate or severe were for generalized weakness (50 percent), fatigue (48 percent), anxiety (28 percent), anorexia (26 percent), constipation (18 percent), focal weakness (18 percent), depression (18 percent), and dyspnoea (15 percent). When comparing WHO-groups, cancer diagnoses, metastasis sites, countries, and genders, we found that some of the symptom intensities and treatments differed significantly between subgroups. A majority of patients used drugs for symptom management. Still, more than one-third of patients assessed to have moderate or severe constipation did not receive any treatment. The corresponding numbers for depression, confusion, nausea, vomiting, or anxiety were approaching 40 percent and for poor sleep about 50 percent. Prescription practice of antiemetics, laxatives, and psychotropic drugs varied widely between countries both in terms of preparation and percent of patients receiving a specific treatment. CONCLUSIONS: This survey shows that clinically relevant symptoms are frequent and that one-third to half of the patients with a symptom observed as moderate or severe do not receive any treatment aimed to reduce the symptom intensity. Several symptoms and treatments differed between WHO-groups, cancer diagnoses, metastasis locations, countries, and genders. Prescription practice varied between countries both in terms of medication administered and percent of patients receiving specific treatment.

Patient demographics and centre description in European palliative care units.

Patients in palliative care are elderly, frail and in decline with multisystem disease. These and other factors make palliative care research particularly challenging, and has been one of several reasons why relatively little systematic research has been performed. The European Association for Palliative Care (EAPC) is seeking to emphasise the importance of research. The present project is the first empirical multicentre study organised by the EAPC Research Network, with the aim of identifying the patient population using specialised palliative care, and identifying a network of palliative care services across Europe, able to participate in a multicentre collaboration for research. During a designated week in the autumn of 2000, data on patients were recorded from 143 centres. The survey was carried out by means of two questionnaires, one centre questionnaire and one patient questionnaire. Data were submitted on 3013 patients from 22 different European countries. Almost all patients had cancer (94%), while some had neurological disease (3%). The majority (75%) had been referred to a palliative care service during the six to seven months before the survey was performed. Very few patients had less than one week of expected survival (6%), the majority were expected to live one to six months, while as many as 16% were expected to live more than one year. The majority of the patients (27%) were fully ambulatory--the ability to walk independently without any assistance. The majority of the patients (60%) received care as an outpatient, either at a traditional clinic in an outpatient cancer hospital (12%), in home-care programs from a specialised advisory service (24%), or external nursing care (24%). The population of patients included in this survey was not a sample of dying patients. There were a substantial number of patients with an anticipated life expectancy of more than six months. The study demonstrated a considerable enthusiasm for research in the palliative care community across Europe. The heterogeneity of the sample is evident, and this will need careful consideration for future clinical trials. This calls for an international consensus on how to report on patient characteristics within palliative care research. This is necessary in order to be able to evaluate the representativity of the study population, as well as to compare data between studies. The range of services encountered in the survey highlights the need for the organisational and clinical standards for palliative care, which can be audited.

Oxycodone for cancer-related pain: meta-analysis of randomized controlled trials.

To evaluate the efficacy and tolerability of oxycodone in cancer-related pain, we conducted a systematic review of randomized controlled trials. Four studies, comparing oral oxycodone with either oral morphine (n = 3) or oral hydromorphone (n = 1), were suitable for meta-analysis. Standardized mean differences in pain scores comparing oxycodone with control groups were pooled using random-effects models. Overall, there was no evidence that mean pain scores differed between oxycodone and control drugs (pooled standardized mean difference, 0.04; 95% confidence interval [CI], -0.29 to 0.36; P = .8; I(2) = 62%). In meta-regression analyses, pain scores were higher for oxycodone compared with morphine (0.20; 95% CI, -0.04 to 0.44) and lower compared with hydromorphone (-0.36; 95% CI, -0.71 to 0.00), although these effect sizes were small. The efficacy and tolerability of oxycodone are similar to morphine, supporting its use as an opioid for cancer-related pain.

Pain and pain treatments in European palliative care units. A cross sectional survey from the European Association for Palliative Care Research Network.

The Research Network of the European Association for Palliative Care (EAPC) performed a survey of 3030 cancer patients from 143 palliative care centres in 21 European countries. The survey addressed pain intensity and the use of non-opioid analgesics, adjuvant analgesics and opioids. Patients were treated with analgesics corresponding to the WHO pain ladder step I (n = 855), step II (n = 509) and step III (n = 1589). The investigators assessed 32% of the patients as having moderate or severe pain. In general there were small differences between pain intensities across different countries. Cancer primary sites and the presence of metastasis had only minor influences on pain intensity. The most frequently used non-opioid analgesics were NSAIDs (26%) and paracetamol (23%). Adjuvant analgesics or co-analgesics used by >1% of the patients were corticosteroids (39%), tricylic antidepressants (11%), gabapentin (5%), bisphosphonates (4%), clonazepam (2%), carbamazepine (4%) and phenytoin (2%). The use of non-opioid analgesics and co-analgesics varied widely between countries. Opioids administered for mild to moderate pain were codeine (8%), tramadol (8%), dextropropoxyphene (5%) and dihydrocodeine (2%). Morphine was the most frequently used opioid for moderate to severe pain (oral normal release morphine: 21%; oral sustained-release morphine: 19%; i.v. or s.c. morphine: 10%). Other opioids for moderate to severe pain were transdermal fentanyl (14%), oxycodone (4%), methadone (2%), diamorphine (2%) and hydromorphone (1%). We observed large variations in the use of opioids across countries. Finally, we observed that only a minority of the patients who used morphine needed very high doses.

Prognostic factors in advanced cancer patients: evidence-based clinical recommendations--a study by the Steering Committee of the European Association for Palliative Care.

PURPOSE: To offer evidence-based clinical recommendations concerning prognosis in advanced cancer patients. METHODS: A Working Group of the Research Network of the European Association for Palliative Care identified clinically significant topics, reviewed the studies, and assigned the level of evidence. A formal meta-analysis was not feasible because of the heterogeneity of published studies and the lack of minimal standards in reporting results. A systematic electronic literature search within the main available medical literature databases was performed for each of the following four areas identified: clinical prediction of survival (CPS), biologic factors, clinical signs and symptoms and psychosocial variables, and prognostic scores. Only studies on patients with advanced cancer and survival < or = 90 days were included. RESULTS: A total of 38 studies were evaluated. Level A evidence-based recommendations of prognostic correlation could be formulated for CPS (albeit with a series of limitations of which clinicians must be aware) and prognostic scores. Recommendations on the use of other prognostic factors, such as performance status, symptoms associated with cancer anorexia-cachexia syndrome (weight loss, anorexia, dysphagia, and xerostomia), dyspnea, delirium, and some biologic factors (leukocytosis, lymphocytopenia, and C-reactive protein), reached level B. CONCLUSION: Prognostication of life expectancy is a significant clinical commitment for clinicians involved in oncology and palliative care. More accurate prognostication is feasible and can be achieved by combining clinical experience and evidence from the literature. Using and communicating prognostic information should be part of a multidisciplinary palliative care approach.