Management of cancer pain: ESMO Clinical Practice Guidelines
incidence of pain
According to the World Health Organization (WHO), the incidence of cancer was 12 667 470 new cases in 2008 and, based on projections, it will be >15 million in 2020 [1]. Consistent with this, a systematic review of the literature, which investigated the prevalence of pain in different disease stages and types of cancer during the period 1966–2005[2], showed no difference in pain prevalence between patients during anticancer treatment and those in an advanced or terminal phase of the disease. In particular, pain prevalence was 64% in patients with metastatic, advanced or terminal phases of the disease, 59% in patients on anticancer treatment and 33% in patients after curative treatment. Moreover, in the systematic review of the literature carried out by Deandrea et al. [3] on studies published from 1994 to 2007, nearly half of the cancer patients were undertreated, with a high variability across study designs and clinical settings. Recent studies conducted both in Italy and in Europe [4, 5] confirmed these data, showing that pain was present in all phases of cancer disease (early and metastatic) and was not adequately treated in a significant percentage of patients, ranging from 56 to 82.3%. In particular, Apolone et al. [6] evaluated prospectively the adequacy of analgesic care of cancer patients by means of the Pain Management Index (PMI) in 1802 valid cases of in- and outpatients with advanced/metastatic solid tumor enrolled in 110 centers specifically devoted to cancer and/or pain management (oncology/pain/palliative centers or hospices). The study showed that patients were still classified as potentially undertreated in 25.3% of the cases (range 9.8–55.3%). In contrast to the percentage of incidence of pain reported in hematological patients (5% with leukemia and 38% with lymphoma) in the past literature [7], a significant proportion of patients with lymphoma and leukemia may suffer from pain not only in the last months of life (83%) [4] but also at the time of diagnosis and during active therapies [8]. Based on these facts it is evident that millions of cancer patients still suffer from cancer-related pain.
recommendation.
The assessment and management of pain in cancer patients is of paramount importance in all stages of the disease; however, pain is still not adequately treated (expert and panel consensus).
assessment of patients with pain
According to the literature, most patients with advanced cancer have at least two types of cancer-related pain which derive from a variety of etiologies [9, 10]. Sixty-nine per cent of patients rate their worst pain at a level that impaired their ability to function [11]. Table 1 shows the guidelines for a correct and complete assessment of the patient with pain. The proper and regular self-reporting assessment of pain with the help of validated assessment tools is the first step for an effective and individualized treatment. The most frequently used standardized scales [12] are reported in Figure 1 and are: visual analog scales (VAS), a verbal rating scale (VRS) and a numerical rating scale (NRS).
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Table 1.
Guidelines for a correct assessment of the patient with pain
Figure 1.
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Figure 1.
Validated and most frequently used pain assessment tools.
recommendation.
The intensity of pain and the treatment outcomes should be regularly assessed using (i) a visual analog scales (VAS), (ii) a verbal rating scale (VRS) or (iii) a numerical rating scale (NRS) [V, D].
Older age and the presence of limited communicative skills or of cognitive impairment such as during the last days of life makes the self-reporting of pain more difficult, although there is no evidence of clinical reductions in pain-related suffering. When cognitive deficits are severe, observation of pain-related behaviors and discomfort (i.e. facial expression, body movements, verbalization or vocalizations, changes in interpersonal interactions, changes in routine activity) is an alternative strategy for assessing the presence of pain (not its intensity) [13–16]. Different observational scales are available in the literature [15], but none of them is validated in different languages.
recommendation.
Observation of pain-related behaviors and discomfort is indicated in patients with cognitive impairment to assess the presence of pain (expert and panel consensus).
Psychosocial distress has to be assessed because it is strongly associated with cancer pain [17]. In fact psychosocial distress may amplify the perception of pain-related distress and, similarly, inadequately controlled pain may cause substantial psychological distress.
recommendation.
The assessment of all components of suffering such as psychosocial distress should be considered and evaluated [II, B].
principles of pain management
• Inform the patients about the possible onset of pain at any stage of the disease both during and after diagnostic interventions, in addition to as a consequence of cancer or anticancer treatments, and involve them in pain management. They have to be encouraged to communicate with the physician and/or the nurse about their suffering, the efficacy of therapy and any side effects, and not to consider the analgesic opioids as a therapeutic approach for dying patients [18], thus contributing to reduce opioidophobia. The patients’ involvement in pain management improves communication and has a beneficial effect on patients’ pain experience [19].
recommendation
Patients should be informed about pain and pain management and be encouraged to take an active role in their pain management [II, B].
• Prevent the onset of pain by means of the ‘by the clock’ administration, taking into account the half-life, bioavailability and duration of action of the different drugs.
recommendation
Analgesic for chronic pain should be prescribed on a regular basis and not on ‘as required’ schedule [V, D].
• Prescribe a therapy which is simple to be administered and easy to be managed by the patient himself and his family, especially when the patient is cared for at home. The oral route appears to be the most suitable to meet this requirement, and, if well tolerated, it must be considered as the preferred route of administration [20–24].
recommendation
The oral route of administration of the analgesic drugs should be advocated as the first choice [IV, C].
• Assess and treat the breakthrough pain (BTP) which is defined as a transitory exacerbation of pain that occurs in addition to an otherwise medically controlled stable pain [25, 26]. It is of sudden onset, occurs for short periods of time and is usually severe. The incidence of BTP has been estimated to be high (∼20–80% depending on the setting) in various surveys [26, 27]. The differences reported are probably due to the different clinical settings analyzed and the different definitions of BTP used.
recommendation
Rescue dose of medications (as required) other than the regular basal therapy must be prescribed for breakthrough pain episodes [V, D].
• Tailor the dosage, the type and the route of drugs administered according to each patient's needs. The type and the dose of the analgesic drugs is influenced by the intensity of pain (Table 2) and have to be promptly adjusted to reach a balance between pain relief and side effects. The rescue doses taken by the patients are an appropriate measure of the daily titration of the regular doses [25, 26]. An alternative route for opioid administration should be considered when oral administration is not possible because of severe vomiting, bowel obstruction, severe dysphagia or severe confusion, as well as in the presence of poor pain control, which requires rapid dose escalation, and/or in the presence of oral opioid-related adverse effects.
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Table 2.
Categorization of pain and appropriate analgesia
pain management
In 1986, the WHO proposed a strategy for cancer pain treatment based on a sequential three-step analgesic ladder from non-opioids to weak opioids to strong opioids according to pain intensity [28]. Twenty years after the first edition [20], the WHO cancer pain relief program remains the referral point for pain management. According to WHO guidelines, opioid analgesics are the mainstay of analgesic therapy and are classified according to their ability to control pain from mild to mild–moderate to moderate–severe intensity. Such pain intensity may be scored on an NRS as reported in Table 2 [24, 29, 30].
However, the intensity of pain is frequently reported as mild, moderate and severe and scored on an NRS respectively as ≤4, from 5 to 6, and ≥7 [31].
Opioid analgesics may be combined with non-opioid drugs such as paracetamol or with non-steroidal anti-inflammatory drugs (NSAIDs) and with adjuvant drugs. [32, 33].
recommendation
The analgesic treatment should start with drugs indicated by the WHO analgesic ladder appropriate for the severity of pain [II, B].
Pain should already be managed during the diagnostic evaluation. Most cancer patients can attain satisfactory relief of pain through an approach that incorporates primary antitumor treatments, systemic analgesic therapy and other non-invasive techniques such as psychological or rehabilitative interventions.
treatment of mild pain
For the treatment of mild pain non-opioid analgesics such as acetaminophen/paracetamol or an NSAID are widely used (Table 3).
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Table 3.
Selected non-opioid analgesics for mild pain (WHO step I)
NSAIDs are superior to placebo in relieving cancer pain in single dose studies. There is no evidence to support superior safety or efficacy of one NSAID over any other [34]. In a randomized clinical trial (RCT) carried out in a small sample of cancer patien
การจัดการอาการปวดของโรคมะเร็ง: ESMO แนวปฏิบัติทางคลินิกอุบัติการณ์ของอาการปวดAccording to the World Health Organization (WHO), the incidence of cancer was 12 667 470 new cases in 2008 and, based on projections, it will be >15 million in 2020 [1]. Consistent with this, a systematic review of the literature, which investigated the prevalence of pain in different disease stages and types of cancer during the period 1966–2005[2], showed no difference in pain prevalence between patients during anticancer treatment and those in an advanced or terminal phase of the disease. In particular, pain prevalence was 64% in patients with metastatic, advanced or terminal phases of the disease, 59% in patients on anticancer treatment and 33% in patients after curative treatment. Moreover, in the systematic review of the literature carried out by Deandrea et al. [3] on studies published from 1994 to 2007, nearly half of the cancer patients were undertreated, with a high variability across study designs and clinical settings. Recent studies conducted both in Italy and in Europe [4, 5] confirmed these data, showing that pain was present in all phases of cancer disease (early and metastatic) and was not adequately treated in a significant percentage of patients, ranging from 56 to 82.3%. In particular, Apolone et al. [6] evaluated prospectively the adequacy of analgesic care of cancer patients by means of the Pain Management Index (PMI) in 1802 valid cases of in- and outpatients with advanced/metastatic solid tumor enrolled in 110 centers specifically devoted to cancer and/or pain management (oncology/pain/palliative centers or hospices). The study showed that patients were still classified as potentially undertreated in 25.3% of the cases (range 9.8–55.3%). In contrast to the percentage of incidence of pain reported in hematological patients (5% with leukemia and 38% with lymphoma) in the past literature [7], a significant proportion of patients with lymphoma and leukemia may suffer from pain not only in the last months of life (83%) [4] but also at the time of diagnosis and during active therapies [8]. Based on these facts it is evident that millions of cancer patients still suffer from cancer-related pain.recommendation.The assessment and management of pain in cancer patients is of paramount importance in all stages of the disease; however, pain is still not adequately treated (expert and panel consensus).assessment of patients with painAccording to the literature, most patients with advanced cancer have at least two types of cancer-related pain which derive from a variety of etiologies [9, 10]. Sixty-nine per cent of patients rate their worst pain at a level that impaired their ability to function [11]. Table 1 shows the guidelines for a correct and complete assessment of the patient with pain. The proper and regular self-reporting assessment of pain with the help of validated assessment tools is the first step for an effective and individualized treatment. The most frequently used standardized scales [12] are reported in Figure 1 and are: visual analog scales (VAS), a verbal rating scale (VRS) and a numerical rating scale (NRS).View this table:In this windowIn a new windowTable 1.Guidelines for a correct assessment of the patient with painFigure 1.View larger version:In this windowIn a new windowDownload as PowerPoint SlideFigure 1.Validated and most frequently used pain assessment tools.recommendation.The intensity of pain and the treatment outcomes should be regularly assessed using (i) a visual analog scales (VAS), (ii) a verbal rating scale (VRS) or (iii) a numerical rating scale (NRS) [V, D].Older age and the presence of limited communicative skills or of cognitive impairment such as during the last days of life makes the self-reporting of pain more difficult, although there is no evidence of clinical reductions in pain-related suffering. When cognitive deficits are severe, observation of pain-related behaviors and discomfort (i.e. facial expression, body movements, verbalization or vocalizations, changes in interpersonal interactions, changes in routine activity) is an alternative strategy for assessing the presence of pain (not its intensity) [13–16]. Different observational scales are available in the literature [15], but none of them is validated in different languages.recommendation.Observation of pain-related behaviors and discomfort is indicated in patients with cognitive impairment to assess the presence of pain (expert and panel consensus).Psychosocial distress has to be assessed because it is strongly associated with cancer pain [17]. In fact psychosocial distress may amplify the perception of pain-related distress and, similarly, inadequately controlled pain may cause substantial psychological distress.recommendation.The assessment of all components of suffering such as psychosocial distress should be considered and evaluated [II, B].principles of pain management• Inform the patients about the possible onset of pain at any stage of the disease both during and after diagnostic interventions, in addition to as a consequence of cancer or anticancer treatments, and involve them in pain management. They have to be encouraged to communicate with the physician and/or the nurse about their suffering, the efficacy of therapy and any side effects, and not to consider the analgesic opioids as a therapeutic approach for dying patients [18], thus contributing to reduce opioidophobia. The patients’ involvement in pain management improves communication and has a beneficial effect on patients’ pain experience [19].recommendationPatients should be informed about pain and pain management and be encouraged to take an active role in their pain management [II, B].• Prevent the onset of pain by means of the ‘by the clock’ administration, taking into account the half-life, bioavailability and duration of action of the different drugs.recommendationAnalgesic for chronic pain should be prescribed on a regular basis and not on ‘as required’ schedule [V, D].• Prescribe a therapy which is simple to be administered and easy to be managed by the patient himself and his family, especially when the patient is cared for at home. The oral route appears to be the most suitable to meet this requirement, and, if well tolerated, it must be considered as the preferred route of administration [20–24].recommendationThe oral route of administration of the analgesic drugs should be advocated as the first choice [IV, C].• Assess and treat the breakthrough pain (BTP) which is defined as a transitory exacerbation of pain that occurs in addition to an otherwise medically controlled stable pain [25, 26]. It is of sudden onset, occurs for short periods of time and is usually severe. The incidence of BTP has been estimated to be high (∼20–80% depending on the setting) in various surveys [26, 27]. The differences reported are probably due to the different clinical settings analyzed and the different definitions of BTP used.recommendationRescue dose of medications (as required) other than the regular basal therapy must be prescribed for breakthrough pain episodes [V, D].• Tailor the dosage, the type and the route of drugs administered according to each patient's needs. The type and the dose of the analgesic drugs is influenced by the intensity of pain (Table 2) and have to be promptly adjusted to reach a balance between pain relief and side effects. The rescue doses taken by the patients are an appropriate measure of the daily titration of the regular doses [25, 26]. An alternative route for opioid administration should be considered when oral administration is not possible because of severe vomiting, bowel obstruction, severe dysphagia or severe confusion, as well as in the presence of poor pain control, which requires rapid dose escalation, and/or in the presence of oral opioid-related adverse effects.View this table:
In this window
In a new window
Table 2.
Categorization of pain and appropriate analgesia
pain management
In 1986, the WHO proposed a strategy for cancer pain treatment based on a sequential three-step analgesic ladder from non-opioids to weak opioids to strong opioids according to pain intensity [28]. Twenty years after the first edition [20], the WHO cancer pain relief program remains the referral point for pain management. According to WHO guidelines, opioid analgesics are the mainstay of analgesic therapy and are classified according to their ability to control pain from mild to mild–moderate to moderate–severe intensity. Such pain intensity may be scored on an NRS as reported in Table 2 [24, 29, 30].
However, the intensity of pain is frequently reported as mild, moderate and severe and scored on an NRS respectively as ≤4, from 5 to 6, and ≥7 [31].
Opioid analgesics may be combined with non-opioid drugs such as paracetamol or with non-steroidal anti-inflammatory drugs (NSAIDs) and with adjuvant drugs. [32, 33].
recommendation
The analgesic treatment should start with drugs indicated by the WHO analgesic ladder appropriate for the severity of pain [II, B].
Pain should already be managed during the diagnostic evaluation. Most cancer patients can attain satisfactory relief of pain through an approach that incorporates primary antitumor treatments, systemic analgesic therapy and other non-invasive techniques such as psychological or rehabilitative interventions.
treatment of mild pain
For the treatment of mild pain non-opioid analgesics such as acetaminophen/paracetamol or an NSAID are widely used (Table 3).
View this table:
In this window
In a new window
Table 3.
Selected non-opioid analgesics for mild pain (WHO step I)
NSAIDs are superior to placebo in relieving cancer pain in single dose studies. There is no evidence to support superior safety or efficacy of one NSAID over any other [34]. In a randomized clinical trial (RCT) carried out in a small sample of cancer patien
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