Management of cancer pain: ESMO Clinical Practice Guidelines
2011; Elsevier BV; Volume: 22; Linguagem: Inglês
10.1093/annonc/mdr390
ISSN1569-8041
AutoresCarla Ripamonti, Elena Bandieri, Fausto Roila,
Tópico(s)Oral health in cancer treatment
ResumoAccording 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.Frankish H. 15 million new cancer cases per year by 2020, says WHO.Lancet. 2003; 361: 1278Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar]. 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.Van den Beuken-van Everdingen M.H.J. De Rijke J.M. Kessels A.G. et al.Prevalence of pain in patients with cancer: a systematic review of the past 40 years.Ann Oncol. 2007; 18: 1437-1449Abstract Full Text Full Text PDF PubMed Scopus (1271) Google Scholar], 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.Deandrea S. Montanari M. Moja L. et al.Prevalence of undertreatment in cancer pain. A review of published literature.Ann Oncol. 2008; 19: 1985-1991Abstract Full Text Full Text PDF PubMed Scopus (644) Google Scholar] 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.Costantini M. Ripamonti C. Beccaro M. et al.Prevalence, distress, management and relief of pain during the last three months of cancer patients' life. Results of an Italian mortality follow-back survey.Ann Oncol. 2009; 20: 729-735Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar, 5.Breivik H. Cherny N. Collett F. et al.Cancer-related pain: a pan European survey of prevalence, treatment, and patient attitudes.Ann Oncol. 2009; 20: 1420-1433Abstract Full Text Full Text PDF PubMed Scopus (556) Google Scholar] 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.Apolone G. Corli O. Caraceni A. et al.Pattern and quality of care of cancer pain management. Results from the Cancer Pain Outcome Research Study Group.Br J Cancer. 2009; 100: 1566-1574Crossref PubMed Scopus (139) Google Scholar] 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.Foley K.M. The treatment of cancer pain.N Engl J Med. 1985; 313: 84-94Crossref PubMed Scopus (808) Google Scholar], a significant proportion of patients with lymphoma and leukemia may suffer from pain not only in the last months of life (83%) [4.Costantini M. Ripamonti C. Beccaro M. et al.Prevalence, distress, management and relief of pain during the last three months of cancer patients' life. Results of an Italian mortality follow-back survey.Ann Oncol. 2009; 20: 729-735Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar] but also at the time of diagnosis and during active therapies [8.Morselli M. Bandieri E. Zanin R. et al.Pain and emotional distress in leukaemia patients at diagnosis.Leuk Res. 2009; 34: e67-e68Crossref PubMed Scopus (25) Google Scholar]. Based on these facts it is evident that millions of cancer patients still suffer from cancer-related pain. 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). 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.Higginson I.J. Murtagh F. Bruera E. Portenoy R.K. Cancer pain epidemiology.Cancer Pain. Assessment and Management. Vol. 3. Cambridge University Press, Cambridge2010: 37-52Google Scholar, 10.Portenoy R.K. Koh M. Bruera E. Portenoy R.K. Cancer pain syndromes.Cancer Pain. Assessment and Management. Vol. 4. Cambridge University Press, Cambridge2010: 53-88Google Scholar]. Sixty-nine per cent of patients rate their worst pain at a level that impaired their ability to function [11.Larue F. Colleau S.M. Brasseur L. Cleeland C.S. Multicentre study of cancer pain and its treatment in France.BMJ. 1995; 310: 1034-1037Crossref PubMed Scopus (309) Google Scholar]. 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.Caraceni A. Cherny N. Fainsinger R. et al.The Steering Committee of the EAPC Research Network. Pain measurement tools and methods in clinical research in palliative care: recommendations of an expert working group of the European Association of Palliative Care.J Pain Symptom Manage. 2002; 23: 239-255Abstract Full Text Full Text PDF PubMed Scopus (356) Google Scholar] are reported in Figure 1 and are: visual analog scales (VAS), a verbal rating scale (VRS) and a numerical rating scale (NRS).Table 1Guidelines for a correct assessment of the patient with pain1. Assess and re-assess the pain• Causes, onset, type, site, duration, intensity, relief and temporal patterns of the pain• Presence of the trigger factors and the signs and symptoms associated with the pain• Use of analgesics and their efficacy and tolerability2. Assess and re-assess the patient• The clinical situation by means of a complete/specific physical examination and the specific radiological and/or biochemical investigations• The presence of interference of pain with the patient's daily activities, work, social life, sleep patterns, appetite, sexual functioning and mood• The impact of the disease and the therapy on the physical, psychological and social conditions• The presence of a caregiver, the psychological status, the degree of awareness of the disease, anxiety and depression and suicidal ideation, his/her social environment, quality of life, spiritual concerns/needs• The presence and intensity of signs, physical and/or emotional symptoms associated with cancer pain syndromes• The functional status• The presence of opiophobia3. Assess and re-assess your ability to inform and to communicate with the patient and the family• Take time to spend with the patient and the family to understand their needs Open table in a new tab 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.Kaasalainen S. Pain assessment in older adults with dementia using behavioural observation methods in clinical practice.J Gerontol Nurs. 2007; 33: 6-10Crossref PubMed Scopus (32) Google Scholar, 14.Gordon D.B. Dahl J.L. Miaskowski C. et al.American Pain Society recommendations for improving the quality of acute and cancer pain management: American Pain Society Quality of Care Task Force.Arch Intern Med. 2005; 165: 1574-1580Crossref PubMed Scopus (533) Google Scholar, 15.Van Herk R. van Dijk M. Baar F.P.M. Tibboel D. de Wit R. Observational scales for pain assessment in older adults with cognitive impairments or communication difficulties.Nurs Res. 2007; 56: 34-43Crossref PubMed Scopus (69) Google Scholar, 16.American Geriatrics Society Panel on Persistent Pain in Older Persons. The management of persistent pain in older persons.J Am Geriatr Soc. 2002; 50: S205-S224Crossref PubMed Google Scholar]. Different observational scales are available in the literature [15.Van Herk R. van Dijk M. Baar F.P.M. Tibboel D. de Wit R. Observational scales for pain assessment in older adults with cognitive impairments or communication difficulties.Nurs Res. 2007; 56: 34-43Crossref PubMed Scopus (69) Google Scholar], but none of them is validated in different languages. 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.Zaza C. Baine N. Cancer pain and psychosocial factors: a critical review of the literature.J Pain Symptom Manage. 2002; 24: 526-542Abstract Full Text Full Text PDF PubMed Scopus (261) Google Scholar]. In fact psychosocial distress may amplify the perception of pain-related distress and, similarly, inadequately controlled pain may cause substantial psychological distress. The assessment of all components of suffering such as psychosocial distress should be considered and evaluated [II, B]. • 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.Reid C.M. Gooberman Hill R. Hanks G.W. Opioid analgesics for cancer pain: symptom control for the living or comfort for the dying? A qualitative study to investigate the factors influencing the decision to accept morphine for pain caused by cancer.Ann Oncol. 2008; 19: 44-48Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar], thus contributing to reduce opioidophobia. The patients' involvement in pain management improves communication and has a beneficial effect on patients' pain experience [19.De Witr van Dam F. Zandbelt L. et al.A pain education program for chronic cancer pain patients: follow-up results from a randomized controlled trial.Pain. 1997; 73: 55-69Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar]. 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. 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.World Health Organization Cancer Pain Relief.2nd edn. World Health Organization, Geneva1996Google Scholar, 21.National Comprehensive Cancer Network (NCCN) Clinical Practice Guideline in Oncology.Adult Cancer Pain V.I. 2009; Google Scholar, 22.Hanks G.W. De Conno F. Ripamonti C. et al.Morphine in cancer pain: modes of administration.BMJ. 1996; 312: 823-826Crossref PubMed Scopus (12) Google Scholar, 23.Hanks G.W. De Conno F. Cherny N. et al.the Expert Working Group of the Research Network of the European Association for Palliative Care. Morphine and alternative opioids in cancer pain.Br J Cancer. 2001; 84: 587-593Crossref PubMed Scopus (794) Google Scholar, 24.Scottish Intercollegiate Guidelines Network Control of Pain in Adults with Cancer. A National Clinical Guideline. SIGN-Scottish Intercollegiate Guidelines Network. November 2008.Google Scholar]. 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.Portenoy R.K. Hagen N.A. Breakthrough pain: definition, prevalence, and characteristics.Pain. 1990; 41: 273-281Abstract Full Text PDF PubMed Scopus (802) Google Scholar, 26.Mercadante S. Radbruch L. Caraceni A. et al.Episodic (breakthrough) pain. Consensus Conference of an expert working group of the European Association for Palliative Care.Cancer. 2002; 94: 832-839Crossref PubMed Scopus (317) Google Scholar]. 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.Mercadante S. Radbruch L. Caraceni A. et al.Episodic (breakthrough) pain. Consensus Conference of an expert working group of the European Association for Palliative Care.Cancer. 2002; 94: 832-839Crossref PubMed Scopus (317) Google Scholar, 27.Bruera E. MacMillian K. Kuehn N. et al.Circadian distribution of extra doses of narcotic analgesics in patients with cancer pain: a preliminary report.Pain. 1992; 49: 311-314Abstract Full Text PDF PubMed Scopus (48) Google Scholar]. The differences reported are probably due to the different clinical settings analyzed and the different definitions of BTP used. 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.Portenoy R.K. Hagen N.A. Breakthrough pain: definition, prevalence, and characteristics.Pain. 1990; 41: 273-281Abstract Full Text PDF PubMed Scopus (802) Google Scholar, 26.Mercadante S. Radbruch L. Caraceni A. et al.Episodic (breakthrough) pain. Consensus Conference of an expert working group of the European Association for Palliative Care.Cancer. 2002; 94: 832-839Crossref PubMed Scopus (317) Google Scholar]. 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.Table 2Categorization of pain and appropriate analgesiaWHO analgesic ladder stepScore on NRSaScore on NRS according to references 24, 29, 30.Analgesics of choice1 (mild pain) 6 out of 10Strong opioids ± paracetamol NSAIDsNRS, numerical rating scale; NSAIDs, non-inflammatory drugs; WHO, World Health Organization.a Score on NRS according to references 24, 29, 30. Open table in a new tab NRS, numerical rating scale; NSAIDs, non-inflammatory drugs; WHO, World Health Organization. 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.World Health Organization Cancer Pain Relief. World Health Organization, Geneva1986Google Scholar]. Twenty years after the first edition [20.World Health Organization Cancer Pain Relief.2nd edn. World Health Organization, Geneva1996Google Scholar], 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.Scottish Intercollegiate Guidelines Network Control of Pain in Adults with Cancer. A National Clinical Guideline. SIGN-Scottish Intercollegiate Guidelines Network. November 2008.Google Scholar, 29.Wallenstein S. Heidrich Gr. Kaiko R. Houde R. Clinical evaluation of mild analgesics: the measurement of clinical pain.Br J Clin Pharmacol. 1980; 10: 319s-327sCrossref PubMed Scopus (106) Google Scholar, 30.Littman G. Walker B. Schneider B. Reassessment of verbal and visual analog ratings in analgesic studies.Clin Pharmacol Ther. 1985; 38: 16-23Crossref PubMed Scopus (145) Google Scholar]. 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.Serlin R.C. Mendoza T.R. Nakamura Y. Edwards K.R. Cleeland C.S. When is cancer pain mild, moderate or severe? Grading pain severity by its interference with function.Pain. 1995; 61: 277-284Abstract Full Text PDF PubMed Scopus (1163) Google Scholar]. 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.Lussier D. Portenoy R.K. Bruera E. Higginson I.J. Ripamonti C. von Gunten C. Adjuvant analgesic drugs.Textbook of palliative medicine. Edward Arnold Publishers, London2006: 402-414Google Scholar, 33.Ripamonti C. Bandieri E. Cancer pain.Crit Rev Oncol Hematol. 2009; 70: 145-149Crossref PubMed Scopus (48) Google Scholar]. 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. For the treatment of mild pain non-opioid analgesics such as acetaminophen/paracetamol or an NSAID are widely used (Table 3).Table 3Selected non-opioid analgesics for mild pain (WHO step I)SubstanceWidely available forms and strengthsTime to onset (min)CautionMaximal daily doseAcetaminophen (paracetamol)Tablets, suppositories 500–1000 mg15–30Hepatotoxicity4 × 1000 mgAcetylsalycic acidTablets 500–1000 mg15–30GI toxicity, allergy, platelet inhibition3 × 1000 mgIbuprofenTablets 200–400–600 mg; tablets 800 mg modified release; topical gels15–30; 120+GI and renal toxicity4 × 600 mg; 3× 800 mg modified releaseKetoprofenTablets 25–75 mg; tablets 100–150–200 mg modified release30+GI and renal toxicity4 × 75 mg; 2 × 200 mgDiclofenacTablets 25–50–75 mg; tablets 100 mg modified release30–120GI and renal toxicity4 × 50 mg; 2 × 100 mgMefenamic acidCapsules 250–500 mg30+GI and renal toxicity4 × 500 mgNaproxenTablets 250–375–500 mg30+GI and renal toxicity2 × 500 mgGI, gastrointestinal; WHO, World Health Organization. Open table in a new tab GI, gastrointestinal; WHO, World Health Organization. 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.McNicol E. Strassels S. Gouds L. Lau J. Carr D. NSAIDs or paracetamol, alone or combined with opioids, for cancer pain (Cochrane Review).Cochrane Database Syst Rev. 2009; 1 (CD005180)Google Scholar]. In a randomized clinical trial (RCT) carried out in a small sample of cancer patients on a strong opioid regimen, paracetamol improved pain and well-being [35.Stockler M. Vardy J. Pillai A. Warr D. Acetominophen (paracetamol) improves pain and well-being in people with advanced cancer already receiving a strong opioid regimen: a randomized, double-blind, placebo-controlled cross-over trial.J Clin Oncol. 2004; 22: 3389-3394Crossref PubMed Scopus (105) Google Scholar]. However, these results have not been confirmed by other studies. Paracetamol and/or a non-steroidal anti-inflammatory drug are effective for treating mild pain [I, A]. Paracetamol and NSAIDS are universally accepted as part of the treatment of cancer pain at any stage of the WHO analgesic ladder. The long-term use of NSAIDs or a cyclo-oxygenase-2 (COX-2) selective inhibitor has to be carefully monitored and reviewed periodically [36.Joint Formulary Committee British National Formulary.55th edn. British Medical Association and Royal Pharmaceutical Society of Great Britain, London2007Google Scholar] because they can provoke severe toxicity such as: gastrointestinal bleeding, platelet dysfunction and renal failure. COX-2 selective inhibitors may increase the risk of thrombotic cardiovascular adverse reactions [37.European Medicines Agency. Public statement: European Medicines Agency announces regulatory action on COX-2 inhibitors (EMEA/62838/2005). Available from http://www.emea.europa.eu/pdfs/human/press/pr/6275705en.pdf.Google Scholar] and do no protect from renal failure. Not all of the described drugs are available in all countries. Paracetamol and/or a non-steroidal anti-inflammatory drug are effective for treating all intensities of pain, at least in the short term and unless contraindicated [I, A]. Traditionally [20.World Health Organization Cancer Pain Relief.2nd edn. World Health Organization, Geneva1996Google Scholar], patients with mild–moderate pain have been treated with a combination product containing acetaminophen, aspirin or NSAID plus a weak immediate-release opioid such as codeine, dihydrocodeine, tramadol or propoxyphene (Table 4).Table 4Comparison of selected opioids for mild to moderate pain (WHO step II)SubstanceWidely available forms and strengthsRelative effectiveness compared with oral morphineDuration of effectiveness (h)Maximal daily doseStarting dose without pretreatmentDihydrocodeineModified-release tablets 60–90–120 mg0.1712240 mg60–120 mgCodeineTablet 15–30–60 mg4–6360 mg15–60 mgTramadolDrops 100 mg/ml; capsules 50 mg0.1–0.22–4400 mg50–100 mgModified-release tablets 100–150–200 mg0.1–0.212400 mg50–100 mgWHO, World Health Organization. Open table in a new tab WHO, World Health Organization. The use of drugs of the second step of the WHO ladder has several controversial aspects. The first criticism concerns the absence of a definitive proof of efficacy of weak opioids: in a meta-analysis of data reported from clinical RCTs [38.Eisenberg E. Berkey C. Carr D.B. Mosteller F. Chalmers C. Efficacy and safety of nonsteroidal antinflammatory drugs for cancer pain: a meta-analysis.J Clin Oncol. 1994; 12: 2756-2765Crossref PubMed Scopus (213) Google Scholar] no significant difference was found in the effectiveness between non-opioid analgesics alone, and the combination of these with weak opioids. The available studies do not even demonstrate a clear difference in the effectiveness of the drugs between the first and the second step [39.Agency for Healthcare Research and Quality Evidence Report/Technology Assessment: Number 35. 2001; Google Scholar]. Uncontrolled studies also show that the effectiveness of the second step of the WHO ladder has a time limit of 30–40 days for most patients and that the shift to the third step is mainly due to insufficient analgesia achieved, rather than to adverse effects [40.Ventafridda V. Tamburini M. Caraceni A. De Conno F. Naldi F. A validation study of the WHO method for cancer pain relief.Cancer. 1987; 59: 850-856Crossref PubMed Scopus (613) Google Scholar]. A further limitation in the use of weak opioids is represented by the 'ceiling effect', for which more than a certain threshold of dose cannot increase the effectiveness of the drug but only influence the appearance of side effects. Many authors have proposed the abolition of the second step of the WHO analgesic ladder, in favor of the early use of morphine at low doses. The few studies on this specific topic [41.Marinangeli F. Ciccozzi A. Leonardis M. et al.Use of strong opioids in advanced cancer pain: a randomized trial.J Pain Symptom Manage. 2004; 27: 409-416Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar, 42.Maltoni M. Scarpi E. Modonesi C. et al.A validation study of the WHO analgesic ladder: a two-step vs three-step strategy.Support Care Cancer. 2005; 13: 888-894Crossref PubMed Scopus (102) Google Scholar, 43.Mercadante S. Porzio G. Ferrera P. et al.Low morphine doses in opioid-naive cancer patients with pain.J Pain Symptom Manage. 2006; 31: 242-247Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar], though suggestive, have reported inconclusive results due both to the low number and representativeness of the patients sample studied and to the relatively low statistical power. An RCT is urgently needed to address the relevant issue of the role of WHO step II. For mild to moderate pain, weak opioids such as codeine, tramadol and dihydrocodeine should be given in combination with non-opioid analgesics [III, C]. As an alternative to weak opioids, consider low doses of strong opiods in combination with non-opioid analgesics [III, C]. Strong opioids (Table 5) are the mainstay of analgesic therapy in treating moderate–severe cancer-related pain, In some countries, pain relief is hampered by a lack of availability or barriers to accessibility to opioid analgesics [44.Cherny N.I. Baselga J. De Conno F. Radrbruch L. Formulary availability and regulatory barriers to accessibility of opioids for cancer pain in Europe: a report from the ESMO/EAPC Opioid policy initiative.Ann Oncol. 2010; 21: 615-626Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar]. Morphine, methadone, oxycodone, hydromorphone, fentanyl, alfentanyl, buprenorphine, heroin, levorphanol and oxymorphone are the most widely used strong opioids in Europe [33.Ripamonti C. Bandieri E. Cancer pain.Crit Rev Oncol Hematol. 2009; 70: 145-149Crossref PubMed Scopus (48) Google Scholar, 45.Ripamonti C. Bareggi C. Bruera E. Portenoy R.K. Pharmacology of opioid analgesia: clinical principles.Cancer Pain. Assessment and Management. Vol. 11. Cambridge University Press, Cambridge2010: 195-229Google Scholar]. In the last years in some countries, the consumption of oxycontin and the use of patches of fentanyl and buprenorphine has been increasing [46.Bandieri E. Chirarolanza A. Luppi M. Magrini N. Marata A.M. Ripamonti C. Prescription of opioids in Italy: everything but the morphine.Ann Oncol. 2009; 20: 961-962Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar]. However, there is no evidence from high quality comparative studies that other opioids are superior to morphine in terms of efficacy and tolerability.Table 5Comparison of selected opioids for moderate to severe pain (WHO step III)SubstanceRouteRelative effectiveness compared with oral morphineaThe relative effectiveness varies considerably in the published literature and among individual patients. Switching to another opiod should therefore be done cautiously with a dose reduction of the newly prescribed opioid.Maximal daily doseStarting dose without pretreatmentMorphine sulfateOral1No upper limitbThe maximal dose depends on tachyphylaxis.20–40 mgMorphinei.v.3No upper limitbThe maximal dose depends on tachyphylaxis.5–10 mgOxycodoneOral1.5–2No upper limitbThe maximal dose depends on tachyphylaxis.20 mgHydromorphoneOral7.5No upper limitbThe maximal dose depends on tachyphylaxis.8 mgFentanyl transdermalTTS+ 4cCalculated with conversion from mg/day to μg/h.No upper limitbThe maximal dose depends on tachyphylaxis.12 μg/hdNot usually used as first opioid (the 12 μg/h dose corresponds to about 30mg of oral morphine sulfate daily).BuprenorphineOral754 mg0.4 mgBuprenorphinei.v.1003 mg0.3–0.6 mgBuprenorphine transdermalTTS+ 4cCalculated with conversion from mg/day to μg/h.140 μg/h17.5–35μg/hMethadoneOral4–8–12eFactor 4 for daily morphine doses 300mg.No upper limitbThe maximal dose depends on tachyphylaxis.10 mgNicomorphineOral120 mg5 mgNicomorphinei.v.320 mg5 mgWHO, World Health Organization; i.v. intravenous.a The relative effectiveness varies considerably in the published literature and among individual patients. Switching to another opiod should therefore be done cautiously with a dose reduction of the newly prescribed opioid.b The maximal dose depends on tachyphylaxis.c Calculated with conversion from mg/day to μg/h.d Not usually used as first opioid (the 12 μg/h dose corresponds to about 30 mg of oral morphine sulfate daily).e Factor 4 for daily morphine doses 300 mg. Open table in a new tab WH
Referência(s)