Opioids in people with cancer-related pain.

INTRODUCTION: Up to 80% of people with cancer experience pain at some time during their illness, and most will need opioid analgesics. This review assesses how different opioid analgesics compare, in terms of both pain control and adverse effects, in people with cancer. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: what are the effects of opioids in treating cancer-related pain? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2007 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 22 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review, we present information relating to the effectiveness and safety of the following interventions: codeine, dihydrocodeine, transdermal fentanyl, hydromorphone, methadone, morphine, oxycodone, and tramadol.

Prescribing opioids in renal failure.

UNLABELLED: Opioids are commonly used in both cancer and noncancer pain. Many patients who require opioids have renal impairment. This can adversely influence the safety of opioids in these patients. OBJECTIVES: The objectives of this study were to (1) determine which opioids are most commonly prescribed in patients with renal impairment, (2) to identify differences in prescribing practices between two groups of physicians, and (3) to determine how renal impairment was recognized in this setting. DESIGN AND PARTICIPANTS: A questionnaire postal survey was sent out to renal and palliative medicine consultants in U.K. and Ireland. One hundred and seventy-eight (30.5 percent) questionnaires were completed. RESULTS: A larger proportion of renal than palliative medicine physicians prescribed morphine in patients with renal impairment. A significant number of physicians did not adjust doses of morphine or codeine. Palliative medicine physicians were more likely to prescribe opioids other than morphine, with the exception offentanyl which was widely used by both groups. Renal physicians were more likely to base their choice of opioid on glomerular filtration rate while palliative medicine physicians were more likely to be influenced by serum creatinine. CONCLUSIONS: Consensus guidelines drawing on expertise from both palliative and renal physicians are needed to promote safer use of opioids in this vulnerable patient group.

Clinical pharmacology and pharmacotherapy of opioid switching in cancer patients.

Pain is one of the most common and often most feared symptoms in patients with cancer. Ongoing or progressive pain is physically debilitating and has a marked impact on quality of life. Since a third of the population will die from cancer, and of these, 80% will experience severe pain in their final year of life, effective treatment of cancer-related pain remains both a high priority and an ongoing challenge in clinical practice. Individuals with moderate to severe cancer-related pain require treatment with strong analgesics, namely opioids. There is evidence to support the therapeutic maneuver of opioid switching in clinical practice, but further evidence is needed to elucidate the underlying mechanisms for interindividual differences in response to different opioids. Large, robust clinical trials will be needed if clinical differences among side-effect profiles of different opioids are to be clearly demonstrated. This review discusses candidate genes, which contribute to opioid response; many other genes have also been implicated in "pain" from animal or human studies. In order to continue to evaluate the genetic contributions to both pain susceptibility and analgesic response, further candidate genes need to be considered. Good pain control remains a high priority for clinicians and patients, and there is much work to be done to further individualize analgesic therapy for patients with cancer.

Transdermal fentanyl: informed prescribing is essential.

While morphine is historically the gold standard for the management of severe cancer pain, some patients either do not achieve adequate analgesia, or suffer intolerable side-effects. For these patients an alternative opioid is recommended. One such alternative is the potent mu opioid agonist fentanyl, delivered in a transdermal controlled release formulation. Similar to morphine, transdermal fentanyl is effective for the management of moderate to severe cancer pain. However, inappropriate prescribing of transdermal fentanyl, particularly in the clinical setting of unstable pain, can cause significant opioid toxicity, as highlighted in the case reports described.

Identifying neuropathic pain in patients with head and neck cancer: use of the Leeds Assessment of Neuropathic Symptoms and Signs Scale.

The Leeds Assessment of Neuropathic Symptoms and Signs Scale (LANSS) is a simple bedside test in two parts-a patient-completed questionnaire and a brief clinical assessment. Its diagnostic capabilities have never been tested in patients with cancer pain. To determine these we conducted a prospective study in outpatients with head and neck cancer. All patients with pain completed the LANSS and underwent a medical assessment with a palliative care physician, whose findings were then reviewed by a pain specialist blinded to the LANSS scores. We assessed acceptability and understanding of the LANSS by patients and calculated the sensitivity and specificity of total LANSS scores and subscores derived from the patient-completed section. Of 130 patients approached, 125 took part. 25 (20%) of these had cancer related pain, mean score on an 11 point numerical rating scale 6.3 (median 6.0, range 3-10). Average age was 60 years (median 60, range 27-84); 56% were male. LANSS completion time was about five minutes, and the procedure was acceptable to all patients. The pain specialist diagnosed neuropathic pain in 14/25 patients, in 13 of whom the neuropathic pain was part of a mixed pain picture. The LANSS correctly identified 11 of these cases (sensitivity 79%; specificity 100%). The patient-completed section alone had a sensitivity of 86% and a specificity of 91%. The LANSS is a simple and suitable screening test for neuropathic pain in patients with head and neck cancer related pain, although some modifications might improve it.

Symptoms in 400 patients referred to palliative care services: prevalence and patterns.

The demographics and prevalence of symptoms in patients at first referral to the different components of palliative care services were identified by a retrospective case note study of 400 patients referred to three palliative care centres in London, UK: Michael Sobell House, Mount Vernon Hospital; The North London Hospice; St Bartholomew's and the Royal London Hospitals. One hundred consecutive referrals to each of the following service components were analysed: a hospice inpatient service; a community team; an NHS hospital support team and an outpatient service. A standardized proforma was used to collect the data. Ninety five per cent (380/400) of patients referred had a cancer diagnosis. The five most prevalent symptoms overall were pain (64%), anorexia (34%), constipation (32%), weakness (32%) and dyspnoea (31%), which is similar to other published reports. However, the commonest symptoms and their prevalence varied depending on the service component to which the patient was referred. Patients referred to hospice and community services had the highest symptom burden (mean number of symptoms per patient 7.21 and 7.13, respectively). This study suggests that different patient subgroups may have different needs in terms of symptoms, which will be relevant for the planning and rationalization of palliative care services.

Plasma concentrations of morphine, morphine-6-glucuronide and morphine-3-glucuronide and their relationship with analgesia and side effects in patients with cancer-related pain.

Morphine, the recommended drug for the management of moderate to severe cancer pain, is metabolized predominantly to the glucuronides morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G). The quantitative clinical importance of these metabolites following the administration of oral morphine is unclear. This study investigates the relationship between plasma concentrations of morphine (M), M6G, M3G and clinical effects in patients receiving sustained release oral morphine for cancer-related pain. Peak and trough plasma concentrations of morphine and its metabolites were determined by high-performance liquid chromatography (HPLC). At corresponding time points, pain [Visual Analogue Scales (VAS), Verbal Rating Scales (VRS), Pain Relief Scores (PRS)] and toxicity (VAS and VRS) were assessed. Renal and liver function tests were performed. Forty-six patients were included in the study. There was a significant correlation between dose and both peak and trough plasma M, M6G and M3G (r > 0.60, P < 0.001 for each). Differences between peak and trough M, M6G, M3G, M+M6G, M6G:M, M3G:M and M3G:M6G were all significant (P < 0.001 for each). Pain was generally well controlled in the group, with a median VAS of 15 mm at the peak blood sampling time point. The differences between peak and trough values for VAS pain, VAS nausea and VAS drowsiness were not statistically significant (P = 0.078, 0.45 and 0.099, respectively). There were no differences in peak or trough morphine and metabolite concentrations or ratios between patients with low (< median) or high pain scores. Similarly, there was no significant relationship between high and low plasma concentrations and clinical effect. This study did not identify a simple relationship between plasma concentrations of morphine, morphine metabolites or metabolite ratios and clinical effects in patients with cancer and pain who were receiving chronic oral morphine therapy. Although overall pain control was good, there was marked interpatient variability in the dose of morphine and the plasma concentrations necessary to achieve this degree of analgesia.

A systematic review of hydromorphone in acute and chronic pain.

While morphine is historically the gold standard for the management of severe cancer pain, some patients either do not achieve adequate analgesia, or suffer intolerable side effects from this drug. For these patients, alternatives such as hydromorphone are recommended. This review explores the evidence for the efficacy of hydromorphone in the management of pain. A systematic search, from 1966 to 2000, of published and unpublished randomized trials that involved the administration of hydromorphone for both acute and chronic pain conditions in adults and children, was conducted. Forty-three studies were included in the review; 11 involved chronic cancer pain and 32 acute pain. Approximately half the studies received a low quality score. In addition, the heterogeneity of the studies precluded combination of data and results. Overall, hydromorphone appears to be a potent analgesic. The limited number of studies available suggests that there is little difference between hydromorphone and other opioids in terms of analgesic efficacy, adverse effect profile and patient preference. However, most studies involved small numbers of patients and wide ranges in equianalgesic dose ratios, making it difficult to determine real differences between interventions.