Alessandra Pigni

Is oral morphine still the first choice opioid for moderate to severe cancer pain? A systematic review within the European Palliative Care Research Collaborative guidelines project

The aim of this systematic review was to evaluate the evidence that oral morphine can be recommended as the first choice opioid in the treatment of moderate to severe cancer pain in updating the European Association for Palliative Care opioid recommendations. A systematic literature review was performed to update the 2007 Cochrane review ‘Oral morphine for cancer pain’. The literature search was conducted on MedLine, EMBASE and Cochrane Central Register of Controlled Trials databases. The search strategy, limited in time (from 1 July 2006 to 31 October 2009), was aimed to be as extensive as possible using both text words and MeSH/EMTREE terms; a hand search of the reference lists of identified papers was also performed. Randomized clinical trials, containing data on efficacy and/or side effects of morphine, were identified. Among the papers retrieved from the cited databases and the Cochrane review, 17 eligible studies, for a total of 2053 patients, and a meta-analysis were selected. These studies do not add significant information to the previous Cochrane review confirming the limitation of efficacy and tolerability data on opioid-naïve and non-selected populations of cancer patients treated with morphine and suggesting that oral morphine, oxycodone and hydromorphone have similar efficacy and toxicity in this patient population.

The role of paracetamol and nonsteroidal anti-inflammatory drugs in addition to WHO Step III opioids in the control of pain in advanced cancer. A systematic review of the literature

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol are used widely in the management of mild to moderate cancer pain and are frequently combined with opioids in the treatment of moderate to severe pain. Aim: To perform a systematic literature review of the evidence of the efficacy and toxicity of NSAIDs or paracetamol added to WHO Step III opioid treatment for cancer pain. Design and data sources: A systematic literature review of MedLine, EMBASE and Cochrane Central register of controlled trials database was carried out using both text words and MeSH/EMTREE terms. Results: Seven eligible papers were retrieved from the new search and five from the Cochrane review. Five of seven studies showed an additive effect of NSAIDs when combined with opioids either by improving analgesia (three studies) or by reducing the opioid dose (two studies). Paracetamol was only marginally effective in one of five trials. The study designs were not adequate to assess differences in side effects between the opioids alone and opioids in combination with NSAIDs or paracetamol. Conclusions: The evidence from the available clinical trials is of limited amount and quality, but it weakly supports the proposal that the addition of an NSAIDs to WHO Step III opioids can improve analgesia or reduce opioid dose requirement. There is insufficient evidence to support the use of paracetamol in combination with Step III opioids. Data on the toxicity of NSAIDs in this indication are insufficient owing to the small number of patients and the short duration of treatment reported in the studies.

Multiple Loci Modulate Opioid Therapy Response for Cancer Pain

Purpose: Patients treated with opioid drugs for cancer pain experience different relief responses, raising the possibility that genetic factors play a role in opioid therapy outcome. In this study, we tested the hypothesis that genetic variations may control individual response to opioid drugs in cancer patients. Experimental Design: We tested 1 million single-nucleotide polymorphisms (SNP) in European cancer patients, selected in a first series, for extremely poor (pain relief ≤40%; n = 145) or good (pain relief ≥90%; n = 293) responses to opioid therapy using a DNA-pooling approach. Candidate SNPs identified by SNP-array were genotyped in individual samples constituting DNA pools as well as in a second series of 570 patients. Results: Association analysis in 1,008 cancer patients identified eight SNPs significantly associated with pain relief at a statistical threshold of P < 1.0 × 10−3, with rs12948783, upstream of the RHBDF2 gene, showing the best statistical association (P = 8.1 × 10−9). Functional annotation analysis of SNP-tagged genes suggested the involvement of genes acting on processes of the neurologic system. Conclusion: Our results indicate that the identified SNP panel can modulate the response of cancer patients to opioid therapy and may provide a new tool for personalized therapy of cancer pain. Clin Cancer Res; 17(13); 4581–7. ©2011 AACR.

The role of hydromorphone in cancer pain treatment: a systematic review

The aim of this systematic review is to evaluate the scientific evidence for the efficacy and side effects of hydromorphone in the management of moderate to severe cancer pain. Randomized and non-randomized clinical trials, reporting data on efficacy and/or side effects of hydromorphone, were identified. Thirteen eligible studies, involving 1208 patients, were selected. Seven studies compared hydromorphone with other opioids (five with morphine, one with oxycodone and one with fentanyl and buprenorphine) and five of them were randomized controlled trials (RCTs). Most of the studies were conducted on patients already receiving opioid treatment, often at stabilized doses, and most had methodological limitations. The RCTs comparing hydromorphone with morphine and oxycodone showed similar analgesic results, while the comparison of side effects showed minor differences, not consistent across studies. Due to clinical and methodological heterogeneity of the studies, a meta-analysis was not performed. In conclusion there is evidence to support the efficacy and tolerability of hydromorphone for moderate to severe cancer pain as an alternative to morphine and oxycodone, while there is no evidence to demonstrate its superiority or inferiority in comparison with morphine as the first choice opioid for the same indication.

Evidence on the analgesic role of bisphosphonates and denosumab in the treatment of pain due to bone metastases: A systematic review within the European Association for Palliative Care guidelines project

Background: Bisphosphonates and denosumab are well-established therapies to reduce the frequency and severity of skeletal-related events in patients with bone metastasis. However, the analgesic effect of these medications on bone pain is uncertain. Aim: To identify, critically appraise and synthesize existing evidence to answer the following questions: ‘In adult patients with metastatic bone pain, what is the evidence that bisphosphonates and denosumab are effective and safe in controlling pain?’ and ‘What is the most appropriate schedule of bisphosphonate/denosumab administration to control bone pain?’. This review also updates the 2002 Cochrane review ‘Bisphosphonates for the relief of pain secondary to bone metastases’. Design: Standard systematic review and narrative synthesis. Data sources: MEDLINE, EMBASE and Cochrane CENTRAL databases were searched for relevant articles published through 31 January 2014. A manual search was also performed. Study inclusion criteria were: a) conducted in adult patients; b) randomized controlled trial or meta-analisys; c) reported efficacy of bisphosphonates or denosumab on pain and/or decribed side effects versus placebo or other bisphosphonate; and d) English language. Results: The database search yielded 1585 studies, of which 43 (enrolling 8595 and 7590 patients, respectively, in bisphosphonate and denosumab trials) met the inclusion criteria. Twenty-two (79%) of the 28 placebo-controlled trials found no analgesic benefit for bisphosphonates. None of the denosumab studies assessed direct pain relief. Conclusion: Evidence to support an analgesic role for bisphosphonates and denosumab is weak. Bisphosphonates and denosumab appear to be beneficial in preventing pain by delaying the onset of bone pain rather than by producing an analgesic effect per se.

The validity of average 8-h pain intensity assessment in cancer patients

Aim of this study was to validate the use of subjective average pain assessment over an 8‐h time period to evaluate cancer pain intensity.

Minimally invasive procedures for the management of vertebral bone pain due to cancer: The EAPC recommendations

Abstract Background: Image-guided percutaneous ablation methods have proved effective for treatment of benign bone tumors and for palliation of metastases involving the bone. However, the role of these techniques is controversial and has to be better defined in the setting of palliative care. Methods: A systematic review of the existing data regarding minimally invasive techniques for the pain management of vertebral bone metastases was performed by experts of the European Palliative Care Research Network. Results: Only five papers were taken into consideration after performing rigorous screening according to inclusion and exclusion criteria (low number of patients, retrospective series, proceedings). Discussion: According to the present data a recommendation should be made to perform kiphoplasty in patients with vertebral tumors or metastases. However, the strength of this recommendation was based on one randomized controlled study. Several weaknesses and low quality of study design were observed with other techniques. Conclusion: Further randomized controlled trials are required to improve the strength of evidence available to suggest these procedures on large scale. Until then, the balance of evidence favors the use of these procedures in a small select cohort of patients with severe and disabling back pain refractory to medical therapy.