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The Cochrane Database of Systematic... Aug 2021This is an update of the original Cochrane Review first published in Issue 10, 2016. For people with advanced cancer, the prevalence of pain can be as high as 90%.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of the original Cochrane Review first published in Issue 10, 2016. For people with advanced cancer, the prevalence of pain can be as high as 90%. Cancer pain is a distressing symptom that tends to worsen as the disease progresses. Evidence suggests that opioid pharmacotherapy is the most effective of these therapies. Hydromorphone appears to be an alternative opioid analgesic which may help relieve these symptoms.
OBJECTIVES
To determine the analgesic efficacy of hydromorphone in relieving cancer pain, as well as the incidence and severity of any adverse events.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase and clinical trials registers in November 2020. We applied no language, document type or publication status limitations to the search.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared hydromorphone with placebo, an alternative opioid or another active control, for cancer pain in adults and children. Primary outcomes were participant-reported pain intensity and pain relief; secondary outcomes were specific adverse events, serious adverse events, quality of life, leaving the study early and death.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data. We calculated risk ratio (RR) and 95% confidence intervals (CI) for binary outcomes on an intention-to-treat (ITT) basis. We estimated mean difference (MD) between groups and 95% CI for continuous data. We used a random-effects model and assessed risk of bias for all included studies. We assessed the evidence using GRADE and created three summary of findings tables.
MAIN RESULTS
With four new identified studies, the review includes a total of eight studies (1283 participants, with data for 1181 participants available for analysis), which compared hydromorphone with oxycodone (four studies), morphine (three studies) or fentanyl (one study). All studies included adults with cancer pain, mean age ranged around 53 to 59 years and the proportion of men ranged from 42% to 67.4%. We judged all the studies at high risk of bias overall because they had at least one domain with high risk of bias. We found no studies including children. We did not complete a meta-analysis for the primary outcome of pain intensity due to skewed data and different comparators investigated across the studies (oxycodone, morphine and fentanyl). Comparison 1: hydromorphone compared with placebo We identified no studies comparing hydromorphone with placebo. Comparison 2: hydromorphone compared with oxycodone Participant-reported pain intensity We found no clear evidence of a difference in pain intensity (measured using a visual analogue scale (VAS)) in people treated with hydromorphone compared with those treated with oxycodone, but the evidence is very uncertain (3 RCTs, 381 participants, very low-certainty evidence). Participant-reported pain relief We found no studies reporting participant-reported pain relief. Specific adverse events We found no clear evidence of a difference in nausea (RR 1.13 95% CI 0.74 to 1.73; 3 RCTs, 622 participants), vomiting (RR 1.18, 95% CI 0.72 to 1.94; 3 RCTs, 622 participants), dizziness (RR 0.91, 95% CI 0.58 to 1.44; 2 RCTs, 441 participants) and constipation (RR 0.92, 95% CI 0.72 to 1.19; 622 participants) (all very low-certainty evidence) in people treated with hydromorphone compared with those treated with oxycodone, but the evidence is very uncertain. Quality of life We found no studies reporting quality of life. Comparison 3: hydromorphone compared with morphine Participant-reported pain intensity We found no clear evidence of a difference in pain intensity (measured using the Brief Pain Inventory (BPI) or VAS)) in people treated with hydromorphone compared with those treated with morphine, but the evidence is very uncertain (2 RCTs, 433 participants; very low-certainty evidence). Participant-reported pain relief We found no clear evidence of a difference in the number of clinically improved participants, defined by 50% or greater pain relief rate, in the hydromorphone group compared with the morphine group, but the evidence is very uncertain (RR 0.99, 95% CI 0.84 to 1.18; 1 RCT, 233 participants; very low-certainty evidence). Specific adverse events At 24 days of treatment, morphine may reduce constipation compared with hydromorphone, but the evidence is very uncertain (RR 1.56, 95% CI 1.12 to 2.17; 1 RCT, 200 participants; very low-certainty evidence). We found no clear evidence of a difference in nausea (RR 0.94, 95% CI 0.66 to 1.30; 1 RCT, 200 participants), vomiting (RR 0.87, 95% CI 0.58 to 1.31; 1 RCT, 200 participants) and dizziness (RR 1.15, 95% CI 0.71 to 1.88; 1 RCT, 200 participants) (all very low-certainty evidence) in people treated with hydromorphone compared with those treated with morphine, but the evidence is very uncertain. Quality of life We found no studies reporting quality of life. Comparison 4: hydromorphone compared with fentanyl Participant-reported pain intensity We found no clear evidence of a difference in pain intensity (measured by numerical rating scale (NRS)) at 60 minutes in people treated with hydromorphone compared with those treated with fentanyl, but the evidence is very uncertain (1 RCT, 82 participants; very low-certainty evidence). Participant-reported pain relief We found no studies reporting participant-reported pain relief. Specific adverse events We found no studies reporting specific adverse events. Quality of life We found no studies reporting quality of life.
AUTHORS' CONCLUSIONS
The evidence of the benefits and harms of hydromorphone compared with other analgesics is very uncertain. The studies reported some adverse events, such as nausea, vomiting, dizziness and constipation, but generally there was no clear evidence of a difference between hydromorphone and morphine, oxycodone or fentanyl for this outcome. There is insufficient evidence to support or refute the use of hydromorphone for cancer pain in comparison with other analgesics on the reported outcomes. Further research with larger sample sizes and more comprehensive outcome data collection is required.
Topics: Adult; Analgesics, Opioid; Cancer Pain; Child; Humans; Hydromorphone; Male; Middle Aged; Morphine; Neoplasms; Oxycodone
PubMed: 34350974
DOI: 10.1002/14651858.CD011108.pub3 -
Journal of Opioid Management 2017We performed a systematic review to answer the question, "Does the introduction of an opioid analgesic with abuse deterrent properties result in reduced overall abuse of... (Review)
Review
OBJECTIVE
We performed a systematic review to answer the question, "Does the introduction of an opioid analgesic with abuse deterrent properties result in reduced overall abuse of the drug in the community?"
DESIGN
We included opioid analgesics with abuse deterrent properties (hydrocodone, morphine, oxycodone) with results restricted to the metasearch term "delayed onset," English language, use in humans, and publication years 2009-2016. All articles that contained data evaluating misuse, abuse, overdose, addiction, and death were included. The results were categorized using the Bradford-Hill criteria.
RESULTS
We included 44 reports: hydrocodone (n = 7), morphine (n = 5), or oxycodone (n = 32) with Food and Drug Administration-approved Categories 1, 2, or 3 abuse deterrent labeling. The data currently available support the Hill criteria of strength (effect size), consistency (reproducibility), temporality, plausibility, and coherence. There was insufficient or no information available for the criteria of biological gradient, experiment, and analogy. We also assessed confounding factors and bias, which indicated that both were present and substantial in magnitude.
CONCLUSIONS
Our analysis found that only oxycodone extended release (ER) had information available to evaluate abuse deterrence in the community. In Australia, Canada, and the United States, reformulation of oxycodone ER was followed by marked reduction in measures of abuse. The precise extent of reduced abuse cannot be calculated because of heterogeneous data sets, but the reported reductions ranged from 10 to 90 percent depending on the measure and the duration of follow-up.
Topics: Abuse-Deterrent Formulations; Analgesics, Opioid; Delayed-Action Preparations; Drug Compounding; Humans; Opioid-Related Disorders; Protective Factors; Risk Factors; Time Factors
PubMed: 29308584
DOI: 10.5055/jom.2017.0415 -
The Cochrane Database of Systematic... Aug 2017Many people with cancer experience moderate to severe pain that requires treatment with strong opioids, such as oxycodone and morphine. Strong opioids are, however, not... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many people with cancer experience moderate to severe pain that requires treatment with strong opioids, such as oxycodone and morphine. Strong opioids are, however, not effective for pain in all people, neither are they well-tolerated by all people. The aim of this review was to assess whether oxycodone is associated with better pain relief and tolerability than other analgesic options for adults with cancer pain. This is an updated version of the original Cochrane review published in 2015, Issue 2 on oxycodone for cancer-related pain.
OBJECTIVES
To assess the effectiveness and tolerability of oxycodone by any route of administration for pain in adults with cancer.
SEARCH METHODS
For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE and MEDLINE In-Process (Ovid), Embase (Ovid), Science Citation Index, Conference Proceedings Citation Index - Science (ISI Web of Science), BIOSIS (ISI), and PsycINFO (Ovid) to November 2016. We also searched four trial registries, checked the bibliographic references of relevant studies, and contacted the authors of the included studies. We applied no language, date, or publication status restrictions.
SELECTION CRITERIA
We included randomised controlled trials (parallel group or cross-over) comparing oxycodone (any formulation or route of administration) with placebo or an active drug (including oxycodone) for cancer background pain in adults by examining pain intensity/relief, adverse events, quality of life, and participant preference.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the included studies using standard Cochrane methodology. We meta-analysed pain intensity data using the generic inverse variance method, and adverse events using the Mantel-Haenszel method, or summarised these data narratively along with the quality of life and participant preference data. We assessed the overall quality of the evidence using GRADE.
MAIN RESULTS
For this update, we identified six new studies (1258 participants) for inclusion. In total, we included 23 studies which enrolled/randomised 2648 participants, with 2144 of these analysed for efficacy and 2363 for safety. The studies examined a number of different drug comparisons.Pooled analysis of three of the four studies comparing controlled-release (CR) oxycodone to immediate-release (IR) oxycodone showed that the ability of CR and IR oxycodone to provide pain relief were similar (standardised mean difference (SMD) 0.1, 95% confidence interval (CI) -0.06 to 0.26; low quality evidence). Pooled analyses of adverse events showed no significant differences between CR and IR oxycodone for asthenia (risk ratio (RR) 0.58, 95% CI 0.2 to 1.68), confusion (RR 0.78, 95% CI 0.2 to 3.02), constipation (RR 0.71, 95% CI 0.45 to 1.13), dizziness/lightheadedness (RR 0.74, 95% CI 0.4 to 1.37), drowsiness/somnolence (RR 1.03, 95% CI 0.69 to 1.54), dry mouth (RR 1.14, 95% CI 0.48 to 2.75), insomnia (RR 1.04, 95% CI 0.31 to 3.53), nausea (RR 0.85, 95% CI 0.56 to 1.28), nervousness (RR 0.57, 95% CI 0.2 to 1.64), pruritus (RR 1.46, 95% CI 0.65 to 3.25), vomiting (RR 0.66, 95% CI 0.38 to 1.15), and discontinuation due to adverse events (RR 0.6, 95% CI 0.29 to 1.22). The quality of the evidence was very low for all these adverse events. Three of the four studies found similar results for treatment acceptability.Pooled analysis of seven of the nine studies comparing CR oxycodone to CR morphine indicated that pain relief was significantly better after treatment with CR morphine than CR oxycodone (SMD 0.14, 95% CI 0.01 to 0.27; low quality evidence). However, sensitivity analysis did not corroborate this result (SMD 0.12, 95% CI -0.02 to 0.26).Pooled analyses of adverse events showed no significant differences between CR oxycodone and CR morphine for confusion (RR 1.01 95% CI 0.78 to 1.31), constipation (RR 0.98, 95% CI 0.82 to 1.16), dizziness/lightheadedness (RR 0.76, 95% CI 0.33 to 1.76), drowsiness/somnolence (RR 0.9, 95% CI 0.75 to 1.08), dry mouth (RR 1.01, 95% CI 0.8 to 1.26), dysuria (RR 0.71, 95% CI 0.4 to 1.26), nausea (RR 1.02, 95% CI 0.82 to 1.26), pruritus (RR 0.81, 95% CI 0.51 to 1.29), vomiting (RR 0.94, 95% CI 0.68 to 1.29), and discontinuation due to adverse events (RR 1.06, 95% CI 0.43 to 2.6). However, the RR for hallucinations was significantly lower after treatment with CR oxycodone compared to CR morphine (RR 0.52, 95% CI 0.28 to 0.97). The quality of the evidence was very low for all these adverse events. There were no marked differences in treatment acceptability or quality of life ratings.The remaining studies either compared oxycodone in various formulations or compared oxycodone to different alternative opioids. None found any clear superiority or inferiority of oxycodone for cancer pain, neither as an analgesic agent nor in terms of adverse event rates and treatment acceptability.The quality of this evidence base was limited by the high or unclear risk of bias of the studies and by imprecision due to low or very low event rates or participant numbers for many outcomes.
AUTHORS' CONCLUSIONS
The conclusions have not changed since the previous version of this review. The data suggest that oxycodone offers similar levels of pain relief and overall adverse events to other strong opioids including morphine. Although we identified a clinically insignificant benefit on pain relief in favour of CR morphine over CR oxycodone, this did not persist following sensitivity analysis and so we do not consider this important. However, in this updated analysis, we found that hallucinations occurred less often with CR oxycodone than with CR morphine, but the quality of this evidence was very low so this finding should be treated with utmost caution. Our conclusions are consistent with other reviews and suggest that while the reliability of the evidence base is low, given the absence of important differences within this analysis it seems unlikely that larger head to head studies of oxycodone versus morphine are justified, although well-designed trials comparing oxycodone to other strong analgesics may well be useful. For clinical purposes, oxycodone or morphine can be used as first-line oral opioids for relief of cancer pain in adults.
Topics: Aged; Analgesics, Opioid; Cancer Pain; Constipation; Delayed-Action Preparations; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Morphine; Nausea; Neoplasms; Oxycodone; Pain Measurement; Quality of Life; Randomized Controlled Trials as Topic; Sleep Stages; Vomiting
PubMed: 28829910
DOI: 10.1002/14651858.CD003870.pub6 -
The Cochrane Database of Systematic... Sep 2016This review replaces part of an earlier review that evaluated oxycodone for both neuropathic pain and fibromyalgia, which has now been split into separate reviews for... (Review)
Review
BACKGROUND
This review replaces part of an earlier review that evaluated oxycodone for both neuropathic pain and fibromyalgia, which has now been split into separate reviews for the two conditions. This review will consider pain in fibromyalgia only.Opioid drugs are commonly used to treat fibromyalgia, but they may not be beneficial for people with this condition. Most reviews have examined all opioids together. This review sought evidence specifically for oxycodone, at any dose, and by any route of administration.
OBJECTIVES
To assess the analgesic efficacy and adverse events of oxycodone for treating pain in fibromyalgia in adults.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE for randomised controlled trials from inception to 25 July 2016. We also searched the reference lists of retrieved studies and reviews, and searched online clinical trial registries.
SELECTION CRITERIA
We planned to include randomised, double-blind trials of eight weeks' duration or longer, comparing oxycodone (alone or in fixed-dose combination with naloxone) with placebo or another active treatment. We did not include observational studies.
DATA COLLECTION AND ANALYSIS
The plan was for two independent review authors to extract data and assess trial quality and potential bias. Where pooled analysis was possible, we planned to use dichotomous data to calculate risk ratio and numbers needed to treat for one additional event, using standard methods.
MAIN RESULTS
No study satisfied the inclusion criteria. Effects of interventions were not assessed as there were no included studies. We have only very low quality evidence and are very uncertain about estimates of benefit and harm.
AUTHORS' CONCLUSIONS
There is no randomised trial evidence to support or refute the suggestion that oxycodone, alone or in combination with naloxone, reduces pain in fibromyalgia.
PubMed: 27582266
DOI: 10.1002/14651858.CD012329 -
The Cochrane Database of Systematic... May 2015Agitation is a common experience for people living with dementia, particularly as day-to-day function and cognition start to decline more. At the present time there are... (Review)
Review
BACKGROUND
Agitation is a common experience for people living with dementia, particularly as day-to-day function and cognition start to decline more. At the present time there are limited pharmacological options for relieving agitation and little is known about the safety and efficacy of opioid drugs in this setting.
OBJECTIVES
To determine the clinical efficacy and safety of opioids for agitation in people with dementia.
SEARCH METHODS
We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialized Register, on 13 June 2014 using the terms: narcotic OR opioid OR opium OR morphine OR buprenorphine OR codeine OR dextromoramide OR diphenoxylate OR dipipanone OR dextropropoxyphene OR propoxyphene OR diamorphine OR dihydrocodeine OR alfentanil OR fentanyl OR remifentanil OR meptazinol OR methadone OR nalbuphine OR oxycodone OR papaveretum OR pentazocine OR meperidine OR pethidine OR phenazocine OR hydrocodone OR hydromorphone OR levorphanol OR oxymorphone OR butorphanol OR dezocine OR sufentanil OR ketobemidone.ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases such as MEDLINE, EMBASE and PscyINFO, as well as numerous trial registries and grey literature sources.
SELECTION CRITERIA
Randomised, controlled trials of opioids compared to placebo for agitation in people with dementia.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed the studies identified by the search against the inclusion criteria.
MAIN RESULTS
There are currently no completed randomised, placebo controlled trials of opioids for agitation in dementia. There are two potentially relevant trials still in progress.
AUTHORS' CONCLUSIONS
We found insufficient evidence to establish the clinical efficacy and safety of opioids for agitation in people with dementia. There remains a lack of data to determine if or when opioids either relieve or exacerbate agitation. More evidence is needed to guide the effective, appropriate and safe use of opioids in dementia.
Topics: Analgesics, Opioid; Dementia; Humans; Psychomotor Agitation
PubMed: 25972091
DOI: 10.1002/14651858.CD009705.pub2 -
Experimental Biology and Medicine... Nov 2023The opioid epidemic has become a serious national crisis in the United States. An indepth systematic analysis of opioid-related adverse events (AEs) can clarify the...
The opioid epidemic has become a serious national crisis in the United States. An indepth systematic analysis of opioid-related adverse events (AEs) can clarify the risks presented by opioid exposure, as well as the individual risk profiles of specific opioid drugs and the potential relationships among the opioids. In this study, 92 opioids were identified from the list of all Food and Drug Administration (FDA)-approved drugs, annotated by RxNorm and were classified into 13 opioid groups: buprenorphine, codeine, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, tapentadol, and tramadol. A total of 14,970,399 AE reports were retrieved and downloaded from the FDA Adverse Events Reporting System (FAERS) from 2004, Quarter 1 to 2020, Quarter 3. After data processing, Empirical Bayes Geometric Mean (EBGM) was then applied which identified 3317 pairs of potential risk signals within the 13 opioid groups. Based on these potential safety signals, a comparative analysis was pursued to provide a global overview of opioid-related AEs for all 13 groups of FDA-approved prescription opioids. The top 10 most reported AEs for each opioid class were then presented. Both network analysis and hierarchical clustering analysis were conducted to further explore the relationship between opioids. Results from the network analysis revealed a close association among fentanyl, oxycodone, hydrocodone, and hydromorphone, which shared more than 22 AEs. In addition, much less commonly reported AEs were shared among dihydrocodeine, meperidine, oxymorphone, and tapentadol. On the contrary, the hierarchical clustering analysis further categorized the 13 opioid classes into two groups by comparing the full profiles of presence/absence of AEs. The results of network analysis and hierarchical clustering analysis were not only consistent and cross-validated each other but also provided a better and deeper understanding of the associations and relationships between the 13 opioid groups with respect to their adverse effect profiles.
Topics: Analgesics, Opioid; Bayes Theorem; Data Mining; Fentanyl; Hydrocodone; Hydromorphone; Meperidine; Oxycodone; Oxymorphone; Tapentadol; United States
PubMed: 38158803
DOI: 10.1177/15353702231211860 -
The Cochrane Database of Systematic... Sep 2015A large proportion of people with advanced cancer will experience moderate to severe pain. Tapentadol is a novel, centrally acting analgesic medicine acting at the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A large proportion of people with advanced cancer will experience moderate to severe pain. Tapentadol is a novel, centrally acting analgesic medicine acting at the μ-opioid receptor and inhibiting noradrenaline reuptake. The efficacy of tapentadol is stated to be comparable to morphine and oxycodone.
OBJECTIVES
To assess the analgesic efficacy of tapentadol for the relief of cancer pain in adults, and the adverse events associated with its use in clinical trials.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE from January 2005 to July 2015, together with reference lists of retrieved papers and review articles, and two clinical trial registries. Searches started from 2005 because this covered the period during which clinical trials were conducted. We contacted the manufacturer of tapentadol in the UK to find additional trials not identified by electronic searches. We did not restrict searches by language.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of tapentadol compared with placebo or active controls in adults with moderate to severe cancer pain. Pain had to be measured using a validated assessment tool, and studies had to include at least 10 participants per treatment arm.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data using a standard form and assessed risk of bias. We extracted available data on study design, participant details, interventions, and outcomes, including analgesic outcome measures, withdrawals, and adverse events.
MAIN RESULTS
We included four studies with 1029 participants. All the studies used a parallel-group design, and included an initial titration phase to determine the maximum effective and tolerated dose, followed by a maintenance phase. Tapentadol medication was taken twice daily and doses ranged from 50 to 500 mg per day. Rescue medication (morphine or oxycodone immediate-release) was available to participants in all studies.Overall, 440 participants were randomised in classically designed RCTs, and 589 participants were enrolled in enriched-enrolment, randomised-withdrawal (EERW) trials. A total of 476 participants were randomised to titration with tapentadol and 338 participants took tapentadol throughout the maintenance phase of their trial.All studies used numerical rating scores, Patient Global Impression of Change scores, and use of rescue medication as measures of efficacy, and all reported on adverse events and withdrawals.All studies enrolled fewer than 200 participants per treatment arm and were therefore at risk of overestimating efficacy. One study was terminated early due to problems with supply of rescue medication, with fewer than 20 participants enrolled per treatment arm in the maintenance phase of the trial. We judged another study at high risk of bias due to an open-label design.There were insufficient data for pooling and statistical analysis. Response rates for pain intensity were comparable across treatment groups in each study. In one EERW study, response rates were high across both treatment and placebo arms during the maintenance phase (62% tapentadol, 69% morphine, 50% placebo). For pain relief, tapentadol is no more and no less effective than oxycodone or morphine (low quality evidence).Treatment emergent adverse event rates were high, approximately 50% to 90%. The most common adverse events were gastrointestinal (nausea, vomiting, constipation) (low quality evidence). There was no advantage of tapentadol over morphine or oxycodone in terms of serious adverse events. The number of people experiencing effects on consciousness, appetite, or thirst was low.
AUTHORS' CONCLUSIONS
Information from RCTs on the effectiveness and tolerability of tapentadol was limited. The available studies were of moderate or small size and used different designs, which prevented pooling of data. Pain relief and adverse events were comparable between the tapentadol and morphine and oxycodone groups.
Topics: Adult; Humans; Neoplasms; Pain; Phenols; Randomized Controlled Trials as Topic; Receptors, Opioid, mu; Tapentadol
PubMed: 26403220
DOI: 10.1002/14651858.CD011460.pub2 -
Cancer Treatment Reviews Apr 2024Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and treatment of OIC osmotic (e.g. polyethylene glycol) and stimulant (e.g. bisacodyl) laxatives are widely used. Newer drugs such as the peripherally acting µ-opioid receptor antagonists (PAMORAs) and naloxone in a fixed combination with oxycodone have become available for the management of OIC. This systematic review and meta-analysis aims to give an overview of the scientific evidence on pharmacological strategies for the prevention and treatment of OIC in cancer patients.
METHODS
A systematic search in PubMed, Embase, Web of Science and the Cochrane Library was completed from inception up to 22 October 2022. Randomized and non-randomized studies were systematically selected. Bowel function and adverse drug events were assessed.
RESULTS
Twenty trials (prevention: five RCTs and three cohort studies; treatment: ten RCTs and two comparative cohort studies) were included in the review. Regarding the prevention of OIC, three RCTs compared laxatives with other laxatives, finding no clear differences in effectivity of the laxatives used. One cohort study showed a significant benefit of magnesium oxide compared with no laxative. One RCT found a significant benefit for the PAMORA naldemedine compared with magnesium oxide. Preventive use of oxycodone/naloxone did not show a significant difference in two out of three other studies compared to oxycodone or fentanyl. A meta-analysis was not possible. Regarding the treatment of OIC, two RCTs compared laxatives, of which one RCT found that polyethylene glycol was significantly more effective than sennosides. Seven studies compared an opioid antagonist (naloxone, methylnaltrexone or naldemedine) with placebo and three studies compared different dosages of opioid antagonists. These studies with opioid antagonists were used for the meta-analysis. Oxycodone/naloxone showed a significant improvement in Bowel Function Index compared to oxycodone with laxatives (MD -13.68; 95 % CI -18.38 to -8.98; I = 58 %). Adverse drug event rates were similar amongst both groups, except for nausea in favour of oxycodone/naloxone (RR 0.51; 95 % CI 0.31-0.83; I = 0 %). Naldemedine (NAL) and methylnaltrexone (MNTX) demonstrated significantly higher response rates compared to placebo (NAL: RR 2.07, 95 % CI 1.64-2.61, I = 0 %; MNTX: RR 3.83, 95 % CI 2.81-5.22, I = 0 %). With regard to adverse events, abdominal pain was more present in treatment with methylnaltrexone and diarrhea was significantly more present in treatment with naldemedine. Different dosages of methylnaltrexone were not significantly different with regard to both efficacy and adverse drug event rates.
CONCLUSIONS
Magnesium oxide and naldemedine are most likely effective for prevention of OIC in cancer patients. Naloxone in a fixed combination with oxycodone, naldemedine and methylnaltrexone effectively treat OIC in cancer patients with acceptable adverse events. However, their effect has not been compared to standard (osmotic and stimulant) laxatives. More studies comparing standard laxatives with each other and with opioid antagonists are necessary before recommendations for clinical practice can be made.
Topics: Humans; Laxatives; Analgesics, Opioid; Narcotic Antagonists; Constipation; Oxycodone; Opioid-Induced Constipation; Magnesium Oxide; Cohort Studies; Naloxone; Polyethylene Glycols; Neoplasms; Drug-Related Side Effects and Adverse Reactions; Quaternary Ammonium Compounds; Naltrexone
PubMed: 38452708
DOI: 10.1016/j.ctrv.2024.102704 -
BMJ Supportive & Palliative Care Jun 2018To assess the efficacy, tolerability and acceptability of oxycodone for cancer pain in adults METHODS: We searched CENTRAL, MEDLINE, MEDLINE In-Process, Embase, SCI,... (Review)
Review
OBJECTIVES
To assess the efficacy, tolerability and acceptability of oxycodone for cancer pain in adults METHODS: We searched CENTRAL, MEDLINE, MEDLINE In-Process, Embase, SCI, Conference Proceedings Citation Index-Science, BIOSIS, PsycINFO and four trials registries to November 2016.
RESULTS
We included 23 randomised controlled trials with 2144 patients analysed for efficacy and 2363 for safety. Meta-analyses showed no significant differences between controlled-release (CR) and immediate-release oxycodone in pain intensity or adverse events but did show significantly better pain relief after treatment with CR morphine compared with CR oxycodone. However, sensitivity analysis did not corroborate this result. Meta-analyses of the adverse events showed a significantly lower risk of hallucinations after treatment with CR oxycodone compared with CR morphine, but no other differences. The remaining studies either compared oxycodone in various formulations or compared oxycodone to different alternative opioids. None found any clear superiority or inferiority of oxycodone in pain relief or adverse events. The quality of this evidence base was limited by the high/unclear risk of bias of the studies and the low event rates for many outcomes.
CONCLUSIONS
Oxycodone offers similar levels of pain relief and adverse events to other strong opioids. However, hallucinations occurred less with CR oxycodone than with CR morphine, but the quality of this evidence was very low, so this finding should be treated with utmost caution. Our conclusions are consistent with other reviews and suggest that oxycodone can be used first line as an alternative to morphine. However, because it is cheaper, morphine generally remains the first-line opioid of choice.
Topics: Analgesics, Opioid; Cancer Pain; Humans; Oxycodone; Pain Management; Patient Preference; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 29331953
DOI: 10.1136/bmjspcare-2017-001457 -
The Cochrane Database of Systematic... Oct 2016Cancer pain is an important and distressing symptom that tends to increase in frequency and intensity as the cancer advances. For people with advanced cancer, the... (Review)
Review
BACKGROUND
Cancer pain is an important and distressing symptom that tends to increase in frequency and intensity as the cancer advances. For people with advanced cancer, the prevalence of pain can be as high as 90%. It has been estimated that 30% to 50% of people with cancer categorise their pain as moderate to severe, with between 75% and 90% of people with cancer experiencing pain that they describe as having a major impact on their daily life. Epidemiological studies suggest that approximately 15% of people with cancer pain fail to experience acceptable pain relief with conventional management. Uncontrolled pain can lead to physical and psychological distress and can, consequently, have a drastic effect on people's quality of life.
OBJECTIVES
To determine the analgesic efficacy of hydromorphone in relieving cancer pain, as well as the incidence and severity of any adverse events.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase and clinical trials registers up to April 2016. There were no language, document type or publication status limitations applied in the search.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared hydromorphone with placebo or other active pain medication for cancer pain in both adults and children. The four main outcomes selected have previously been identified as important to people with cancer; pain no worse than mild pain, and the impact of the treatment on consciousness, appetite and thirst. We did not consider physician-, nurse- or carer-reported measures of pain.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We used a random-effects model and assessed the risk of bias for all included studies. A meta-analysis was not completed on any of the primary outcomes in this review due to the lack of data. We assessed the evidence using GRADE and created two 'Summary of findings' tables.
MAIN RESULTS
We included four studies (604 adult participants), which compared hydromorphone to oxycodone (two studies) or morphine (two studies). Overall, the included studies were at low or unclear risk of bias, rated unclear due to unknown status of blinding of outcome assessment; we rated three studies at high risk of bias for potential conflict of interest. Data for 504 participants were available for analysis. We collected data on endpoint participant-reported pain intensity measured with a visual analogue scale (VAS) (mean ± standard deviation (SD): hydromorphone 28.86 ± 17.08, n = 19; oxycodone 30.30 ± 25.33, n = 12; scale from 0 to 100 with higher score indicating worse pain), and Brief Pain Inventory (BPI) 24 hours worst pain subscale (mean ± SD: hydromorphone 3.5 ± 2.9, n = 99; morphine 4.3 ± 3.0, n = 101, scale from 0 to 10 with higher score indicating worse pain). The data demonstrated a similar effect between groups with both comparisons. The pain intensity data showed that participants in all four trials achieved no worse than mild pain. There were several adverse events: some were the expected opioid adverse effects such as nausea, constipation and vomiting; others were not typical opioid adverse effects (for example, decreased appetite, dizziness and pyrexia, as shown in Table 1 in the main review), but generally showed no difference between groups. There were three deaths in the morphine group during the trial period, considered to be due to disease progression and unrelated to the drug. Three trials had over 10% dropout, but the reason and proportion of dropout was balanced between groups. The overall quality of evidence was very low mainly due to high risk of bias, imprecision of effect estimates and publication bias. There were no data available for children or for several participant-important outcomes, including participant-reported pain relief and treatment impact on consciousness, appetite or thirst.
AUTHORS' CONCLUSIONS
This review indicated little difference between hydromorphone and other opioids in terms of analgesic efficacy. Data gathered in this review showed that hydromorphone had a similar effect on participant-reported pain intensity as reported for oxycodone and morphine. Participants generally achieved no worse than mild pain after taking hydromorphone, which is comparable with the other drugs. It produced a consistent analgesic effect through the night and could be considered for use in people with cancer pain experiencing sleep disturbance. However, the overall quality of evidence was very low mainly due to risk of bias, imprecision of effect estimates and publication bias. This review only included four studies with limited sample size and a range of study designs. Data for some important outcomes, such as impact of the treatment on consciousness, appetite or thirst, were not available. Therefore, we were unable to demonstrate superiority or inferiority of hydromorphone in comparison with other analgesics for these outcomes. We recommend that further research with larger sample sizes and more comprehensive outcome data collection is required.
Topics: Adult; Analgesics, Opioid; Female; Humans; Hydromorphone; Male; Morphine; Neoplasms; Oxycodone; Pain; Pain Measurement; Randomized Controlled Trials as Topic
PubMed: 27727452
DOI: 10.1002/14651858.CD011108.pub2