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Hydromorphone for cancer pain. 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.

Hydromorphone for cancer pain. 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.