Hydromorphone for cancer pain New

Abstract

Abstract 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.

Author(s)

Yan J Bao, Wei Hou, Xiang Y Kong, Liping Yang, Jun Xia, Bao J Hua, Roger Knaggs

Abstract

Plain language summary

Hydromorphone for the treatment of cancer pain

Background

Over 75% of people with cancer experience pain. Around 30% to 50% of these people have moderate to severe pain, which can have a negative impact on daily life. Cancer pain is a distressing symptom that tends to worsen as the disease progresses. Hydromorphone may help relieve these symptoms.

Cancer‐related pain is usually treated with medicines such as morphine, oxycodone, fentanyl or hydromorphone. This review looked at how effective hydromorphone was in relieving symptoms of moderate to severe cancer pain.

Results

In April 2016, we searched for clinical trials looking at hydromorphone in people with moderate to severe cancer pain. We found four small, but well conducted, studies with 604 adults (none of the studies included children) comparing hydromorphone with oxycodone or morphine.

Based on very low quality evidence, we found no differences between the treatment groups relating to pain intensity and most people had good pain relief. Hydromorphone seemed to work as well as morphine and oxycodone. There were some side effects, such as confusion, constipation and diarrhoea, but generally there was no difference between people taking hydromorphone and people taking morphine or oxycodone.

Conclusions

The studies did not provide enough high quality evidence to draw conclusions from; however, based on very low quality evidence, hydromorphone seemed to work as well as morphine and oxycodone and had similar side effects. Hydromorphone provided consistent pain relief through the night and could be considered for use in people with cancer who find it difficult to sleep due to the pain.

Author(s)

Yan J Bao, Wei Hou, Xiang Y Kong, Liping Yang, Jun Xia, Bao J Hua, Roger Knaggs

Reviewer's Conclusions

Authors' conclusions

Implications for practice For people with cancer pain

Based on data gathered from the four included trials, it appears that hydromorphone has a similar effect on participant‐reported pain intensity as oxycodone and morphine for adults with moderate to severe cancer pain. There was no evident comparative difference in analgesic effect between hydromorphone and other opioids investigated in this review and, on average, participants achieved no worse than mild pain on all investigated treatments. There were several adverse events, but generally there was no difference between groups. In summary, the evidence suggests that hydromorphone has a similar therapeutic effect and adverse effects to oxycodone and morphine in adults with moderate to severe chronic cancer pain. However, this finding should be applied with caution for it only included four studies with different designs and limited sample size. There were no data available for children or for some important outcomes such as impact of the treatment on consciousness, appetite and thirst.

For clinicians

Based on four included trials with different designs and limited number of participants, we found a lack of evidence to support a preference for hydromorphone over other opioid analgesics such as morphine and oxycodone. The treatment effect of hydromorphone appeared to be similar to that of the comparator drugs for adults with moderate to severe cancer pain. There were minor adverse events in all treatment groups and generally no significant difference between groups. However, most of the outcome data were based on single randomised controlled trials with small sample size, thus the findings of the current review should be interpreted and applied with caution. We found no data for children. The insufficient evidence requires clinicians to balance potential benefits against potential adverse events on the merit of each individual case when recommending treatment in clinical practice.

For policy makers

This review identified little evidence to support hydromorphone as the first‐, second‐ or third‐line treatment for cancer pain. However, evidence collated in the current review suggests hydromorphone has a similar analgesic effect as morphine and oxycodone, it can be considered as an alternative when other opioids result in excessive adverse events such as sedation and respiratory depression, and when people with cancer pain experience renal failure. We found no data for children. Included studies were conducted in high‐income countries, which may compromise the external validity of the review as some of the drugs investigated may have limited accessibility in some lower‐income countries. Finally, it is worth noting that findings from the current review are mainly based on small trials with different designs and limited sample size and some risk of bias, therefore, should be applied with caution.

Implications for research

This review reveals a general lack of research in this subject area. Future trials with significant numbers of participants (e.g. over 200 per treatment arm) are needed to evaluate the safety and effectiveness of hydromorphone for the management of moderate to severe cancer pain in adults. Future research is encouraged to involve children and young adults to provide direct evidence in this population. Further adequately powered randomised controlled trials should use standardised tools or scales to measure pain as a primary outcome. More data on other secondary outcomes, as well as the comparative effect of a more comprehensive range of medications, would also be useful to enable the review to draw a more reliable and conclusive effect. Longer‐term toxicity data should be collected if possible.

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