Opioid doses and the survival of advanced cancer patients receiving palliative care

Sathornviriyapong, A. et al. BMC Palliative Care. Published online: 21 November 2016

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Image source: Adrian Wressell, Heart of England NHSFT – Wellcome Images // CC BY-NC-ND 4.0

Background: Concerns that opioids may hasten death can be a cause of the physicians’ reluctance to prescribe opioids, leading to inadequate symptom palliation. Our aim was to find if there was an association between different opioid doses and the survival of the cancer patients that participated in our palliative care program.

Conclusions: Our study has demonstrated that different opioid doses in advanced cancer patients are not associated with shortened survival period.

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Breakthrough cancer pain: twenty-five years of study

Mercadante, S. & Portenoy, R. K. (2016) Pain157(12) pp. 2657–2663

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Breakthrough cancer pain (BTcP) is an episode of severe pain that “breaks through” a period of persistent pain at least partly controlled by a stable opioid regimen. Although mentioned in the literature decades ago, it has been only 25 years since the first effort to define and measure it.

Controversy about the definition of BTcP continues despite an international effort to achieve consensus. Nevertheless, common approaches to measurement of BTcP have led to a robust literature, including many surveys that have described prevalence, characteristics, and association with adverse outcomes. Measurement also has been important for clinical trials of new drug formulations specifically designed for BTcP. Several approaches have been reported in the literature, although most of them have never been substantiated with appropriate studies. Administration of an opioid as needed is the most common treatment.

Twenty-five years of research has produced a more refined understanding of the safety and efficacy of oral opioids in this context, and provided the clinical trials data necessary to attain regulatory approval of multiple new formulations specifically developed for BTcP. Transmucosal formulations of fentanyl may provide meaningful analgesia within 5 to 15 minutes. Given the difference in cost, transmucosal formulations should be considered in a subset of patients with BTcP, including those with pain that are not adequately controlled with an oral drug and those with distress associated with the rapid pain onset. The long-term use of opioids for BTcP remains to be clarified. Future studies should assess the potential of personalized treatment of BTcP.

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Cancer patients not getting adequate pain relief

Many terminal cancer patients are not getting adequate pain relief early enough, according to an English study.| Science Daily | PAIN

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Many terminal cancer patients are not getting adequate pain relief early enough, according to a University of Leeds study.  The researchers found that, on average, terminal cancer patients were given their first dose of a strong opioid such as morphine just nine weeks before their death.  Yet many people with terminal cancer suffer with pain a long time before that, the researchers said.

The research team used UK Cancer Registry data to study a sample of 6,080 patients who died of the disease between 2005 and 2012. They found that 48 per cent of the patients were issued a prescription in general practice (primary care) for a strong opioid medication, such as morphine, during the last year of their life.

The study, published in the medical journal Pain, said efforts to improve treatment of cancer pain may be being hindered by concern over the ongoing ‘opioid epidemic’.

They cited NHS data which showed that overall opioid prescribing increased by 466 per cent between 2000 and 2010, but only increased by 16 per cent for patients with cancer.

Full reference: Lucy Ziegler et. al. Opioid prescribing for patients with cancer in the last year of life. PAIN, Published Ahead of Print 2016

Vitamin D and patients with palliative cancer

Björkhem-Bergman, L. & Bergman, P. (2016) BMJ Supportive & Palliative Care. 6:287-291

dandelion-1557110_960_720Vitamin D is a hormone that is synthesised in the skin in the presence of sunlight. Sufficient vitamin D levels are important—not only for a healthy skeleton—but also for a healthy immune system. Many patients with cancer have insufficient vitamin D levels, and low vitamin D levels are associated with increased ‘all-cause mortality’ and especially mortality due to cancer. Low vitamin D levels have also been associated with increased risk of infections, increased pain, depressive disorders and impaired quality of life.

We review the role of vitamin D in the immune system, in relation to cancer disease, pain and depression. We have recently performed an observational study in 100 patients with palliative cancer in Sweden. The main result was that low vitamin D levels were associated with higher opioid dose, that is, more pain. We also describe a case report where vitamin D supplementation resulted in radically decreased opioid dose, less pain and better well-being.

Vitamin D supplementation is not connected with any adverse side effects and is easy to administrate. Thus, we hypothesise that vitamin D-supplementation to patients with palliative cancer might be beneficial and could improve their well-being, decrease pain and reduce susceptibility to infections. However, more clinical studies in this field are needed before firm conclusions can be drawn.

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Study shows patients require less painkilling medication after breast-cancer surgery if they have opiate-free anesthesia

ScienceDaily. Published online: 30 May 2016.

Image shows Remifentanil’s 3D molecular structure

In this study, painkiller requirements were examined after patients received opiate anaesthesia and non-opiate anaesthesia. A randomised controlled trial was conducted, containing two groups each containing 33 breast cancer patients undergoing a mastectomy or lumpectomy. The study took place between September 2014 and July 2015 at the Jules Bordet Institute, Brussels.

Perioperative non-opiate analgesia was obtained by combining clonidine (0.2 mcg/kg), ketamine (0.3 mg/kg) and lidocaine (1.5 mg/kg). An extra bolus of ketamine (0.2mg/kg) was given if necessary. Opiate analgesia was obtained via a combination of remifentanil infusion, ketamine (0.3 mg/kg) and lidocaine (1.5 mg/kg). Both groups received intravenous paracetamol (1000mg/6h) and intravenous diclofenac (75 mg/12h). Patients received a PCA (patient-controlled analgesia) pump for breakthrough pain during the first 24 hours post-operatively.

Clinical characteristics and post-operative piritramide painkiller consumption (through the patient controlled pump) were assessed during the first 24 hours post-operatively. Data were not complete for two patients in the non-opiate group, and thus a total of 64 patients were included in the study. The total mean piritramide usage 24 hours post-operatively was 8.1 mg (range 2.0-14.5) in the non-opiate group and 13.1 mg (range 6.0-16.0) in the opioid group. The difference observed was statistically significant.

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Randomized Trial of Low-Dose Morphine Versus Weak Opioids in Moderate Cancer Pain

Bandieri, E. et al. JCO February 10, 2016 vol. 34, no. 5 436-442

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Image source: Eric Norris

Purpose: The WHO guidelines on cancer pain management recommend a sequential three-step analgesic ladder. However, conclusive data are lacking as to whether moderate pain should be treated with either step II weak opioids or low-dose step III strong opioids.

Patients and Methods: In a multicenter, 28-day, open-label randomized controlled study, adults with moderate cancer pain were assigned to receive either a weak opioid or low-dose morphine. The primary outcome was the number of responder patients, defined as patients with a 20% reduction in pain intensity on the numerical rating scale.

Results: A total of 240 patients with cancer (118 in the low-dose morphine and 122 in the weak-opioid group) were included in the study. The primary outcome occurred in 88.2% of the low-dose morphine and in 57.7% of the weak-opioid group (odds risk, 6.18; 95% CI, 3.12 to 12.24; P < .001). The percentage of responder patients was higher in the low-dose morphine group, as early as at 1 week. Clinically meaningful (≥ 30%) and highly meaningful (≥ 50%) pain reduction from baseline was significantly higher in the low-dose morphine group (P < .001). A change in the assigned treatment occurred more frequently in the weak-opioid group, because of inadequate analgesia. The general condition of patients, which was based on the Edmonton Symptom Assessment System overall symptom score, was better in the morphine group. Adverse effects were similar in both groups.

Conclusion: In patients with cancer and moderate pain, low-dose morphine reduced pain intensity significantly compared with weak opioids, with a similarly good tolerability and an earlier effect.

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The effectiveness of buprenorphine for treating cancer pain: an abridged Cochrane review

Mia Schmidt-Hansen et al. BMJ Supportive & Palliative Care. Published Online: 15 December 2015

Objectives To assess the effectiveness and tolerability of buprenorphine for cancer pain in adults and children.

Methods We searched CENTRAL, MEDLINE, EMBASE, ISI Web of Science, ISI BIOSIS, ClinicalTrials.gov, metaRegister of Controlled Trials, WHO International Clinical Trials Registry Platform and the Proceedings of the Congress of the European Federation of International Association for the Study of Pain to early 2015.

Results We included 19 randomised controlled trials comparing buprenorphine with placebo, buprenorphine or another active drug for cancer pain. The trials included 1421 patients and examined 16 different intervention comparisons. Of the 11 studies that compared buprenorphine to another drug, 5, 3 and 3 studies, respectively, found that buprenorphine was superior, no different or inferior to the alternative treatment in side effects profile or patient preference/acceptability. Pain intensity ratings did not differ significantly between intramuscular buprenorphine and buprenorphine suppository, although intramuscular treatment was associated with more adverse events (1 study). One study found faster onset of pain relief after sublingual than subdermal buprenorphine, with similar analgesia duration and adverse event rates. 2 studies found transdermal buprenorphine superior to placebo, whereas a third study found no difference between placebo and different doses of transdermal buprenorphine. No clear dose–response relationship was found for transdermal buprenorphine. The quality of this evidence base was limited by under-reporting, small sample sizes and attrition.

Conclusions Buprenorphine might be considered as a fourth-line option compared with the more standard therapies of morphine, oxycodone and fentanyl, and even then it would only be suitable for some patients.