Cancer patients not getting adequate pain relief

Many terminal cancer patients are not getting adequate pain relief early enough, according to an English 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.

Researchers at Leeds University 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.

We have identified for the first time the relatively late onset and short duration of strong opioid treatment in cancer patients prior to death,” said lead study author Dr Lucy Ziegler, a senior research fellow in palliative care at the University of Leeds.

This pattern of prescribing does not match population data which points to earlier onset of pain. Nine weeks before death is considered late in the course of the cancer trajectory. Although the prevalence of pain is higher in patients with advanced cancer and towards the end of life, for many patients pain is experienced at many stages throughout the illness. In fact, pain is the most common presenting symptom at diagnosis. Our research highlights the need to prioritise earlier access to effective pain management for patients with advanced cancer.”

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 analysed the anonymised corresponding primary care medical records of the patients to find out their prescription history. 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 median interval between first prescription and death was nine weeks.

We examined whether late diagnosis could account for this, but median survival for our sample from diagnosis was 60 weeks, suggesting that most opioid prescribing in fact occurred late in the trajectory between diagnosis and death, regardless of cancer duration,” said Mike Bennett, a professor of palliative medicine at the University of Leeds, who co-authored the research.

In addition, over 90 per cent of all patients in the cohort had received some form of cancer treatment, therefore it was not the absence of a cancer diagnosis or poor engagement with cancer services that hindered timely access to an opioid.

The study found that over-60s were more likely to be prescribed drugs late than younger people, while those who died in a hospice (rather than in hospital, at home or in a care home) were more likely to have been prescribed drugs earlier. The research team, whose study is 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. Although the University of Leeds researchers did not examine pain severity, previous studies have found that up to 86 per cent of patients with advanced cancer will experience pain.

Within the advanced cancer population there is a need to develop mechanisms to improve pain assessment and initiate a more proactive approach to prescribing, particularly for older patients,” said Dr Ziegler.

Effective pain control is fundamental to good quality of life. For patients who are approaching the end of their lives it is crucially important we strive to get this right and that we help them achieve the best quality of life possible. One mechanism to achieve this may be through earlier integration of specialist palliative care and we are exploring in a related study funded by Yorkshire Cancer Research whether contact with palliative care services improves access to opioids.”

Ziegler et al. Opioid prescribing for patients with cancer in the last year of life. PAIN, 2016; 1 DOI:10.1097/j.pain.0000000000000656 [Abstract]

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How Chinese medicine kills cancer cells

Researchers at the University of Adelaide have shown how a complex mix of plant compounds derived from ancient clinical practice in China – a Traditional Chinese Medicine – works to kill cancer cells.

Compound kushen injection (CKI) is approved for use in China to treat various cancer tumours, usually as an adjunct to western chemotherapy – but how it works has not been known. This study, published in the journal Oncotarget, is one of the first to characterise the molecular action of a Traditional Chinese Medicine rather than breaking it down to its constituent parts.

Most Traditional Chinese Medicine are based on hundreds or thousands of years of experience with their use in China,” says study leader, Professor David Adelson, Director of the Zhendong Australia – China Centre for the Molecular Basis of Traditional Chinese Medicine.

“There is often plenty of evidence that these medicines have a therapeutic benefit, but there isn’t the understanding of how or why. If we broke down and tested the components of many Traditional Chinese Medicines, we would find that individual compounds don’t have much activity on their own. It’s the combination of compounds which can be effective, and potentially means few side-effects as well.”

This is one of the first studies to show the molecular mode of action of a complex mixture of plant-based compounds — in this case extracts from the roots of two medicinal herbs, Kushen and Baituling — by applying what’s known as a systems biology approach. This is a way of analysing complex biological systems that attempts to take into account all measurable aspects of the system rather than focussing on a single variable.”

The Zhendong Australia China Centre for Molecular Traditional Chinese Medicine was established at the University of Adelaide in 2012 in a collaboration with the China-based Shanxi College of Traditional Chinese Medicine and Zhendong Pharmaceutical Company. The Centre was established with a donation by the Zhendong Pharmaceutical Company, with the aim of understanding how Traditional Chinese Medicine works, and the long-term aim of possible integration into western medicineThe researchers used high-throughput next generation sequencing technologies to identify genes and biological pathways targeted by CKI when applied to breast cancer cells grown in the laboratory.

We showed that the patterns of gene expression triggered by CKI affect the same pathways as western chemotherapy but by acting on different genes in the same pathways,” says Professor Adelson.
These genes regulate the cell cycle of division and death, and it seems that CKI alters the way the cell cycle is regulated to push cancer cells down the cell death pathway, therefore killing the cells.”
Professor Adelson says this technique could be used to analyse the molecular mechanisms of other Traditional Chinese Medicines, potentially opening their way for use in western medicine.

Qu et al. Identification of candidate anti-cancer molecular mechanisms of compound kushen injection using functional genomics. Oncotarget,  2016; DOI:10.18632/oncotarget.11788 [Abstract]