Nausea remains a significant problem for patients towards the end of life, regardless of the illness they have. There are a variety of drugs to treat nausea (antiemetics) available, but very little research to show which are most effective.
Key points:
- This is the first study to examine real-world use of cyclizine in palliative care.
- Approximately ¾ or patients benefit from cyclizine.
- Around ⅓ of patients have tolerable side effects from cyclizine.
- This is similar to other antiemetics in palliative care.
Choosing the right antiemetic
In many cases in medicine, clinical trials directly compare two different treatments to clearly demonstrate an advantage of one over the other. Unfortunately, no such trials exist for antiemetics – medications used to prevent or relieve nausea - in palliative care. So how do clinicians decide which of the many antiemetics are best for the patient in front of them?
A traditional method has been to choose based on the suspected cause of the nausea. There are theoretical reasons why some antiemetics might work better for some kinds of nausea than others. The problem is, this really is only theoretical. A trial conducted by the Palliative Care Clinical Studies Collaborative (PaCCSC) in 2018 showed no real difference in benefit between this approach and giving everyone the antiemetic haloperidol.
In contemporary practice, many clinicians instead choose the antiemetic they perceive will cause the least side-effects. However, while the side-effects of most drugs are known at point of registration, which ones occur for individual patients depends on other factors such as what medical conditions they have, how sick they are, and which other drugs they are taking. This highlights another gap in palliative care research – the lack of good quality data on what side-effects patients in palliative care get from the same drugs used in other settings.
Pharmacovigilance in palliative care
Randomised controlled clinical trials are the best way of demonstrating one treatment is better than another. However, they are costly, and usually use a fixed dose of a drug in a narrow population. They aren’t good for understanding the effect of a drug in real-world patients. For this, we need prospective, observational studies – pharmacovigilance studies.
The IMPACCT Rapid Program has 52 series - 42 adult and 10 paediatric - that have collected or are currently collecting data about interventions in palliative care to understand both how well they work and what harm they do in the real world. These complement, rather than replace, randomised clinical trials.
Cyclizine and nausea
Cyclizine is one of the antiemetics available in Australia and around the world. Clinicians often worry about the side effects, and this is one reason it isn’t used first line for nausea in palliative care. However, there are no studies of patients in palliative care to understand the side-effect profile. We have now completed Rapid Program Series 12, Cyclizine for nausea.
This series assessed 101 patients across 19 sites in Australia, New Zealand, and the UK. It showed that around three quarters of patients experienced benefit and around one third experienced harm. What’s interesting is that this is similar to other antiemetics used in palliative care. This means that clinicians may be seeing cyclizine as more harmful than it actually is, and that cyclizine remains a good option for selected patients in palliative care.
More studies are needed to directly compare different antiemetics, and to observe patients on treatment for longer.
The results of this trial are being presented pre-publication in the upcoming NSW Cancer Conference and will be published later this year.
Dr Richard McNeill is a palliative care physician and clinical pharmacologist in New Zealand. He is currently employed at Nurse Maude Hospice in Christchurch, and he is also a research fellow at the University of Otago. He is undertaking a masters in clinical informatics. Richard has an interest in research involving all aspects of pharmacotherapy in palliative care.