Palliative Medicine and Pain Unit

Location: Royal Marsden

Section: NHS Clinical Research Programme

Head of Services: Dr Julia Riley

Introduction

Pain is one of the commonest, and often most feared, symptoms in patients with cancer. We provide care for patients at all stages of their disease by means of an out-patient service, an in-patient support team and an in-patient specialist unit. 

Cancer and pain

Ongoing or progressive pain is physically debilitating and has a marked impact on quality of life. Since a third of the population will die from cancer, and of these 80% will experience severe pain in their final year of life, effective treatment of cancer-related pain remains a high priority and an ongoing challenge in clinical practice. Individuals with moderate to severe cancer-related pain require treatment with strong analgesics, namely opioids.

An important advance in promoting the principles of good pain control for cancer patients worldwide was the publication of the World Health Organisation (WHO) analgesic ladder. This sought to simplify pain management strategies and promote a universal step-wise increase in the potency of analgesics prescribed.

Whilst morphine is the opioid of choice for the treatment of moderate to severe cancer pain, approximately 25% of patients treated with oral morphine do not have successful outcomes either because of intolerable adverse effects, inadequate analgesia or a combination of both.

Our team has focused on research into pain, looking at the different inter-individual variations of patient responses to morphine. This includes investigations into variations in individual genetics, immunology, metabonomics and proteomics.

We aim to develop a model that will predetermine which patients respond to which opioids. This will enable us to tailor the prescribing of opioids to the needs of each individual patient.

A new infrastructure for research in palliative care

The Department of Pain and Medicine at the Royal Marsden is a multidisciplinary team made up of specialist doctors and nurses, and a number of other relevant healthcare professionals including a physiotherapist, occupational therapist, social worker and dietitian. One of the biggest hurdles in supporting research in a new field is establishing an infrastructure. We have developed an infrastructure that now supports research nurses, doctors and scientists doing postgraduate degrees. Dr Joy Ross became the first person to be awarded her PhD in Palliative Medicine at the Royal Marsden in 2006. Maureen Carruthers is a Clinical Nurse Specialist with an interest in lung cancer; she completed an MSc in Advanced Practice in 2006. Dr Sophy Gretton and Dr Joanne Droney are the two current PhD fellows. Anna-Marie Stevens, Clinical Nurse Specialist, has been involved in research into the effects of nurse prescribing in palliative care, outcome measures for palliative care, and end of life assessments.

We have also developed international collaborations with basic scientists, other clinical specialists, and allied health professionals with a track record of research in this field. Our collaborators include Imperial College, the University of Oxford, the University of Manchester, University Medical School at Yale (USA), University of The Norwegian University of Science and Technology (Norway) and Aalborg University (Denmark).

Palliative care database

The Department established and maintains a palliative care database which contains data on over 400 patients collected over 4 years. The database comprises over 1,000 fields including cancer type, treatment modalities, morphine responsiveness, side effect profiles, basic and research immunology profiles such as flow cytometry cell subsets, biochemistry data, and genetic data. The genetic data field includes information on genes involved in the pharmacology of opioids as well as those genes which, from knockout, array and other literature sources, indicate potential association with either pain or its side effects. An important strength of this database is its pain and side effect perception scores and the metabolic data relating to the drug pharmacogenetics. DNA, serum and cells are stored in this collection of over 45 documented tumour groupings but only host genetics are recorded. Additional data is available on limited patient subsets of metabonomic and proteomic data.

The database has a dual entry system, where at least one entrant is a clinician, and is subject to rigorous iterative audit using sophisticated data mining techniques. With few exceptions, for example newer studies involving metabonomics, proteomics, constipation and orgomics, missing data are regarded as an error. The Chief Clinical Officer to the NHS Information Technology strategy, Dr Michael Thick, is a visiting professor at Imperial College where the database is held and he maintains an active interest in it.

Pain and functional magnetic resonance imaging

Dr Sophy Gretton from our Department has been working jointly with the Centre for Functional Magnetic Resonance Imaging of the Brain (Oxford) on the effect of opioids on the brain. Dr Joanne Droney is working in collaboration with the gastrointestinal group from the University of Manchester and the Royal London Hospital on opioid-induced constipation.

The pain plate

Dr Julia Riley and Dr Joy Ross are involved in projects looking at the reasons why 10-30% of patients at the Royal Marsden Hospital are reported to have an unsuccessful outcome when prescribed oral morphine. These projects include investigation into the genetic, immunological and metabolic reasons for the poor response to morphine; preliminary data are encouraging. Dr Riley’s team, working in collaboration with Professor Kenneth Welsh at Imperial College, have developed a pain plate. This tool, which is being continuously expanded, determines polymorphisms in genes that are thought important to pain, drug side effects and relevant pharmacogenomics.

Breakthrough pain

Many people with chronic cancer-related pain experience intermittent flares of severe pain that can occur even though analgesic medication is being taken regularly; these flares of pain are called breakthrough pain. Dr Andrew Davies from our Department has set up a new project for 2007 which aims to develop a validated clinical tool for the routine assessment of breakthrough pain. Other relevant projects in this area include clinical trials of intranasal and sublingual opioid sprays in the management of breakthrough pain.

Oral care in patients with advanced cancer

Dr Davies also has an interest in the management of oral problems in patients with advanced cancer; his research collaborators include the GKT Dental Institute at King’s College and the Dental School at the University of Glasgow. He is undertaking research for the Department of Health into antifungal drug resistance amongst oral yeasts and investigating new strategies for treating oral candidosis such as salivary stimulants and tea tree oil. The antifungal resistance studies were the first palliative care studies to be adopted by the National Cancer Research Network.

The latest study on the use of salivary stimulants to treat oral candidosis was rated as an alpha star project by The Institute and Royal Marsden’s joint Committee for Clinical Research.

Dyspnoea and cancer

Dr Anne Louise Jennings has a long-term interest in the use of opioids to manage dyspnoea (shortness of breath) in patients with malignant and non-malignant disease. She is currently involved in updating the Cochrane Collaboration systematic review on dyspnoea in all patients, and is also leading a Task Group for the Association of Palliative Medicine of Great Britain and Ireland to develop evidence - based on guidelines on the management of dyspnoea in malignant disease.

Acute pain

Acute pain management in cancer patients and use of intrathecal infusions is one of the main research interests of Dr John Williams who is a member of the British Pain Society Cancer Pain Committee. He is involved in a number of projects in this area including:

• A study looking at the analgesic effect and side effects of different opioids in post-operative pain
• A national survey of UK intrathecal pump usage which will be used to produce British Pain Society guidelines on intrathecal pump use
• The NHS Health Technology Assessment Program (CEAN): a collaborative project with Brunel University that is evaluating the efficacy and cost efficiency of drugs used to treat neuropathic pain

Additionally, The Royal Marsden Hospital Charitable Trust fund are funding a project entitled ‘Towards a Pain Free Hospital’ which will assess and compare the incidence of unrelieved cancer-related pain in oncology out-patients at the Royal Marsden Hospital with other centres in the UK and abroad. The effectiveness of pain clinic treatment given to these patients will also be measured.

The project is scheduled to start with Head and Neck oncology out-patients and then rotate through all clinical units within the hospital.

Dr Williams is also the lead medical advisor on a collaborative educational project on pain management with The Institute's Interactive Education Unit. The project, scheduled for launch in August 2007, will result in the production of an educational CD ROM aimed at healthcare professionals who treat patients with cancer-related pain.

Neuropathic pain, specifically pain in cancer survivors and chemotherapy-induced nerve pain, is one of the research interests of Dr Paul Farquhar-Smith. He is involved in the formulation of British Pain Society (BPS) guidelines for pain in cancer survivors and is also working on the CEAN project with Dr Williams.

The future

In addition to providing clinical care for patients within The Royal Marsden NHS Foundation Trust, the Department runs an extensive research programme. Pipeline funded projects for completion in 2007 include:

• 150 patient samples together with 300 controls will be run through the new Illumina 400,000 SNP chip in collaboration with Dr Josephine Hoh at Yale University (USA)
• Additional proteomic, metabonomic and orgomic data will also be collected on these samples in collaboration with Somalogic (Denver, USA), Imperial College and IBIS technologies (Carlsbad, USA). Complex SNPs, for example COMT, CYP2D6, 3A4 and others NOT amenable to chip technology, will be covered by our in-house pain plate which uses more sophisticated assay technology