Elizabeth Rees

What influences participation in clinical trials in palliative care in a cancer centre

Like any other specialty, palliative care needs a scientific foundation on which to base its practice. Research in palliative care is particularly difficult because of the characteristics of the patient population under study (e.g. advanced disease, poor performance status and limited prognosis). The aim of this paper was to highlight the challenges of recruitment into clinical trials in palliative care. Information on all patients treated at a specialist cancer centre who were referred for consideration of entry into any one of 23 clinical trials in palliative care was collected prospectively over 4 years to determine factors that influence patients to accept or reject entry into a study. Of the 1206 patients referred, 558 (46%) met the entry criteria. Of these, 362 (30%) agreed to enter and 248 (21% of all those referred) completed the study. Thus, 65% of all eligible patients were entered into trials but only 44% of these completed the study. The relatively high percentage of patients entered probably reflects the site (a cancer centre with a high research profile) and is not typical of other palliative care centres or hospices. The most common reasons given for unwillingness to participate were a wish to defer to a later date, a deterioration in condition, distance from home to hospital, a lack of interest, transfer to another unit, inability to give consent and family objection. In order to maximise patient accrual into trials in palliative care, studies should be designed to suit the patient population under study (e.g. be of short duration with realistic entry criteria) and not necessarily mirror the trial methodology of therapeutic trials in oncology.

A prospective survey of the use of dexamethasone on a palliative care unit

One hundred and six consecutive patients started on glucocorticosteroids (steroids) according to a defined prescription policy were surveyed each week to document the indications for use, any beneficial effect, any toxicity incurred and the reason for stopping. All patients had advanced malignant disease and survived for a median of 40.5 days (range 1–398+ days) from the start of steroid treatment. Fifty-seven per cent of patients completed three or more assessments. The most common specific indications for starting steroids were spinal cord compression, cerebral metastases, lymphangitis carcinomatosa and intestinal obstruction. The most common non-specific indications were anorexia, nausea, low mood, pain and vomiting. The median duration of steroid use was 21.5 days (range 1–89 days). The most common reason for the discontinuation of steroids was death or deteriorating condition. Symptom scores improved at some stage for the majority of patients started on steroids for anorexia, nausea, pain, low mood, vomiting and weakness but not in patients complaining of dyspnoea or poor mobility. The most common side-effects that were most probably attributable to steroid therapy were oral candidosis and proximal myopathy. The benefits of steroids when used according to defined guidelines were thought to outweigh toxicity.

The use of the Edmonton Symptom Assessment Scale (ESAS) within a palliative care unit in the UK

The Edmonton Symptom Assessment scale (ESAS) was used on 1004 occasions to assess 71 patients with advanced malignant disease admitted to a palliative care unit in the UK over a six-week period. The median length of inpatient stay was eight days (range 1–36) and the median survival from start of ESAS to death was 16 days (range 2–202). Across all patients there was a trend towards worsening symptom scores over the first five days from admission with a significant deterioration in appetite scores. When scores were analysed retrospectively over five days according to outcome (death–group 1, or discharge–group 2) there was a significant improvement in pain scores in group 2 but no change in overall score, and a significant deterioration in activity, drowsiness and appetite in group 1 with no change in overall score. ESAS did not seem an appropriate tool in this group of patients as the total symptom scores were so often biased by the inevitable increase in individual symptom scores immediately prior to death.

A Phase II Study to Establish the Efficacy and Toxicity of Sodium Valproate in Patients With Cancer-Related Neuropathic Pain

The efficacy and toxicity of sodium valproate for cancer-related neuropathic pain was evaluated in a phase II study at this cancer center. Twenty-five patients entered the study over a 13 month period. Pain was assessed using a pain scale based on the Brief Pain Inventory at days 0, 8 and 15. Nineteen patients completed the two week study period, one patient discontinued treatment because of toxicity, and five discontinued because of progressive disease. The most frequently observed side effects were drowsiness, unsteadiness, nausea, and decreased appetite. Response was defined as a decrease in pain score in the absence of increased need for analgesic medication. The response rate for average pain at day 15 in assessable patients was 55.6% (30.8-78.5%, 95% CI), but response rates varied considerably depending on the mode of analysis. Baseline efficacy data have been gained on which to base future comparative studies against antidepressants.

Novel consent process for research in dying patients unable to give consent.

Abstract Objectives To develop a process of advance consent to enable research to be undertaken in patients in the terminal phase. Design Feasibility study of an advance consent process to support a randomised controlled trial of two antimuscarinic drugs (hyoscine hydrobromide and glycopyrronium bromide) in the management of noisy respirations associated with retained secretions (“death rattle”). Setting Palliative care wards in a major cancer centre. Participants Patients admitted to a palliative care ward who may develop “death rattle” and thus be eligible for randomisation. Main outcome measures Patient accrual; acceptability of the consent process. Results Of the 107 patients approached, 58 patients gave advance consent to participate in the study. Of these, 15 patients developed death rattle and were randomised to receive either hyoscine or glycopyrronium; 16 patients died elsewhere; 15 patients died on the palliative care wards but were not randomised; 12 patients are still alive. Conclusions Initial assessment suggests that this is a workable consent process allowing research to be undertaken in patients who are unable to give consent at the time of randomisation. Patient accrual rates to date are lower than needed to recruit adequate numbers in the time allotted to answer the research question.

The use of the Rotterdam symptom checklist in palliative care

The Rotterdam Symptom Checklist (RSCL), which measures both physical and psychological aspects of quality of life (QOL), was given to all new patients admitted to a palliative care unit who were thought capable of filling out a questionnaire as an outcome measure of symptom control. Assessments were obtained from 52 patients at baseline (week 1). This represented only 53% of the new patients admitted to the unit. Thirty-one patients completed a second questionnaire at week 2, and only 28 patients completed a third (week 3). In these selected patients, the median overall RSCL scores were 57, 52, and 49 at weeks 1, 2, and 3. There was a significant improvement in QOL scores across the three measurements with a significant difference between weeks 1 and 3 (P = 0.05) but not between weeks 1 and 2. Primarily because of the inability of many patients to complete the questionnaire and the high attrition rate, the appropriateness of this tool as a symptom control measure in palliative care patients is questioned.

An assessment of the efficacy and tolerability of a 'double dose' of normal-release morphine sulphate at bedtime.

This study was a prospective, randomized, open, crossover study comparing a double dose (DD) of normal-release (NR) morphine at bedtime with a single dose (SD) of NR morphine at bedtime and 4 h later. Twenty patients completed the study. Four patients required breakthrough analgesia during the SD phase of the study, whilst 11 patients required breakthrough analgesia during the DD phase of the study (P=0.016). Moreover, all of the pain scores were worse during the DD phase (overnight pain, P <0.01; morning pain, P<0.01), and some of the opioid-related side effect scores were worse during the DD phase (xerostomia, P=0.033; vivid dreams, P=0.05). This study does not support the European Association for Palliative Care (EAPC) recommendations on the use of a double dose of NR morphine at bedtime.

End of life care in patients with malignant disease

Most cancer patients die in hospital [1]. The care of terminally ill patients often falls to junior doctors or nurses who will have had little specific training in the care of the dying. Relatively few dying patients will ever be seen by a member of a specialist palliative care team. If the management of the terminal phase is poor, it can be a source of great distress for patients (who may suffer unnecessary discomfort), for their families (who may have more difficulty in coming to terms with their bereavement) and for healthcare professionals (who may feel that they have failed in their duty of care). Expertise in caring for dying patients has developed in hospices and specialist palliative care teams. Strong evidence for the effectiveness of this approach (in the form of randomised controlled trials) is generally not available. It is difficult to undertake research in palliative care. Studies are hindered by the poor performance status and the changing nature of symptoms in patients with advanced malignant disease, high attrition rates and difficulties inherent in obtaining consent for trials in terminally ill patients [2,3]. A recent systematic review concluded that specialist palliative care teams can improve the outcome of cancer patients [4]. Moreover, clinical experience suggests that the widespread adoption of a multidisciplinary palliative care approach would improve the care of patients dying outside specialist palliative care units. This paper provides a review of current ‘best practice’ in the management of the terminal phase. 2. General approach

Is there a dose response relationship for clodronate in the treatment of tumour induced hypercalcaemia

Eighty-six patients with tumour induced hypercalcaemia were randomised to 600, 900, 1200 or 1500 mg of intravenous clodronate, according to post hydration serum calcium levels. Sixty-seven were evaluable for response. The overall response rate was 49.3% (95% CI: 36.8–61.8) with no significant difference in response rates, i.e. achievement of normocalcaemia at days 6–9 (corrected serum calcium ⩽2.6 mmol l−1) across all groups.