End-of-life care in end-stage renal disease: renal and palliative care.

The numbers of patients with end-stage renal disease are growing, with a disproportionate increase among those who are elderly, dependent and with multiple co-morbidities. More of these patients are choosing to be managed conservatively, without dialysis. Palliative provision for these patients within UK renal services is limited, but the recent National Service Framework for Renal Services (Department of Health, 2005) has promoted service development. However, few models of service provision have been described. This article describes a retrospective review of a new service for conservatively-managed patients with end-stage renal disease. The range and complexity of the health needs of this population is demonstrated, and an example of service development described. A model of the stages of the conservative pathway and appropriate interventions was developed. The absence of research evidence prevented development of formal audit standards, and highlighted the urgent need for evaluation of models of care.

Systematic review of hypnotherapy for treating symptoms in terminally ill adult cancer patients.

The aim of this review was to find the evidence for or against the use of hypnotherapy in the treatment of symptoms in terminally ill adult cancer patients. The title and abstract were evaluated following a search through Index Medicus/MEDLINE, EMBASE, CINHAHL, CancerLit, AHMED, Psychinfo, CISCOM, Cochrane and DARE. Search terms included hypnotherapy, cancer, terminal care and palliative care. Inclusion criteria included systematic reviews, randomized controlled trials, observational and prospective studies, retrospective surveys, case studies and reports. A total of 27 papers were evaluated. Two reviewers assessed the studies, one extracted the relevant data and 10% were evaluated independently by a third reviewer. The 27 papers comprised a randomized controlled trial, an observational study, a retrospective questionnaire and 24 case studies. Hypnotherapy was used to treat a variety of symptoms, including pain, anxiety and depression. The poor quality of the studies and heterogeneity of the study population limited further evaluation; further research is required to understand the role of hypnotherapy in managing symptoms.

Systematic review of bisphosphonates for hypercalcaemia of malignancy.

BACKGROUND: Bisphosphonates are the treatment of choice for hypercalcaemia of malignancy (HCM) but there is no consensus regarding which drug or dose should be given. We designed a systematic review to investigate the efficacy of bisphosphonates in the treatment of HCM. METHODS: We identified randomized controlled trials (RCTs) by searching electronic databases, scanning of reference lists, and consultation with experts and pharmaceutical companies. Foreign papers were translated. Inclusion criteria were RCTs, confirmed malignant disease and measurement of serum calcium (ionized or corrected for albumin) postrehydration. The primary outcome was number of patients achieving normocalcaemia. Secondary outcomes were time to normocalcaemia, time to relapse and toxicity. RESULTS: Twenty-seven papers and two abstracts, using intravenous bisphosphonates, fulfilled the inclusion criteria. Data from 26 studies were used in analyses. Due to the heterogeneity of studies, meta-analysis could not be performed. Pamidronate was more effective than placebo, mithramycin, etidronate (7.5 mg/kg) and low-dose clodronate (600 mg), but equal to higher dose clodronate (1500 mg). Clodronate and etidronate were superior to placebo; incadronate was superior to elcatonin; gallium nitrate was superior to etidronate. No difference was seen between alendronate and clodronate. Three dose finding studies showed no difference between 30-90 mg of pamidronate, but one well designed study showed increasing efficacy with increasing dose. Studies using increasing doses of ibandronate (0.6-4 mg), alendronate (2.5-15 mg), and incadronate (2.5-10mg), showed a dose response. Duration of administration of pamidronate did not affect efficacy (six studies). CONCLUSION: Bisphosphonates normalize calcium in >70% patients with minimal side effects. Aminobisphosphonates are most effective at maintaining normocalcaemia and should be given in high dose irrespective of baseline serum calcium.

A systematic review of the role of bisphosphonates in metastatic disease.

OBJECTIVES: To identify evidence for the role of bisphosphonates in malignancy for the treatment of hypercalcaemia, prevention of skeletal morbidity and use in the adjuvant setting. To perform an economic review of current literature and model the cost effectiveness of bisphosphonates in the treatment of hypercalcaemia and prevention of skeletal morbidity. DATA SOURCES: Electronic databases (1966-June 2001). Cochrane register. Pharmaceutical companies. Experts in the field. Handsearching of abstracts and leading oncology journals (1999-2001). REVIEW METHODS: Two independent reviewers assessed studies for inclusion, according to predetermined criteria, and extracted relevant data. Overall event rates were pooled in a meta-analysis, odds ratios (OR) were given with 95% confidence intervals (CI). Where data could not be combined, studies were reported individually and proportions compared using chi-squared analysis. Cost and cost-effectiveness were assessed by a decision analytic model comparing different bisphosphonate regimens for the treatment of hypercalcaemia; Markov models were employed to evaluate the use of bisphosphonates to prevent skeletal-related events (SRE) in patients with breast cancer and multiple myeloma. RESULTS: For acute hypercalcaemia of malignancy, bisphosphonates normalised serum calcium in >70% of patients within 2-6 days. Pamidronate was more effective than control, etidronate, mithramycin and low-dose clodronate, but equal to high dose clodronate, in achieving normocalcaemia. Pamidronate prolongs (doubles) the median time to relapse compared with clodronate or etidronate. For prevention of skeletal morbidity, bisphosphonates compared with placebo, significantly reduced the OR for fractures (OR [95% CI], vertebral, 0.69 [0.57-0.84], non-vertebral, 0.65 [0.54-0.79], combined, 0.65 [0.55-0.78]) radiotherapy 0.67 [0.57-0.79] and hypercalcaemia 0.54 [0.36-0.81] but not orthopaedic surgery 0.70 [0.46-1.05] or spinal cord compression 0.71 [0.47-1.08]. However, reduction in orthopaedic surgery was significant in studies that lasted over a year 0.59 [0.39-0.88]. Bisphosphonates significantly increased the time to first SRE but did not affect survival. Subanalyses were performed for disease groups, drugs and route of administration. Most evidence supports the use of intravenous aminobisphosphonates. For adjuvant use of bisphosphonates, Clodronate, given to patients with primary operable breast cancer and no metastatic disease, significantly reduced the number of patients developing bone metastases. This benefit was not maintained once regular administration had been discontinued. Two trials reported significant survival advantages in the treated groups. Bisphosphonates reduce the number of bone metastases in patients with both early and advanced breast cancer. Bisphosphonates are well tolerated with a low incidence of side-effects. Economic modelling showed that for acute hypercalcaemia, drugs with the longest cumulative duration of normocalcaemia were most cost-effective. Zoledronate 4 mg was the most costly, but most cost-effective treatment. For skeletal morbidity, Markov models estimated that the overall cost of bisphosphonate therapy to prevent an SRE was GBP250 and GBP1500 per event for patients with breast cancer and multiple myeloma, respectively. Bisphosphonate treatment is sometimes cost-saving in breast cancer patients where fractures are prevented. CONCLUSIONS: High dose aminobisphosphonates are most effective for the treatment of acute hypercalcaemia and delay time to relapse. Bisphosphonates significantly reduce SREs and delay the time to first SRE in patients with bony metastatic disease but do not affect survival. Benefit is demonstrated after administration for at least 6-12 months. The greatest body of evidence supports the use of intravenous aminobisphosphonates. Further evidence is required to support use in the adjuvant setting.

Systematic review of role of bisphosphonates on skeletal morbidity in metastatic cancer.

OBJECTIVE: To review the evidence for the use of bisphosphonates to reduce skeletal morbidity in cancer patients with bone metastases. DATA SOURCES: Electronic databases, scanning reference lists, and consultation with experts and pharmaceutical companies. Foreign language papers were included. STUDY SELECTION: Included trials were randomised controlled trials of patients with malignant disease and bone metastases who were treated with oral or intravenous bisphosphonate compared with another bisphosphonate, placebo, or standard care. All trials measured at least one outcome of skeletal morbidity. RESULTS: 95 articles were identified; 30 studies fulfilled inclusion criteria. In studies that lasted > or = 6 months, compared with placebo bisphosphonates significantly reduced the odds ratio for fractures (vertebral 0.69, 95% confidence interval 0.57 to 0.84, P < 0.0001; non-vertebral 0.65, 0.54 to 0.79, P < 0.0001; combined 0.65, 0.55 to 0.78, P < 0.0001), radiotherapy (0.67, 0.57 to 0.79, P < 0.0001), and hypercalcaemia (0.54, 0.36 to 0.81, P = 0.003) but not for orthopaedic surgery (0.70, 0.46 to 1.05, P = 0.086) or spinal cord compression (0.71, 0.47 to 1.08, P = 0.113). The reduction in orthopaedic surgery was significant in studies that lasted over a year (0.59, 0.39 to 0.88, P = 0.009). Use of bisphosphonates significantly increased time to first skeletal related event but did not increase survival. Subanalyses showed that most evidence supports use of intravenous aminobisphosphonates. CONCLUSIONS: In people with metastatic bone disease bisphosphonates significantly decrease skeletal morbidity, except for spinal cord compression and increased time to first skeletal related event. Treatment should start when bone metastases are diagnosed and continue until it is no longer clinically relevant.

Do hospital palliative care teams improve symptom control? Use of a modified STAS as an evaluation tool.

The support team assessment schedule (STAS) has previously been validated as an evaluation tool for community palliative care teams and inpatient units. This study reports on use of an expanded STAS (E-STAS) to determine symptom prevalence and outcome for inpatients and outpatients referred to a multiprofessional hospital palliative care team. E-STAS forms were completed on patients at referral and twice weekly thereafter. Between August 1996 and May 1997, 352 patients had one or more E-STAS forms completed; 122 of this group had three or more assessments. One-hundred-and-eighty-two patients were male and 170 were female, the median age was 68.5 years (range 26-101 years) and all but 27 (8%) had malignant disease. Of the symptoms assessed on referral, the most common were psychological distress 93%, anorexia 73%, pain 59%, mouth discomfort 59%, depression 40%, constipation 36%, breathlessness 32%, nausea 24% and vomiting 13%. In the 122 patients where three or more assessment were completed, statistically significant improvements from first to last assessment were seen in all symptoms except depression. This study suggests that E-STAS may be a useful tool to evaluate interventions by a hospital palliative care team in patients with advanced disease.

Cuffed polyurethane catheter for ambulatory infusional chemotherapy.

This article describes the technique for inserting cuffed polyurethane catheters under local anaesthesia. A very low complication rate is seen with these catheters and patients tolerate the catheters and Cadd infusional pumps for continuous chemotherapy very well.

Pilot studies of 2 and 1 course carboplatin as adjuvant for stage I seminoma: should it be tested in a randomized trial against radiotherapy?

PURPOSE: Underpinned by increased confidence in cure of metastatic seminoma by chemotherapy during the past 12 years, three management strategies for Stage I seminoma have been evaluated by six collaborating centers within the Anglian Germ Cell Tumor Group. This paper evaluates the efficacy of surveillance, prophylactic radiotherapy and adjuvant chemotherapy, and discusses these differing management approaches. METHODS AND MATERIALS: Patients were recruited into the study between 1982 and 1992. There was no randomization between treatment groups. Seventy-nine patients received prophylactic radiotherapy (median follow-up = 51 months), 67 patients had surveillance alone (median follow-up = 61 months) and 78 patients were treated with adjuvant single agent platinum (median follow-up = 44 months). Fifty-three of these patients received two courses of platinum (median follow-up = 51 months) and 25 patients received one course (median follow-up = 29 months, range 22-72 months). RESULTS: There were 18 (27%) recurrences on surveillance, five (6%) after radiotherapy, one (1%) after two courses of adjuvant single agent platinum and none after one course of carboplatin. There was one death from testis cancer after radiotherapy and none after adjuvant chemotherapy treatments. Two patients died with drug resistant disease after relapse on surveillance. There was one death from a myocardial infarction after prophylactic radiotherapy and one death from suicide in the surveillance group. A retrospective quality of life questionnaire reviewing the incidence of early and late toxicity revealed no major differences though they suggest that those treated with one course adjuvant carboplatin had somewhat less sickness and an earlier return to work. CONCLUSION: Single agent carboplatin appears well tolerated and is an effective adjuvant treatment for Stage I seminoma. A multicenter randomized trial of the different treatment modalities is required to further evaluate its use.

Protracted oral etoposide in epithelial ovarian cancer: a phase II study in patients with relapsed or platinum-resistant disease.

This phase II study evaluates the efficacy and toxicity of a prolonged schedule of oral etoposide in patients with measurable advanced ovarian cancer resistant to, or relapsed following, platinum-based chemotherapy. Forty-seven patients participated, 20 of whom had received more than one prior treatment. Seventy-seven per cent had evidence of disease progression during or within 6 months of the previous chemotherapy. Initially, oral etoposide, 50 mg b.d. (regardless of patient size), was given for 14 days on a 21-day cycle. However, after encountering toxicity, the schedule was modified to 7 days' treatment escalating to 10 then 14 days if well tolerated. Among 41 assessable patients there were two complete and eight partial objective responses (24% response rate; 95% confidence interval 12-41%). Nine further patients (22%) had stable disease, four with a sustained fall of > 50% in CA-125. Median duration of response or stable disease was 35 weeks (range 21-49). Overall median survival was 41 weeks from study entry (range 2 to 96+ weeks). Toxicity for most patients was mild, but sporadic severe myelotoxicity occurred, with two treatment-related deaths. Risk factors for severe toxicity were: performance status 3; hepatic impairment; renal impairment. We conclude that oral etoposide has activity in platinum-resistant ovarian cancer and that it is a useful palliative therapy. It has significant toxicity which may be avoided by appropriate patient selection and an escalating-duration schedule.