Comparative pilot study of symptoms and quality of life in cancer patients and patients with end stage renal disease.

BACKGROUND: Patients with advanced renal failure are increasingly opting for conservative treatment, yet little is known of their palliative care needs. METHODS: We performed a cross-sectional study, examining symptom burden and quality of life in patients with advanced renal failure (estimated GFR < 17 mL/min; n = 11). A contemporary cohort with terminal malignancy acted as comparators (n = 11). Symptom burden was scored using an extended Memorial Symptom Assessment Scale Short Form questionnaire. Quality of life was assessed using the Euroqol-5Q questionnaire. Demographic and pathological data, performance status and co-morbidity were also recorded. RESULTS: Baseline characteristics were similar for the two groups. Symptom burden (renal 17; cancer 15; P =NS) and quality of life scores (renal 60; cancer 60; P =NS) were remarkably similar. Both groups reported high levels of psychological distress. CONCLUSIONS: Patients with advanced renal failure experience a symptom burden and impairment of quality of life similar to that of patients with terminal malignancy.

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.

A prospective, within-patient comparison between metal butterfly needles and Teflon cannulae in subcutaneous infusion of drugs to terminally ill hospice patients.

We performed a prospective study of hospice in-patients requiring a syringe driver (SD), to determine the site duration and tolerability of metal butterfly needles compared to Teflon cannulae. Using patients as their own control, prescribed medications were divided equally between two SDs (Graseby MS16a), for delivery over 24 h. A butterfly infusion (Flosafer, 25 gauge) was connected to one SD and a Teflon cannula (Abbocath-T, 24 gauge), to the second. These were inserted subcutaneously (s.c.) on opposite sides of the body at comparable sites; oedematous, broken or painful sites were excluded. SD sites were examined at 4-hourly intervals. The study was terminated when both devices had required resiting. Needle and cannula times were compared using the Wilcoxon signed rank test. Thirty patients entered the study, 13 males and 17 females, mean age (standard deviation): 70 (11) years. Thirteen patients completed the study. Nine patients died and eight patients discontinued the study before both needle and cannula had been resited. All 30 patients are included in the analysis. The time from insertion to resiting of the cannula was significantly longer than the needle: P < 0.0002, median (range) 93.5 (22.8-263.5) h versus 42.8 (7.5-162.3) h, respectively. The cost of the needle versus cannula is 1.93 Pounds versus 2.51 Pounds, respectively. Teflon cannulae have a median life span twice that of metal butterfly needles and are a cost-effective alternative for administration of medications by s.c. infusion in terminally ill patients.

Recurrent locally advanced breast cancer: the treatment of chest wall disease with further chemotherapy.

Locally recurrent advanced breast cancer is associated with significant morbidity and one aim of treatment is to control chest wall disease. There are no published data on the efficacy of subsequent courses of chemotherapy in this setting. We reviewed the case notes of 22 patients who developed locally recurrent breast cancer despite having received previous surgery, radiotherapy and one prior course of chemotherapy for local disease. These patients were treated with further systemic chemotherapy in an attempt to palliate their symptoms and control recurrent disease. The overall objective response rate observed with chemotherapy was 26% and a further 45% had stabilization of disease during treatment. Time to progression of disease was longest with anthracycline-based regimens; this decreased with subsequent lines of treatment. Chemotherapy was a safe and effective treatment modality in the care of women with locally recurrent breast cancer. A prospective database will now be established to collect further information on this group of patients, including their quality of life.