Effects of opioids on immunologic parameters that are relevant to anti-tumour immune potential in patients with cancer: a systematic literature review.

BACKGROUND: The immune system has a central role in controlling cancer, and factors that influence protective antitumour immunity could therefore have a significant impact on the course of malignant disease. Opioids are essential for the management of cancer pain, and preclinical studies indicate that opioids have the potential to influence these tumour immune surveillance mechanisms. The aim of this systematic literature review is to evaluate the clinical effects of opioids on the immune system of patients with cancer. METHODS: A systematic search of Ovid MEDLINE (PubMed) and Embase, Cochrane database and Web of Knowledge for clinical studies, which evaluated the effects of opioids on the immune system in patients with cancer, was performed. RESULTS: Five human studies, which have assessed the effects of opioids on the immune system in patients with cancer, were identified. Although all of these evaluated the effect of morphine on immunologic end points in patients with cancer, none measured the clinical effects. CONCLUSIONS: Evidence from preclinical, healthy volunteer and surgical models suggests that different opioids variably influence protective anti-tumour immunity; however, actual data derived from cancer populations are inconclusive and definitive recommendations cannot be made. Appropriately designed and powered studies assessing clinical outcomes of opioid use in people with cancer are therefore required to inform oncologists and others involved in cancer care about the rational use of opioids in this patient group.

Endocrine, metabolic, nutritional and body composition abnormalities are common in advanced intensively-treated (transplanted) multiple myeloma.

Modern treatment strategies have increased life expectancy in multiple myeloma, but little is known about the endocrine, metabolic and nutritional status of long-term survivors. We performed endocrine, metabolic, bone, body composition and nutritional evaluations in 32 patients with intensively-treated, advanced but stable, myeloma a median duration of 6 years from diagnosis and three lines of intensive treatment, including at least one haematopoietic SCT procedure. All patients were off active treatment. There was a high prevalence of endocrine dysfunction: hypothyroidism (9%), hypogonadism (65% males) and elevated prolactin (19%). Adrenocortical function was preserved despite large cumulative corticosteroid pretreatment. Biochemical markers were consistent with postmenopausal status in all females and infertility in males. Nutritionally, 59% were vitamin D insufficient/deficient, reduced serum folate in 25% and vitamin B12 in 6%. Total body DEXA scanning confirmed 'sarcopenic-obesity' in 65%, but reduced bone density was seen in a minority. We conclude that potentially correctable endocrine, metabolic and nutritional abnormalities are prevalent in heavily-treated patients with stable multiple myeloma. Preservation of bone supports the efficacy of bisphosphonate treatment from diagnosis, but sarcopenic-obesity may contribute to frailty. Ultimately, multi-system screening and appropriate interventions may optimise quality of long-term survival and further studies are warranted.

Holistic needs assessment in advanced, intensively treated multiple myeloma patients.

PURPOSE: It is recommended that patients with multiple myeloma should be assessed for unmet holistic needs at key times in their disease trajectory. The aim of this exploratory study was to characterise the holistic needs of advanced, intensively treated multiple myeloma using a structured assessment tool. METHODS: Patients with multiple myeloma who had undergone a haematopoietic stem cell transplantation and subsequent treatment for at least one episode of progressive disease but were in stable plateau phase were included in the study. Patients' holistic needs were assessed using the self-reporting tool, Sheffield Profile for Assessment and Referral for Care (SPARC). RESULTS: Thirty-two patients with a median age of 60 years at assessment and a median of 5.5 years from diagnosis were recruited. Using the SPARC, half of the patients reported tiredness as 'quite a bit/very much,' while one third complained that daytime somnolence and insomnia were 'quite a bit/very much.' Forty-four percent of patients reported pain. One third of patients were bothered and distressed by the side effects from their treatment and were worried about long-term effects of their treatment. Thirty-one percent of patients felt that the effect of their condition had an impact on their sexual life, and 40 % were worried about the effect that their illness was having on their family or other people. CONCLUSION: This is the first study to use a self-reported holistic needs assessment tool in multiple myeloma. A multidimensional structured questionnaire like the SPARC could provide a useful first step in the effective delivery of supportive and palliative care for patients with multiple myeloma.

Why do hospital mastectomy rates vary? Differences in the decision-making experiences of women with breast cancer.

BACKGROUND: Hospital mastectomy rates vary. This study explores the relationship between mastectomy rates and breast cancer patients' consultation and decision-making experiences with specialist clinicians. METHODS: Qualitative semi-structured interviews were conducted with 65 patients from three purposively selected breast units from a single UK region. Patients provided with a choice of breast cancer surgery (breast conservation therapy (BCT) or mastectomy) were purposively recruited from high, medium and low case-mix-adjusted mastectomy rate units. RESULTS: Low mastectomy rate unit patients' consultation and decision-making experiences were markedly different to those of the medium and high mastectomy rate breast units. Treatment variation was associated with patients' perception of the most reassuring and least disruptive treatment; the content and style of information provision (equipoise or directed); level of patient participation in decision making; the time and process of decision making and patient autonomy in decision making. The provision of more comprehensive less directive information and greater autonomy, time and support of independent decision making were associated with a lower uptake of BCT. CONCLUSION: Variation in hospital mastectomy rates was associated with differences in the consultation and decision-making experiences of breast cancer patients. Higher mastectomy rates were associated with the facilitation of more informed autonomous patient decision making.

Palliative care services for those with chronic lung disease.

Excellent palliative care is available for patients with advanced lung cancer. Whether the same services are available for those with nonmalignant respiratory disease is less clear. A questionnaire was sent to 210 named respiratory physicians, each representing a major hospital in England, Wales, and Northern Ireland. A total of 107 replies were received; the response rate was 51.0%. Respondents cared for patients with chronic obstructive pulmonary disease, asbestosis, and diffuse parenchymal lung disease but only a third had responsibility for cystic fibrosis. Physicians were supported by a mean of 3.4 respiratory nurse specialists per department and 73.8% had a specialist lung cancer nurse. In only 16 cases (20.3%) did that nurse extend care to those with nonmalignant disease. Only a minority reported easy access to hospice in-patient care or day care. About 21.5% of the respondents had formal policies in place for care of patients with chronic respiratory disease nearing the end of life, but 87.9% of respondents had no formal process for initiating end of life discussions with those with terminal respiratory illness. Patients with advanced nonmalignant respiratory disease have less universal access to specialist palliative care services than do those with malignant lung disease, and in the majority of hospitals there is no formalized approach to end of life care issues with patients with chronic lung disease.

Efficacy and safety of transdermal fentanyl and sustained-release oral morphine in patients with cancer and chronic non-cancer pain.

PURPOSE: To evaluate effectiveness and safety information of transdermal fentanyl (TDF) (Duragesic/Durogesic) and sustained-release oral morphine (SRM) in cancer pain (CP) and chronic non-cancer pain (NCP), a pooled analysis was conducted on datasets of published, open label, uncontrolled (no comparator group) and randomised controlled (with SRM as comparator) studies of TDF. PATIENTS AND METHODS: Eight trials with treatment durations of at least 28 days met the inclusion criteria. The effectiveness analysis assessed changes in average pain and pain 'right now' scores between baseline and Day 28. The safety analysis evaluated the incidence of adverse events (AEs) reported within the first 28 days of treatment with TDF or SRM. Subgroup analyses included pain type, gender, age, weight, and body mass index. RESULTS: Pooled efficacy data were available from 1220 patients; these showed that both TDF and SRM were effective in improving pain 'right now' scores (0-100 scale) from baseline to Day 28. The improvement was significantly more pronounced in the TDF treatment group (-26.7 +/- 31.3 for TDF, -18.7 +/- 30.9 for SRM, p = 0.002). This favourable effect of TDF was most apparent amongst patients with NCP. Data concerning AEs were available from over 2500 patients with CP (3 out of 10 patients) or chronic NCP (7 out of 10 patients). Significantly fewer patients in the TDF than in the SRM group reported any AE (72% vs. 87% respectively; p < 0.001), or an AE leading to the study drug being permanently discontinued (16% vs. 23% respectively; p < 0.001). Constipation and somnolence occurred considerably less frequently in the TDF than in the SRM treatment group. This difference was statistically significant in both the CP and NCP subgroups. CONCLUSION: This pooled data analysis provides expanded insight into the safety and effectiveness profile of transdermal fentanyl in patients with chronic pain. It shows significantly improved pain relief with transdermal fentanyl compared with sustained-release oral morphine, and supports current evidence of favourable tolerability of transdermal fentanyl, particularly with regard to reduced constipation and somnolence.

A new international framework for palliative care.

In spite of recent advances in anti-cancer treatments, most adult cancer patients still ultimately die from their disease. There should therefore be free access to palliative care around the clock and seven days a week, for all cancer patients, as a fundamental human right. At present, the implementation of palliative care and patients' access to it are inconsistent across Europe and many other parts of the world. The World Health Organisation (WHO) made an important advance in 1986 by first defining palliative care and, then updating this definition in 2002. However, this definition could benefit from further refinement in order to reflect the increasing multi-professional specialisation in this subject, and to recognise the different models for delivering this type of care. We recommend that palliative care should be defined as follows: Palliative care is the person-centred attention to symptoms, psychological, social and existential distress in patients with limited prognosis, in order to optimise the quality of life of patients and their families or close friends. Based on this definition, we propose two further types of palliative care which reflect the reality of how palliative care is actually delivered: Basic palliative care is the standard of palliative care which should be provided by all healthcare professionals, in primary or secondary care, within their normal duties to patients with life-limiting disease. Specialised palliative care is a higher standard of palliative care provided at the expert level, by a trained multi-professional team, who must continually update their skills and knowledge, in order to manage persisting and more complex problems and to provide specialised educational and practical resources to other non-specialised members of the primary or secondary care teams. If a patient has difficult symptoms which cannot be controlled by his/her current healthcare team, he/she has a right to be referred, and the current healthcare provider has an obligation to refer, to the local palliative care team. Important priorities to ensure the standardisation of, and uniform access to, palliative care for all cancer patients include: Integration of palliative care services with the primary care and oncology teams. Establishment of a specialised palliative care service in each major cancer centre. Establishment of educational programmes covering palliative care for undergraduates, oncologists, primary care team members and specialists training in palliative care. Support for research using appropriate methodologies to underpin the scientific basis of palliative care. Establishment of quality assurance programmes. Recognition of palliative medicine as a medical specialty. Establishment of academic centres of excellence with chairs of palliative medicine and palliative care nursing. Removal of unnecessary restrictions on all drugs which are proven to be of benefit in symptom control, especially improving access to strong opioids. Improved information for patients and family carers to allow them to make choices and exercise autonomy.

Systematic review of the problems and issues of accessing specialist palliative care by patients, carers and health and social care professionals.

OBJECTIVES: To determine the problems and issues of accessing specialist palliative care by patients, informal carers and health and social care professionals involved in their care in primary and secondary care settings. DATA SOURCES: Eleven electronic databases (medical, health-related and social science) were searched from the beginning of 1997 to October 2003. Palliative Medicine (January 1997-October 2003) was also hand-searched. STUDY SELECTION: Systematic search for studies, reports and policy papers written in English. DATA EXTRACTION: Included papers were data-extracted and the quality of each included study was assessed using 10 questions on a 40-point scale. RESULTS: The search resulted in 9921 hits. Two hundred and seven papers were directly concerned with symptoms or issues of access, referral or barriers and obstacles to receiving palliative care. Only 40 (19%) papers met the inclusion criteria. Several barriers to access and referral to palliative care were identified including lack of knowledge and education amongst health and social care professionals, and a lack of standardized referral criteria. Some groups of people failed to receive timely referrals e.g., those from minority ethnic communities, older people and patients with nonmalignant conditions as well as people that are socially excluded e.g., homeless people. CONCLUSIONS: There is a need to improve education and knowledge about specialist palliative care and hospice care amongst health and social care professionals, patients and carers. Standardized referral criteria need to be developed. Further work is also needed to assess the needs of those not currently accessing palliative care services.

A new quality assurance package for hospital palliative care teams: the Trent Hospice Audit Group model.

Cancer patients in hospitals are increasingly cared for jointly by palliative care teams, as well as oncologists and surgeons. There has been a considerable growth in the number and range of hospital palliative care teams (HPCTs) in the United Kingdom. HPCTs can include specialist doctors and nurses, social workers, chaplains, allied health professionals and pharmacists. Some teams work closely with existing cancer multidisciplinary teams (MDTs) while others are less well integrated. Quality assurance and clinical governance requirements have an impact on the monitoring of such teams, but so far there is no standardised way of measuring the amount and quality of HPCTs' workload. Trent Hospice Audit Group (THAG) is a multiprofessional research group, which has been developing standards and audit tools for palliative care since the 1990s. These follow a format of structure-process-outcome for standards and measures. We describe a collaborative programme of work with HPCTs that has led to a new set of standards and audit tools. Nine HPCTs participated in three rounds of consultation, piloting and modification of standard statements and tools. The final pack of HPCT quality assurance tools covers: policies and documentation; medical notes review; questionnaires for ward-based staff. The tools measure the HPCT workload and casemix; the views of ward-based staff on the supportive role of the HPCT and the effectiveness of HPCT education programmes, particularly in changing practice. The THAG HPCT quality assurance pack is now available for use in cancer peer review.

A double-blind, randomised, controlled Phase II trial of Heliox28 gas mixture in lung cancer patients with dyspnoea on exertion.

Helium has a low density and the potential of reducing the work of breathing and improving alveolar ventilation when replacing nitrogen in air. A Phase II, double-blind, randomised, prospective, controlled trial was undertaken to assess whether Heliox28 (72% He/28% O(2)) compared with oxygen-enriched air (72% N(2)/28% O(2)) or medical air (78.9% N(2)/21.1% O(2)) could reduce dyspnoea and improve the exercise capability of patients with primary lung cancer and dyspnoea on exertion (Borg >3). A total of 12 patients (seven male, five female patients, age 53-78) breathed the test gases in randomised order via a facemask and inspiratory demand valve at rest and while performing 6-min walk tests. Pulse oximetry (SaO(2)) was recorded continuously. Respiratory rate and dyspnoea ratings (Borg and VAS) were taken before and immediately post-walk. Breathing Heliox28 at rest significantly increased SaO(2) compared to oxygen-enriched air (96+/-2 cf. 94+/-2, P<0.01). When compared to medical air, breathing Heliox28 but not oxygen-enriched air gave a significant improvement in the exercise capability (P<0.0001), SaO(2) (P<0.05) and dyspnoea scores (VAS, P<0.05) of lung cancer patients.

Long-term observations of patients receiving transdermal fentanyl after a randomized trial.

We observed 73 cancer patients receiving transdermal fentanyl for 1-29 (mean 5.5) months immediately after participation in a randomized clinical trial. Of these, 32 received fentanyl until death, 18 were lost to follow-up, 11 required alternative analgesia, and 12 withdrew for other reasons. The median first recorded dose (not necessarily the patient's first fentanyl dose) was 75 microg/h. The median final dose was 100 microg/h. All but 3 patients required <300 microg fentanyl/h. In the 16 who received fentanyl for > or =3 months until death, the median dose was unchanged (100 microg/h) 3 months before death and at death; 8/16 required no dosage change. The incidence of constipation, skin reactions, nausea, and vomiting was low. No significant respiratory depression was associated with fentanyl. Most patients (85%) and investigators (86%) rated the treatment as good or excellent. We conclude that long-term treatment with transdermal fentanyl is safe and acceptable to many cancer patients.

How many inpatients at an acute hospital have palliative care needs? Comparing the perspectives of medical and nursing staff.

The primary aim of this prospective face-to-face interview survey was to identify the proportion of inpatients at an acute hospital (Royal Hallamshire Hospital, Sheffield, UK) considered to have palliative care needs by medical and nursing staff directly responsible for their care. During the 1-week period of the survey (6-10 September 1999), 452 inpatients were present in the hospital. Nursing staff were interviewed for 99% of patients; medical staff for 81%. Staff interview data were supplemented by case note review. Overall, 23% of the total inpatient population were identified as having palliative care needs and/or being terminally ill by staff and 11% were considered suitable for referral to a specialist palliative care bed. However, there was a low level of concurrence between medical and nursing staff as to which individual patients had palliative care needs (although this increased with perceived increased proximity to death), including which would be suitable for referral to a specialist palliative care bed. A need for further palliative care education for medical and nursing staff working within acute hospital settings was identified to ensure that the best use is made of hospital-based specialist palliative care services.

The management of neuropathic pain in cancer: clinical guidelines for the use of adjuvant analgesics.

Neuropathic pain is seen in a third of cancer patients and is not always responsive to traditional analgesics. We describe practical guidelines for the use antidepressants and anticonvulsants as adjuvant analgesics in such situations. Newer adjuvant analgesics, interventional procedures and options for the management of pain emergencies, are also briefly outlined.

Using bisphosphonates to control the pain of bone metastases: evidence-based guidelines for palliative care.

This work was undertaken by the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland (APM) as a demonstration project in developing clinical guidelines relevant to palliative care from a pragmatic approach to literature review and grading of clinical evidence. CANCERLIT and Embase were searched for relevant papers written in English, published since 1980. Each study identified was rated against agreed criteria for levels of evidence. Most studies were not specifically designed to define speed of response, and were not undertaken in palliative care patients. Thus, careful reading and grading of each study was necessary. Sufficient evidence was identified to make recommendations for clinical practice in a palliative care population of patients, and areas for future research have been identified. Bisphosphonates appear to have a role in managing pain from metastases which has been refractory to conventional analgesic management and where oncological or orthopaedic intervention is delayed or inappropriate.