Abstract: Breathlessness (or dyspnoea) is a common symptom experienced by cancer patients. It may be iatrogenic and is often caused or aggravated by co-morbidity. Recent studies have elucidated the neural and chemical controls of breathing which may be involved in the production of dyspnoea. A rational approach involves making a diagnosis of aetiology and treating reversible causes wherever possible. The main approaches for palliation of dyspnoea include anti-cancer treatments; drugs; oxygen and airflow; non-medical approaches. Further research is needed to clarify the best pharmacological regimens and the place of more invasive interventions.
Abstract: PURPOSE: Eicosapentaenoic acid (EPA) has been proposed to have specific anticachectic effects. This trial compared EPA diethyl ester with placebo in cachectic cancer patients for effects on weight and lean body mass. PATIENTS AND METHODS: Five hundred eighteen weight-losing patients with advanced gastrointestinal or lung cancer were studied in a multicenter, double-blind, placebo controlled trial. Patients were randomly assigned to receive a novel preparation of pure EPA at a dose of 2 g or 4 g daily or placebo (2g EPA, n = 175; 4 g EPA, n = 172; placebo, n = 171). Patients were assessed at 4 weeks and 8 weeks. RESULTS: The groups were well balanced at baseline. Mean weight loss at baseline was 18% (n = 518). Over the 8-week treatment period, both intention-to-treat analysis and per protocol analysis revealed no statistically significant improvements in survival, weight, or other nutritional variables. There was, however, a trend in favor of EPA with analysis of the primary end point, weight, at 8 weeks showing a borderline, nonsignificant treatment effect (P = .066). Relative to placebo, mean weight increased by 1.2 kg with 2 g EPA (95% CI, 0 kg to 2.3 kg) and by 0.3 kg with 4 g EPA (-0.9 kg to 1.5 kg). CONCLUSION: The results indicate no statistically significant benefit from single agent EPA in the treatment of cancer cachexia. Future studies should concentrate on other agents or combination regimens.
Abstract: 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.
Abstract: Advance statements about medical care have been heralded by some as a solution to the problem of end of life decision making for people not able to participate in discussions about their care. Since death is now most likely to occur at the end of a long life, it is important to understand the views and values which older people express in relation to these. This paper reports on a study which used focus groups to explore older people's views about advance statements and the role these might play in end of life care decisions. Participants were 32 older people or their representatives who belonged to six diverse community groups in Sheffield, UK. Advance statements were understood primarily in terms of their potential to aid personal integrity and to help the families of older people by reducing the perceived 'burden' of their decision making. However, concerns were expressed about the perceived link between advance care statements and euthanasia, their future applicability, and the possibility that preferences for care may change. Participants also reported worries and difficulties related to thinking about and discussing death and dying. Trust between doctor and patient, built up over time, was perceived to be important in creating an environment in which the communication necessary to underpin advance care planning could take place. Lastly, participants did not perceive that during dying they would be ready necessarily to adhere to an advance statement and 'disengage' from their lives. We conclude that, rather than emphasising the completion of advance statements, it may be preferable to conceptualise advance care planning as a process of discussion and review between clinicians, patients and families.
Abstract: 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.
Abstract: The aim of this study was to explore the reasons why patients and families are referred to specialist palliative care. Semi-structured interviews were undertaken with patients and professionals from primary care and specialist palliative care services in the north of England. A content analysis of the transcripts was undertaken, key issues were identified and common themes grouped. Twelve professionals working in specialist palliative care, three GPs, six community nurses and thirteen patients were interviewed (n = 34). Five key themes are reported: reasons why patients are referred to specialist palliative care; reasons why patients are not referred to specialist palliative care; timeliness of referrals; continuity of care; and use of referral criteria. It was found that the professionals in primary care would like more training and education about how to refer patients to specialist palliative care and how to deal with issues of death and dying. The patients were generally satisfied with the service but wanted to be able to be supported at home in their final days. Further training and education may improve the knowledge of professionals who refer patients to specialist palliative care. There are currently no standardized criteria in the UK to determine when a referral should be triggered. The development of a set of standardized referral criteria may be useful in aiding a referral decision.
Abstract: This paper presents an exploration of the reasons why breast cancer patients decline entry into randomised clinical trials of adjuvant cancer therapy. The study employed a qualitative, longitudinal design based on in-depth interview post diagnosis, with follow-up interviews at 6 and 12 months later. Twenty-two consecutive patients, newly diagnosed with breast cancer, who had declined entry into a clinical trial were prospectively recruited from five outpatient breast cancer clinics in the North Trent Cancer Network. Analysis of patients' narratives indicated that fear of the illness and limited understanding of medical research in general, compounded by unhelpful explanations of the trial purpose and process by health professionals, resulted in patients opting for the 'tried and tested' treatment. Some patients had persisting guilt about their decision not to take part. Many of the reasons why breast cancer patients decline entry to clinical trials could be addressed, as they tend to be a product of situational and process factors, rather than being rooted in deep-seated antipathy towards research.
Abstract: Pulse oximetry is a valuable, non-invasive method used for estimating oxyhaemoglobin saturation. It can give a bedside indication of the oxygenation and thus provide a valuable insight into the cause of breathlessness. Its use can help palliative care teams to determine the need to prescribe or to withhold oxygen therapy. The technology is well established and relatively inexpensive. Factors that influence readings include low perfusion states at the end of life. With a thorough understanding of its uses and limitations, pulse oximetry can assist multidisciplinary teams in providing better care to ill patients in the palliative care setting.
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: INTRODUCTION: Within the last decade, there have been many government initiatives to promote consumer involvement in research, especially in cancer. At the same time, the number and influence of consumer groups themselves have expanded. However, the organizational infrastructure necessary to facilitate consumer involvement has not been developed. Consequently, consumer involvement has tended to remain essentially localized and project driven, with no strategic or regional lead. OPPORTUNITIES FOR INVOLVEMENT AND IDENTIFICATION OF CONSUMERS: The opportunities for consumers to influence the research process at each stage of the research process are identified. The different types of consumer involvement are also examined. Novel ways of identifying and recruiting consumers that have been adopted by one cancer network are discussed. THE STRATEGIES USED IN ONE CANCER NETWORK: An organizational model designed by one cancer network for involving consumers in research is illustrated. Three innovations are examined in detail. First, how three open consumer conferences have increased awareness of research among service users. Second, the recruitment of consumers to sit on project steering groups and a committee that provides a strategic overview of current research. Third, the establishment of a Consumer Panel for Research where reimbursed, trained consumers are able to provide a considered consumer perspective in a range of settings. CONCLUSIONS: Cancer networks need to take the lead in the development of an organizational infrastructure to facilitate consumer involvement. The model developed in Sheffield could be generalizable to other diseases and other health-care settings.
Abstract: Spiritual care is an important aspect of holistic care. However, it is seldom the subject of audit, or included in quality standards. This article reports on the work of the Trent Hospice Audit Group (THAG) into the development of a quality standard for the assessment, delivery and evaluation of spiritual care. The standard was drafted by a multidisciplinary team and circulated among the THAG user group and other interested specialists, and subsequently revised. Three levels of assessment are defined and the different levels of expertise needed for these assessments identified. Education has been highlighted as a key issue in enabling effective use of the standard package. Although acknowledging possible limitations and the importance of professional judgement, the standard should help provide a consistent approach to assessment, care planning and outcome review of spiritual care.
Abstract: PURPOSE: Non-small-cell lung cancer (NSCLC), a leading cause of cancer-related deaths in both developed and developing countries, heavily impacts patient health-related quality of life (HRQOL). Although recent research has found many positive and significant steps in randomized controlled trials (RCTs) in which HRQOL has been used as an outcome, questions remain regarding methodologic quality and impact value of HRQOL outcome assessments in some RCTs. To date, no detailed systematic review exists of HRQOL methodology in NSCLC RCTs. METHODS: A systematic review using Cochrane methodology evaluated HRQOL components in RCTs. Identified studies were evaluated independently by three reviewers on a broad set of predetermined criteria. RESULTS: Twenty-nine published RCTs (NSCLC patient samples total, N = 8445) with an HRQOL component were identified. Although most trials exhibited good-quality research and useful HRQOL and clinical data, the weaknesses identified in some trials include such common limitations as no clear hypothesis, lack of a clear approach to missing data and data analysis, and limited presentation of results. CONCLUSION: Although it is clear that HRQOL is an important end point in NSCLC RCTs because the information helps to influence treatment recommendations, the identified weaknesses in conducting HRQOL measurement in NSCLC RCTs and the reporting of results need to be addressed.
Abstract: Between October 2001 and May 2002 the Chairperson and Vice-Chairperson of each Multicentre Research Ethics Committee (MREC) in England, Wales and Scotland took part in a semi-structured interview to ascertain the attitudes of MRECs to palliative care research. Interviews were transcribed and analysed using a grounded theory approach. Most respondents said each protocol was reviewed on its own merits, according to broad ethical principles, but were equivocal as to whether palliative care protocols posed particular or different challenges compared to those from other specialties. Respondents said they reviewed only a small number of palliative care protocols, and that they were less experienced with some of the study methods utilized, particularly qualitative designs. Four main themes emerged from the analysis. Respondents expressed concerns about the protocol itself--in regard to safeguarding the principles of autonomy and justice. There were concerns about how the research would be carried out, especially the protection of patients and the influence and input of the researcher in the process. The third theme concerned the impact of the research on the participant, particularly intrusion, potential distress and the existence of support mechanisms. Fourthly, respondents identified patient groups receiving palliative care (children, the elderly, bereaved families, patients in intensive therapy units, and those from ethnic groupings), who they considered might be particularly vulnerable.
Abstract: A comparison of the views of geriatric medicine physicians and intensive care physicians in the United Kingdom on the topics of active voluntary euthanasia and physician-assisted suicide revealed rather different attitudes. Eighty percent of geriatricians, but only 52% of intensive care physicians, considered active voluntary euthanasia as never justified ethically. Gender and age did not play a major part in attitudinal differences of the respondents. If the variability of attitudes of these two medical specialties are anywhere near illustrative of other physicians in the United Kingdom, it would be difficult to formulate and implement laws and policies concerning euthanasia and assisted suicide. In addition, ample safeguards would be required to receive support from physicians regarding legalization.
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: During the last few years several factors have contributed to an increasing change in the medical treatment of advanced colorectal cancer. Among them are the more general acceptance of the impact of chemotherapy on quality of life and survival in first as well as in second-line treatment, the introduction of new drugs and the definition of novel endpoints which can roughly be defined as "patient benefit". For this reason the European Organization for Research and Treatment of Cancer (EORTC) Gastrointestinal Tract Cancer Cooperative Group (GITCCG) felt it was appropriate to organize a workshop with experts from different countries and national groups to discuss in depth several aspects concerning the treatment of patients with advanced colorectal cancer.
Abstract: Cancer patients requiring strong opioid analgesia (n = 202; mean age, 61.5 years; range, 18-89 years; 55% men) were recruited from 38 United Kingdom palliative care centers into a randomized, open, two-period, crossover study comparing transdermal fentanyl with sustained-release oral morphine. Patients received one treatment for 15 days followed immediately by the other for 15 days. Daily diaries were completed. Both treatments appeared equally effective in terms of pain control, as assessed by the Memorial Pain Assessment Card and European Organization for Research and Treatment of Cancer (EORTC) pain scores. Fentanyl was associated with significantly less constipation (p < 0.001) and less daytime drowsiness (p = 0.015) but greater sleep disturbance (p = 0.004) and shorter sleep duration (p = 0.008) than morphine. The World Health Organization (WHO) performance status and EORTC global quality of life scores showed no significant difference between treatment groups. Of those patients who were able to express a preference (n = 136), significantly more preferred the fentanyl patches (p = 0.037). We conclude that, in this study, transdermal fentanyl provided pain relief that was acceptable to cancer patients and was associated with less constipation and sedation than morphine. These reduced side effects may contribute to patients preference for the patches.
Abstract: Pain is the most feared symptom for patients diagnosed with cancer. Although our understanding of cancer pain and its management has greatly improved in the past decade, an unacceptably large proportion of patients still do not receive adequate pain relief. Before commencing any form of treatment, patients must receive a thorough assessment in order to define the pain, causes and severity. The recommendations for progressing a patient from step 2 to step 3 of the WHO analgesic ladder are discussed here as well as the choice of strong opioid substitution. An overview of the benefits of considering alternative routes of administering strong opioids, such as the transdermal delivery of fentanyl (TTS fentanyl), and the use of opioid substitution in patients intolerant to the adverse effects of morphine are also included. Finally, newer approaches to relieving refractory pain, such as neuropathic and bone pain, are considered.
Abstract: Pain affects most patients with malignant disease, and the prevalence of severe pain increases in the advanced stages of the condition. One in 5 patients with cancer has uncontrolled pain, even after 10 years of the use of the World Health Organization programme for cancer pain control and its 'three-step ladder' for the rational use of analgesics including morphine. Morphine has long been the 'gold standard' for the treatment of severe cancer pain. However, its side-effects, particularly sedation, cognitive impairment and myoclonus at high doses, have provoked the use of 'opioid rotation' to alternatives such as methadone and hydromorphone. The new 72-h transdermal patch for fentanyl also offers advantages of reduced side-effects and increased convenience over oral morphine. Intravenous strontium-89 and bisphosphonate therapy are effective for both short- and long-term control of metastatic bone pain. The spinal N-methyl-D-aspartate (NMDA) receptor is important in modulating the plasticity of the central nervous system and in aggravating chronic pain through the phenomenon of 'wind-up'. The NMDA antagonist ketamine, an anaesthetic, can be used at low doses for the management of refractory and neuropathic pains. Among adjuvant drugs, ketorolac has emerged as a potent non-steroidal anti-inflammatory drug. Palliative care is gaining acceptance as a new discipline in healthcare. Its strategic role is being reviewed as an adjunct to cancer therapy at all stages and its use is no longer confined to the terminal phase of disease after curative treatment has failed. Pain control and other aspects of symptom control are, therefore, viewed as an integral part of cancer management.
Abstract: Xerostomia, or dry mouth, is a very common symptom amongst the terminally ill and can have profound negative effects on patients' quality of life. Yet, it is often considered trivial and therefore tends to be neglected and ignored. This review examines the pathophysiology, aetiology and methods of assessing xerostomia and its effects and discusses its management, with particular emphasis upon palliation. If xerostomia is managed sensitively and effectively, it is possible to improve patients' comfort and sense of well-being and so improve overall care.
Abstract: The understanding and treatment of pain is one of the oldest challenges for physicians, scientists and philosophers. Much of our present rationale of pain control is based on the Cartesian idea that pain mostly originates from external or internal noxious stimuli, which are transmitted to and interpreted in the brain. Consequently, removal (blocking) of the stimuli and modification of cerebral awareness have been the prime targets of analgesic interventions. Only recently has the relationship between pain and other physical, psychological and social aspects of illness been considered in the overall management plan. Most of the literature on pain control reveals the physical bias of measurement. Apart from simple but reliable tools such as visual analogue scales and Likert-type verbal scales, more sophisticated measures such as multidimensional pain inventories have also been used when it is necessary to characterise pain more specifically. In clinical studies, it is usual to ask the patient to report on his own pain, although proxy measures such as mobility, performance status and analgesic consumption are also often used. The hospice concept of "total pain", in which the psychological, social, spiritual and other aspects are emphasised, has been influential in our new approach to pain measurement. Particularly when it is chronic and related to advancing disease as in metastatic cancer, pain can interact significantly with many facets of daily living. A holistic model of quality of life in such patients should, therefore, include a multidimensional or modular assessment of these areas. Medical interventions themselves can affect quality of life in both positive and negative ways. Some side-effects may be so common as to be accepted as "normal", e.g. constipation or sedation with opioids: it is only by their careful evaluation, when comparing opioids with essentially similar analgesic potentials, that differential toxicities may be revealed. Simple recording of physical side-effects of drugs is really not sufficient, because analgesics as well as other therapies may be associated with mood changes and broader consequences for quality of life. Only in the past few years has quality of life been seriously addressed in palliation research. For example, standardised quality of life scales are now included almost routinely in oncological studies involving radiotherapy or chemotherapy by the Medical Research Council (MRC) of Great Britain. Trials of the new biphosphonates, which can reduce bone pain in metastatic cancer, have been enhanced by incorporating quality of life measures. Based on the experience from earlier efficacy/safety studies with the new transdermal route of drug delivery for the opioid fentanyl, important areas of life such as sleep and cognitive function have been addressed. Randomised controlled trials of analgesics which include quality of life endpoints are still rare, but should be encouraged as these represent the most rigorous way of evaluating new therapies. The current preoccupation with quality assurance in healthcare is directed, ultimately, to the delivery of a better quality of care, which should also be more cost-effective, for large populations. An important intermediate step towards that ideal is the collection of data on pain and other symptoms, but also validated quality of life parameters on well-defined groups. Only by widening the scope of analgesic studies to include these dimensions can we hope to define appropriate strategies for more rational healthcare.
Abstract: Although intracranial metastases from malignant pleural mesothelioma are rare, their presence should be suspected in cases of high-grade mesothelioma and should possibly be included in routine preoperative evaluation. An unusual case of cerebral metastases from pleural mesothelioma is presented and the literature is reviewed.
Abstract: A study was conducted to determine the patterns of opioid use in patients under the care of specialist palliative care (SPC) teams in Trent Region, both in the community and in inpatient settings. The design was a survey of point prevalence by case note and drug chart review. The case notes and prescription records of 1007 patients were reviewed, and data collected on age, sex, diagnosis, date of referral, care settings, opioid form and dose on referral, and most recent opioid form and dose. Nine hundred and seventy patients had cancer; their ages ranged from 18 to 98 years (mean 66.5; median 69). Care was delivered by community specialist nurse for 39%, hospice daycare (DC) for 31%, hospice based homecare for 11%, hospice inpatient unit (IPU) for 15%, hospice outpatient (OP) for 5%, and other for 0.5%. There was no record of medication in 2% of the notes. No opioids had been prescribed for 43% of patients (range 24% IPU to 49% DC), 10% of patients were using weak opioids only (range 0.9% IPU to 16% OP), and 45% of patients were using strong opioids (range 39% DC to 75% IPU), the majority being on morphine (87% of total strong opioids). Daily oral morphine equivalence (OME) dosages ranged form 0.4 mg to 3600 mg (mean 166; median 60; mode 60). Dose changes under SPC ranged from -780 mg to +3900 mg OME, 42% patients having had no change in their dosage and 15% having reduced their opioid dose whilst under SPC. This survey challenges the popular impression that patients receiving SPC require large doses of morphine. The highest prevalence of potent opioid prescribing was in hospice IPUs, largely owing to the use of parenteral diamorphine. Conversely, IPUs had the lowest prevalence of weak opioids. Staff caring for patients with cancer must consider the need for downward as well as upward titration of opioid dosages.
Abstract: The synthetic opioid dipipanone is infrequently used in the UK in the management of malignant pain, principally because of the inflexibility of the Diconal combination preparation (dipipanone 10 mg with cyclizine 30 mg). We present three patients in which dipipanone elixir proved to be their own drug of choice in the management of opioid responsive cancer pain, and our experience with 15 other patients. Dipipanone elixir was formulated 10 mg/5 ml, in single strength chloroform water.
Abstract: The EORTC Study Group on Quality of Life has developed a modular system for assessing the quality of life of cancer patients in clinical trials composed of two basic elements: (1) a core quality of life questionnaire, the EORTC QLQ-C30, covering general aspects of health-related quality of life, and (2) additional disease- or treatment-specific questionnaire modules. Two international field studies were carried out to evaluate the practicality, reliability and validity of the core questionnaire, supplemented by a 13-item lung cancer-specific questionnaire module, the EORTC QLQ-LC13. In this paper, the results of an evaluation of the QLQ-LC13 are reported. The lung cancer questionnaire module comprises both multi-item and single-item measures of lung cancer-associated symptoms (i.e. coughing, haemoptysis, dyspnoea and pain) and side-effects from conventional chemo- and radiotherapy (i.e. hair loss, neuropathy, sore mouth and dysphagia). It was administered to patients with non-resectable lung cancer recruited from 17 countries. In total, 883 and 735 patients, respectively, completed the questionnaire prior to and once during treatment. The symptom measures discriminated clearly between patients differing in performance status. All item scores changed significantly in the expected direction (i.e. lung cancer symptoms decreased and treatment toxicities increased) during treatment. With one exception (problems with a sore mouth), the change of toxicity measures over time was related specifically to either chemo- or radiotherapy. However, the single item on neuropathy did not measure adequately the full range of symptoms. The hypothesised scale structure of the questionnaire was partially supported by the data. The multi-item dyspnoea scale met the minimal standards for reliability (Cronbach alpha coefficient > 0.70), while the pain items did not form a scale with reliability estimates acceptable for group comparisons. In conclusion, the results form international field testing lend support to the EORTC QLQ-LC13 as a clinically valid and useful tool for assessing disease- and treatment-specific symptoms in lung cancer patients participating in clinical trials, when combined with the EORTC core quality of life questionnaire. In a few areas, however, the questionnaire module could benefit from further refinements. In addition, its performance over a longer period of time still needs to be investigated.
Abstract: BACKGROUND: In 1986, the European Organization for Research and Treatment of Cancer (EORTC) initiated a research program to develop an integrated, modular approach for evaluating the quality of life of patients participating in international clinical trials. PURPOSE: We report here the results of an international field study of the practicality, reliability, and validity of the EORTC QLQ-C30, the current core questionnaire. The QLQ-C30 incorporates nine multi-item scales: five functional scales (physical, role, cognitive, emotional, and social); three symptom scales (fatigue, pain, and nausea and vomiting); and a global health and quality-of-life scale. Several single-item symptom measures are also included. METHODS: The questionnaire was administered before treatment and once during treatment to 305 patients with nonresectable lung cancer from centers in 13 countries. Clinical variables assessed included disease stage, weight loss, performance status, and treatment toxicity. RESULTS: The average time required to complete the questionnaire was approximately 11 minutes, and most patients required no assistance. The data supported the hypothesized scale structure of the questionnaire with the exception of role functioning (work and household activities), which was also the only multi-item scale that failed to meet the minimal standards for reliability (Cronbach's alpha coefficient > or = .70) either before or during treatment. Validity was shown by three findings. First, while all interscale correlations were statistically significant, the correlation was moderate, indicating that the scales were assessing distinct components of the quality-of-life construct. Second, most of the functional and symptom measures discriminated clearly between patients differing in clinical status as defined by the Eastern Cooperative Oncology Group performance status scale, weight loss, and treatment toxicity. Third, there were statistically significant changes, in the expected direction, in physical and role functioning, global quality of life, fatigue, and nausea and vomiting, for patients whose performance status had improved or worsened during treatment. The reliability and validity of the questionnaire were highly consistent across the three language-cultural groups studied: patients from English-speaking countries, Northern Europe, and Southern Europe. CONCLUSIONS: These results support the EORTC QLQ-C30 as a reliable and valid measure of the quality of life of cancer patients in multicultural clinical research settings. Work is ongoing to examine the performance of the questionnaire among more heterogenous patient samples and in phase II and phase III clinical trials.
Abstract: Palliative (terminal) care is now recognized worldwide as an important, multidisciplinary aspect of the continuing care of patients with incurable cancer. Symptom control and quality-of-life are of the essence. Various treatment methods are available, and radiotherapy and chemotherapy (used appropriately) are important modalities. Palliative care has to be set against a background of planning, development, and cost-benefit analyses.
Abstract: OBJECTIVE--To obtain baseline information about hospice clinical activity. DESIGN--Survey of hospices by postal questionnaire and telephone interview. SETTING--98 Hospices in the United Kingdom and Republic of Ireland of 111 that had a named matron or senior nurse, including 17 funded by NHS and 81 independent units. PARTICIPANTS--Hospice matrons or nursing sisters in charge, to whom the questionnaire was addressed. RESULTS--Median age of hospices was 7 years, and those built during the past seven years had a median of 12 inpatient beds. All NHS hospices had some input from a medical consultant whereas 12 (15%) of independent units did not. 72 Hospices had home care teams and 12 of 20 of these randomly contacted by telephone provided 24 hour cover. The median number of whole time equivalent nurses was four, but 6 (30%) of teams did not include a doctor. Wide variations were found in discharge rates (range 1-76%) and throughput (1.7-31.8 patients/bed/year). In units with a full time consultant or medical director throughput was greater and more patients had palliative surgery and became organ donors than in units without (45/48 v 38/50 and 45/48 v 25/50, respectively). With the exception of pulmonary function tests and insertion of nasogastric tubes and indwelling epidural catheters, tests and procedures were used by over 90% of hospices, although sometimes the patient had to be transferred elsewhere. CONCLUSIONS--Respondents from units with a full time consultant or medical director were more likely to choose a "technical" description of their unit, such as "a pain relief centre" than those without, who favoured non-technical descriptions. These differences are likely to increase with the appointment of more fully trained consultants in palliative medicine.
Abstract: Hospice care has developed along different paths in Europe, North America, and other cultures. Even within Britain, there is a diversity of hospice models--in-patient units, hospital support teams, day care and home care, with a broad range of clinical services offered. In assessing the clinical results of a hospice service, it is important to bear these differences in mind. Now that more formal, experimental controlled research is being conducted in hospices, there is an opportunity to evaluate quality of life in the same way that has become accepted in clinical cancer trials. The range of evaluations is reviewed, from purely physical assessment to psychological, social, and spiritual problems and the monitoring of bereavement. It is clear that new measurement instruments are needed, particularly for the social and spiritual problems of hospice patients and their families.
Abstract: Ninety five patients (57 with limited disease and 38 with extensive disease) with previously untreated small cell lung cancer were entered into a study of short duration combination chemotherapy with intravenous cyclophosphamide (750 mg/m2) on day 1, adriamycin (40 mg/m2) on day 1, and etoposide VP-16 (100 mg/m2) on days 1, 2, and 3, with the addition on day 10 of methotrexate 50 mg/m2 with folinic acid rescue and vincristine 2 mg. The treatment was repeated on day 22 and only three courses were given. No maintenance chemotherapy was given, though patients with a complete response received radiotherapy (30-40 Gy (3000-4000 rads] to the primary site in most cases. Forty nine patients (86%) with limited disease achieved a response, with 26 (46%) complete remissions. Twenty five patients (66%) with extensive disease had a response, but only eight (21%) had a complete response. Actuarial survival analysis for the whole patient population showed a median survival of 13 months for patients with limited disease and seven months for those with extensive disease. The median survival was 14 months for those patients with limited disease who achieved a complete response, but only 10 months for non-responders. Myelosuppression was the major expression of toxicity. There were three deaths related to treatment and seven patients had febrile episodes during neutropenia that required antibiotics. Mucositis, which was usually mild, occurred in 49% of patients. The primary site was the main site of initial relapse in 56% of the patients who relapsed. Among patients with limited disease who achieved a complete response, relapses at the primary site were less common in those who received radiotherapy (five out of 12) than in those who did not (all eight). The results indicate that this short duration chemotherapy in small cell lung cancer gives response rates and the potential for long term survival similar to those obtained in other series while allowing patients the maximum time free from treatment.
Abstract: This study investigated the use of late dose intensification therapy (LDIT) with cyclophosphamide (180 mg/kg) and VP 16 (1 g/m2) plus autologous bone marrow rescue in 22 patients with small cell lung cancer (SCLC). These patients were selected from a group of 95 patients who received three courses of a five-drug induction regimen comprising cyclophosphamide (750-1000 mg/m2), adriamycin (40 mg/m2), VP 16 (100 mg/m2) for 3 days, methotrexate (50 mg/m2) and vincristine (2 mg) (CAVMO). There were 16 patients with limited disease, 8 of whom were in complete remission (CR) and 8 in partial remission (PR) after the induction therapy. The other 6 patients had extensive disease; 3 of these achieved CR and 3 PR after induction therapy. Of the 11 patients in PR, 5 responded to LDIT; 3 had a further PR, and 2 CR. Subsequent to LDIT radiotherapy 4000 cGy was given to the primary site in 10 of the 22 patients. Since the start of the study, 19 of the 22 patients have relapsed and died (median survival 11 months), while 3 remain alive and in remission at 11, 11, and 24 months. Comparison of the survival of patients receiving LDIT with that of an equivalent group (with respect to staging and response to induction chemotherapy) of patients who received induction chemotherapy alone showed no significant difference. In this study, LDIT following conventional induction therapy in patients with chemosensitive tumours did not improve survival.
Abstract: Reviews of published studies indicate that the incorporation of VP-16 (Vepesid) into combination chemotherapy for small-cell lung cancer may improve overall response rates from 50% to between 65% and 80%. In addition, high-dose VP-16 may yield a higher response rate than that obtained with conventional doses. The West of Scotland Lung Cancer Group has therefore conducted studies to examine the effects of VP-16 both in a combination regimen as induction therapy and (together with high-dose cyclophosphamide) as late intensification therapy in high dose, aimed at preventing relapse in responding patients. Response to induction treatment improved with the addition of VP-16, compared to earlier studies carried out by the group, yielding an overall response rate of 80% for patients with limited disease and 62% for those with extensive disease. Although induction therapy comprised only three courses (lasting 9 weeks), the median response duration of 9.5 months for complete responders and the median survival of 14 months for complete responders (limited disease) were in keeping with those obtained using more prolonged induction therapy. The intensification therapy with high-dose cyclophosphamide and high-dose VP-16, however, yielded no improvement in overall survival in those responding patients who received it compared with those who did not. Radiotherapy following late-dose intensification prevented local tumor recurrence but appeared to have no effect on overall survival. Resistance to VP-16 and other drugs is a possible deterrent to successful therapy in small-cell lung cancer, and it is suggested that research focus on a possible role for calcium channel blockers in circumventing drug resistance.
Abstract: One hundred and five patients with inoperable non-small cell lung cancer were included in a randomized trial comparing the activity of vindesine as a single agent with the combination of vindesine and cisplatin. All patients were previously untreated and the majority (70%) had squamous carcinoma. The overall partial response rates in 88 evaluable patients were 7% for vindesine alone and 33% for the combined regime. There were no complete responders in either arm. The median survival of patients treated with vindesine and cisplatin was 11 months, compared with 4 months in those treated with vindesine alone (P = 0.008). Patients showing a partial or complete response to vindesine and cisplatin survived a median duration of 13 months, compared with 7 months for non-responders (P = 0.03). This survival benefit associated with the combination was particularly apparent for patients with ECOG performance status 0 or 1 (median survival greater than 18 months and 13 months respectively), locoregional disease (median survival 14 months) and squamous cell histology (median survival 13 months). Myelo-suppression was greater with the combination but was not a major treatment problem. Neurotoxicity, which was frequently dose-limiting, was of similar severity in both treatment groups. The results indicate that the combination of vindesine and cisplatin is superior to vindesine alone for remission induction in non-small cell lung cancer and confers a significant survival advantage compared with vindesine alone in patients with favourable prognostic factors.
Abstract: Nabilone, a synthetic cannabinoid, and Prochlorperazine were compared in a double-blind crossover study of 34 patients with lung cancer undergoing a 3-day schedule of chemotherapy with Cyclophosphamide, Adriamycin and Etoposide. Symptom scores were significantly better for patients on nabilone for nausea, retching and vomiting (P less than 0.05). Fewer subjects vomited with nabilone (P = 0.05) and the number of vomiting episodes was lower (P less than 0.05); no patients on nabilone required additional parenteral anti-emetic. More patients preferred nabilone for anti-emetic control (P less than 0.005). Adverse effects common with nabilone were drowsiness (57%), postural dizziness (35%) and lightheadedness (18%). Euphoria was seen in 14% and a "high" in 7%. Erect systolic blood pressure was lower in nabilone patients on Day 1 (P = 0.05) but postural hypotension was a major problem in only 7%. Nabilone is an effective oral anti-emetic drug for moderately toxic chemotherapy, but the range and unpredictability of its side-effects warrant caution in its use.
