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.

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.

The ALERT-B questionnaire: A screening tool for the detection of gastroenterological late effects after radiotherapy for prostate cancer.

There is an increasing need to measure treatment-related side effects in normal tissues following cancer therapy. The ALERT-B (Assessment of Late Effects of RadioTherapy - Bowel) questionnaire is a screening tool that is composed of four items related specifically to bowel symptoms. Those patients that respond with a "yes" to any of these items are referred on to gastroenterologist in order to improve the long-term consequences of these side effects of radiological treatment. Here we wish to test the ability of this questionnaire to identify these subsequent gastroenterological complications by tracking prostate cancer patients that were positive with respect to ALERT-B. We also carry out receiver-operator curve (ROC) analysis for baseline data for an overall ALERT-B questionnaire score with respect to subscale data for the Gastrointestinal Symptom Rating Scale (GSRS) and the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire. 84.4% and 95.7% of patients identified by the ALERT-B questionnaire demonstrated complications diagnosed at 6 and 12 months post-treatment, respectively. ROC curve analysis of baseline data showed that ALERT-B detected clinically relevant levels of side effects established at baseline by the GSRS diarrhoea subscale (AUC = 0.867, 95% CI = 0.795 to 0.926) and at the minimally important level of side effects for the EPIC bowel subscale (AUC = 0.765, 95% CI = 0.617 to 0.913). These results show that ALERT-B provides a simple and effective screening tool for identifying gastroenterological complications after treatment for prostate cancer.

The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology.

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.

New approaches to pain control in patients with cancer.

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.

Recent clinical trials of pain control: impact on quality of life.

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.

The EORTC QLQ-LC13: a modular supplement to the EORTC Core Quality of Life Questionnaire (QLQ-C30) for use in lung cancer clinical trials. EORTC Study Group on Quality of Life.

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.

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.

The role of VP-16 in the treatment of small-cell lung cancer: studies of the West of Scotland Lung Cancer Group.

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.

High-dose cyclophosphamide and VP 16 as late dosage intensification therapy for small cell carcinoma of lung.

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.

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.

Transdermal fentanyl versus sustained-release oral morphine in cancer pain: preference, efficacy, and quality of life. The TTS-Fentanyl Comparative Trial Group.

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.

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.

Measuring quality of life in hospice care.

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.

Supportive care for patients with gastrointestinal cancer.

BACKGROUND: Supportive care has traditionally been given to optimise the comfort of patients and their ability to function, as well as to minimise the side-effects of anti-cancer treatments. The scope of modern comprehensive supportive care however is broadening and covers not only specific palliative treatment but non-tumour specific treatment such as social, psychological and spiritual support. In oncology, best supportive care (BSC) has been used as a comparator arm of randomised controlled trials in chemotherapy. However the BSC arm is usually not well defined and its evaluation is therefore difficult because of the heterogeneity of the definitions. A systematic review was undertaken of the evidence from all RCTs of gastrointestinal cancers (includes gastrointestinal/gastric, colorectal/colon cancer but excludes pancreatic cancer trials) which include a BSC/SC arm. OBJECTIVES: 1. To examine the effectiveness/outcomes of best supportive care interventions versus cancer therapies for gastrointestinal cancer trials;2. To determine whether trials containing best supportive care include a definition of this. SEARCH STRATEGY: Electronic databases, grey literature sources, citation searching and reference checking, handsearches of journals and discussion with experts were used to identify potentially eligible trials from both published and unpublished sources. SELECTION CRITERIA: RCTs comparing BSC/SC versus anticancer therapies in patients with gastrointestinal cancers. DATA COLLECTION AND ANALYSIS: Four RCTs were found and reviewed. Because of the heterogeneity of studies, a meta-analysis was not attempted. Data was extracted from the included papers and the quality of each included study was assessed using the Jadad 1996 and Rinck 1997 methods of assessing the quality of RCTs. MAIN RESULTS: Data from four trials (483 patients) were included. Due to the heterogeneity of studies (in terms of populations studied, the interventions used, the variety of outcomes and assessments used) it was not possible to make direct comparisons between the studies. The primary outcome in all four trials was survival, in spite of patients with advanced/metastatic gastrointestinal cancer having a poor prognosis, and the interventions being primarily palliative. REVIEWERS' CONCLUSIONS: Overall the results show that for most of the trials included in this review, certain forms of chemotherapy plus supportive care improve both survival and quality of life in patients with gastrointestinal cancer (gastric and colorectal cancers) compared to receiving supportive care alone. Trials involving BSC/SC in patients with advanced gastrointestinal cancer require careful evaluation. Oncologists and researchers alike should strive for improvements in trial design and reporting. Future trials should focus on clearer definitions of supportive care. The EORTC definition of supportive care can be used as a guide. BSC/SC trials should use standardised validated outcome measures for symptom control, quality of life, toxicity and other useful palliative measures.

Evaluation of clinical efficacy of new medical treatments in advanced colorectal cancer. Results of a workshop organized by the EORTC GITCCG. European Organization for Research and Treatment of Cancer. Gastrointestinal Tract Cancer Cooperative Group.

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.

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.

What do hospices do? A survey of hospices in the United Kingdom and Republic of Ireland.

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.