Eduardo Bruera

Thalidomide in patients with cachexia due to terminal cancer: preliminary report.

Anorexia/cachexia occurs in approximately 80% of patients with advanced cancer [1]. These patients experience progressive weight loss, and complain of complex symptoms such as anorexia, chronic nausea, fatigue, sleep disorders and decreased sensation of well being. Recently, it has been recognized that cachexia and many of its symptoms are at least partially due to the production of cytokines as a response of the host to neoplastic disease [1, 2]. Tumor necrosis factor-a (TNF-a), a cytokine, is one of the likely mediators of cancer cachexia [2]. Thalidomide, a mild anxiolytic and antiemetic, is capable of reducing the production of TNF-a both in vitro and in vivo [3, 4], and also has anti-angiogenic effects. Because of its ability to reduce the production of TNF-a, thalidomide has been used in AIDS associated cachexia, which is similar to cancer induced cachexia. Thalidomide is very effective in halting and reversing weight loss in AIDS associated cachexia [5, 6]. The usefulness of thalidomide in cancer cachexia has not yet been examined. Therefore, we present our experience with thalidomide in an open study with advanced cancer patients suffering from cachexia.

Plasma and neutrophil fatty acid composition in advanced cancer patients and response to fish oil supplementation

Metabolic demand and altered supply of essential nutrients is poorly characterised in patients with advanced cancer. A possible imbalance or deficiency of essential fatty acids is suggested by reported beneficial effects of fish oil supplementation. To assess fatty acid status (composition of plasma and neutrophil phospholipids) in advanced cancer patients before and after 14 days of supplementation (12±1u2009gu2009day−1) with fish (eicosapentaenoic acid, and docosahexaenoic acid) or placebo (olive) oil. Blood was drawn from cancer patients experiencing weight loss of >5% body weight (n=23). Fatty acid composition of plasma phospholipids and the major phospholipid classes of isolated neutrophils were determined using gas liquid chromatography. At baseline, patients with advanced cancer exhibited low levels (<30% of normal values) of plasma phospholipids and constituent fatty acids and elevated 20:4 n-6 content in neutrophil phospholipids. High n-6/n-3 fatty acid ratios in neutrophil and plasma phospholipids were inversely related to body mass index. Fish oil supplementation raised eicosapentaenoic acid and docosahexaenoic acid content in plasma but not neutrophil phospholipids. 20:4 n-6 content was reduced in neutrophil PI following supplementation with fish oil. Change in body weight during the supplementation period related directly to increases in eicosapentaenoic acid in plasma. Advanced cancer patients have alterations in lipid metabolism potentially due to nutritional status and/or chemotherapy. Potential obstacles in fatty acid utilisation must be addressed in future trials aiming to improve outcomes using nutritional intervention with fish oils.

An International Survey of Undergraduate Medical Education in Palliative Medicine

A 9-item mail survey dealing with availability and characteristics of undergraduate medical education programs in palliative medicine was sent to all medical schools in Canada (16) and the United Kingdom (UK) (30), and 129 randomly selected medical schools in the United States (US) and Western Europe. The overall response rate was 117/175 (67%). The highest percentage of mandatory (required by the university) rotations in palliative medicine was in the UK medical schools (14/22, 64%). Considerably lower numbers were obtained from the other countries: US; 4/37, 11%, Canada; 2/14, 14%, and Western Europe; 8/43, 19% (P = 0.001). Elective rotations in palliative medicine were more readily available in the UK; 18/22, 82% and Canada; 10/14, 71%, compared with the US; 23/37, 62%, and Western Europe; 13/43, 30% (P=0.001). Seventy-two percent (13/18) of UK, 70% (7/10) of Canadian, 59% (16/27) of US, and 9/30 (30%) of Western European medical schools provide educational reading material in palliative medicine (P = 0.014). Case-based learning in small groups and small group discussion were favored by the UK, 14/22 (63%) and 17/22 (77%), respectively, and Canadian medical schools, 8/14 (57%) and 8/14 (57%), respectively (P = 0.176). The number of universities with academic faculty positions for palliative medicine and the median number of positions for the countries were as follows-Canada 8/13 (62%) and 2; UK 12/22 (55%) and 1; US 5/36 (14%) and 1; and Western Europe 9/24 (21%) and 1, respectively (P = 0.001). Besides the UK, mandatory (required) rotations in undergraduate palliative medicine education are lacking in Canadian, US, and Western European medical schools. The median number of 1 academic faculty member per responding medical school is discouraging. In order for undergraduate and postgraduate medical education in palliative medicine to improve, the number of both educational programs and faculty members will need to be increased.

Testosterone replacement for fatigue in hypogonadal ambulatory males with advanced cancer: a preliminary double-blind placebo-controlled trial

BackgroundUncontrolled studies show fatigue, anorexia, depression, and mortality are associated with low testosterone in men with cancer. Testosterone replacement improves quality of life and diminishes fatigue in patients with non-cancer conditions. The primary objective was to evaluate the effect of testosterone replacement on fatigue in hypogonadal males with advanced cancer, by the Functional Assessment of Chronic Illness Therapy-Fatigue subscale (FACIT-Fatigue) at day 29.MethodsThis is a randomized, double-blinded placebo-controlled trial. Outpatients with advanced cancer, bioavailable testosterone (BT) <70xa0ng/dL and fatigue score >3/10 on the Edmonton Symptom Assessment Scale were eligible. Intra-muscular testosterone or sesame seed oil placebo was administered every 14xa0days to achieve BT levels 70–270xa0ng/dL.ResultsSixteen placebo and 13 testosterone-treated subjects were evaluable. No statistically significant difference was found for FACIT-fatigue scores between arms (−2u2009±u200912 for placebo, 4u2009±u20098 for testosterone, pu2009=u20090.11). Sexual Desire Inventory score (pu2009=u20090.054) and performance status (pu2009=u20090.02) improved in the testosterone group. Fatigue subscale scores were significantly better (pu2009=u20090.03) in those treated with testosterone by day 72.ConclusionsFour weeks of intramuscular testosterone replacement in hypogonadal male patients with advanced cancer did not significantly improve quality of life. Larger studies of longer duration are warranted.

A randomized controlled trial of local injections of hyaluronidase versus placebo in cancer patients receiving subcutaneous hydration

BACKGROUNDnMost cancer patients develop reduced oral intake or dehydration before death. Subcutaneous hydration (SCH) can be safe and effective. SCH is frequently administered using hyaluronidase to improve fluid absorption. The objective of this study was to determine the effects of hyaluronidase on patient comfort during bolus SCH.nnnPATIENTS AND METHODSnTwenty-one cancer patients requiring parenteral hydration were administered a 500 cc bolus of two-thirds dextrose (5%) and one-third normal saline solution subcutaneously at 08:00 and 16:00 hours during day 1 and day 2. On day 1 patients were randomized on a double-blind basis to receive 150 units of hyaluronidase versus placebo as a bolus into the site of infusion immediately before starting each one-hour infusion. During day 2 patients were crossed over to receive the alternate treatment at a new infusion site. Visual analogue scales (0 = best, 100 = worst) for pain and swelling at the infusion site were completed by each patient. In addition, investigators blindly assessed the site of infusion for the presence of edema, rash, and leakage.nnnRESULTSnNo significant differences were observed for pain, swelling, edema, rash or leakage between the placebo and the hyaluronidase scores. After completion of the two days of the study, patients blindly chose hyaluronidase in 1 (5%) case, placebo in 5 (24%) cases, and no preference in 15 (71%) cases (P < 0.01). There was no treatment or interaction effect for pain, except for a period effect (P = 0.045) for the morning bolus administration. There were no treatment, period, or interaction effects for any of the other variables.nnnCONCLUSIONSnOur results suggest that hyaluronidase is not necessary for routine bolus SCH. It may still be useful for a minority of patients who are not able to tolerate infusion well due to swelling or pain.

Do we need palliative care audit in developing countries

Modern palliative care developed in the UK in the 1960s as a response to the unmet needs of terminally ill patients and their families. This initially British movement soon became global; currently, most regions in the world and over 90 countries have palliative care initiatives at different stages of development. The principles of impeccable management of physical, psychological, and social symptoms in patients and families, and attention to bereavement and spiritual concerns are consistent around the world. However, the socioeconomic and cultural environments, the patients and families, the prevailing diseases, and the health care systems, including health care professionals, technology, and drugs, differ enormously. Therefore, the development of palliative care has occurred at a different pace and with different characteristics in different regions.

The frequency of missed delirium in patients referred to palliative care in a comprehensive cancer center

BackgroundDelirium is one of the most common neuropsychiatric complications in advanced cancer patients with a frequency of up to 85xa0% before death. It is associated with adverse clinical outcomes such as increased morbidity and mortality as well as significant family and patient distress. The aim of our study is to determine at the frequency of missed delirium (MD) and identify factors associated with MD.MethodsSeven hundred seventy-one consecutive palliative care inpatient consults from August 1, 2009 to January 31, 2010 were reviewed. Demographics, Memorial Delirium Assessment Scale (MDAS), Edmonton Symptom Assessment Scale (ESAS), primary referral symptom, Eastern Cooperative Oncology Group (ECOG), and physician diagnosis of delirium were collected along with delirium etiology, subtype, and reversibility. Delirium was diagnosed with a MDAS score of ≥7 or by a palliative medicine specialist using Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Text Revision (DSM-IV TR) Criteria. MD was reported in those patients found to have delirium by the palliative medicine specialists but were referred by the primary team for other reasons besides delirium. Chi-squared test and Wilcoxon-Mann-Whitney test were used to examine the difference on measurements among or between different groups. Univariate logistic regression model was applied to assess for associations for MD.ResultsTwo hundred fifty-two (33xa0%) had a diagnosis of delirium by the palliative medicine specialist. One hundred fifty-three (61xa0%) were missed by the primary referring team. Females comprised 53xa0% (nu2009=u200981), white 62xa0% (nu2009=u200995), and pain was the most common referral symptom (nu2009=u200977, 50xa0%). Hypoactive delirium was the most common subtype of delirium in MD (nu2009=u200947, 63xa0%). Opioid-related delirium was the most common etiology of MD (nu2009=u200947, 31xa0%). Patients referred for pain were more likely to have MD (odds ratio (OR)u2009=u20092.57, pu2009=u20090.0109). Of the 82 patients with delirium that was reversed, 67xa0% (nu2009=u200955) had a diagnosis of MD.ConclusionSixty-one percent of patients with a diagnosis of delirium by a palliative care specialist were missed by the primary referring team. Patients with MD were frequently referred for pain. Universal screening of cancer patients for delirium is recommended.

European Society for Medical Oncology (ESMO) position paper on supportive and palliative care

Oncology has come a long way in addressing patients quality of life, together with developing surgical, radio-oncological and medical anticancer therapies. However, the multiple and varying needs of patients are still not being met adequately as part of routine cancer care. Supportive and palliative care interventions should be integrated, dynamic, personalised and based on best evidence. They should start at the time of diagnosis and continue through to end-of-life or survivorship. ESMO is committed to excellence in all aspects of oncological care during the continuum of the cancer experience. Following the 2003 ESMO stand on supportive and palliative care (Cherny N, Catane R, Kosmidis P. ESMO takes a stand on supportive and palliative care. Ann Oncol 2003; 14(9): 1335-1337), this position paper highlights the evolving and growing gap between the needs of cancer patients and the actual provision of care. The concept of patient-centred cancer care is presented along with key requisites and areas for further work.

Complementary therapy use : a survey of community- and hospital-based patients with advanced cancer

Increasing numbers of patients are making use of complementary therapies.1 A systematic review of complementary therapy use by cancer patients found an average prevalence of 31%.2 Common reasons for use, identified by patients, include to cure their cancer, improve survival or improve symptoms, and pressure from family and friends.3–8 Use of complementary therapies may also be fostered by negative experiences with the cancer patient’s health-care provider(s) and a poor response or side-effects generated by conventional oncological, and to some degree, palliative care treatments. Despite a lack of scientific evidence to substantiate the benefits of many of these therapies, many patients acknowledge some degree of beneficial effect.3,5 This paper presents the results of a face-to-face survey dealing with complementary therapy use in 104 consecutive advanced cancer patients in the community and 50 consecutive advanced cancer patients in a tertiary palliative care unit.

The Association Among Hypogonadism, Symptom Burden, and Survival in Male Patients with Advanced Cancer

A high frequency of hypogonadism has been reported in male patients with advanced cancer. The current study was performed to evaluate the association between low testosterone levels, symptom burden, and survival in male patients with cancer.