Feasibility of early multimodal interventions for elderly patients with advanced pancreatic and non-small-cell lung cancer.

BACKGROUND: Combinations of exercise and nutritional interventions might improve the functional prognosis for cachectic cancer patients. However, high attrition and poor compliance with interventions limit their efficacy. We aimed to test the feasibility of the early induction of new multimodal interventions specific for elderly patients with advanced cancer Nutrition and Exercise Treatment for Advanced Cancer (NEXTAC) programme. METHODS: This was a multicentre prospective single-arm study. We recruited 30 of 46 screened patients aged ≥70 years scheduled to receive first-line chemotherapy for newly diagnosed, advanced pancreatic, or non-small-cell lung cancer. Physical activity was measured using pedometers/accelerometer (Lifecorder® , Suzuken Co., Ltd., Japan). An 8 week educational intervention comprised three exercise and three nutritional sessions. The exercise interventions combined home-based low-intensity resistance training and counselling to promote physical activity. Nutritional interventions included standard nutritional counselling and instruction on how to manage symptoms that interfere with patient's appetite and oral intake. Supplements rich in branched-chain amino acids (Inner Power® , Otsuka Pharmaceutical Co., Ltd., Japan) were provided. The primary endpoint of the study was feasibility, which was defined as the proportion of patients attending ≥4 of six sessions. Secondary endpoints included compliance and safety. RESULTS: The median patient age was 75 years (range, 70-84). Twelve patients (40%) were cachectic at baseline. Twenty-nine patients attended ≥4 of the six planned sessions (96.7%, 95% confidence interval, 83.3 to 99.4). One patient dropped out due to deteriorating health status. The median proportion of days of compliance with supplement consumption and exercise performance were 99% and 91%, respectively. Adverse events possibly related to the NEXTAC programme were observed in five patients and included muscle pain (Grade 1 in two patients), arthralgia (Grade 1 in one patient), dyspnoea on exertion (Grade 1 in one patient), and plantar aponeurositis (Grade 1 in one patient). CONCLUSIONS: The early induction of multimodal interventions showed excellent compliance and safety in elderly patients with newly diagnosed pancreatic and non-small-cell lung cancer receiving concurrent chemotherapy. We are now conducting a randomized phase II study to measure the impact of these interventions on functional prognosis.

Cancer cachexia: rationale for the MENAC (Multimodal-Exercise, Nutrition and Anti-inflammatory medication for Cachexia) trial.

Cancer cachexia is a multifactorial syndrome characterised by an ongoing loss of skeletal muscle mass that cannot be fully reversed by conventional nutritional support alone. Cachexia has a high prevalence in cancer and a major impact on patient physical function, morbidity and mortality. Despite the consequences of cachexia, there is no licensed treatment for cachexia and no accepted standard of care. It has been argued that the multifactorial genesis of cachexia lends itself to therapeutic targeting through a multimodal treatment. Following a successful phase II trial, a phase III randomised controlled trial of a multimodal cachexia intervention is under way. Termed the MENAC trial (Multimodal-Exercise, Nutrition and Anti-inflammatory medication for Cachexia), this intervention is based on evidence to date and consists of non-steroidal anti-inflammatory drugs and eicosapentaenoic acid to reduce inflammation, a physical exercise programme using resistance and aerobic training to increase anabolism, as well as dietary counselling and oral nutritional supplements to promote energy and protein balance. Herein we describe the development of this trial. TRIAL REGISTRATION NUMBER: NCT02330926.

Relationship Between Spirituality, Meaning in Life, Psychological Distress, Wish for Hastened Death, and Their Influence on Quality of Life in Palliative Care Patients.

CONTEXT: Spiritual, existential, and psychological issues represent central components of quality of life (QOL) in palliative care. A better understanding of the dynamic nature underlying these components is essential for the development of interventions tailored to the palliative context. OBJECTIVES: The aims were to explore 1) the relationship between spirituality, meaning in life, wishes for hastened death and psychological distress in palliative patients and 2) the extent to which these nonphysical determinants influence QOL. METHODS: A cross-sectional study involving face-to-face interviews with Swiss palliative patients was performed, including the Schedule for Meaning in Life Evaluation (SMILE), the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp), the Idler Index of Religiosity (IIR), the Hospital Anxiety and Depression Scale (HADS), and the Schedule of Attitudes toward Hastened Death (SAHD). QOL was measured with a single-item visual analogue scale (0-10). RESULTS: Two hundred and six patients completed the protocol (51.5% female; mean age = 67.5 years). The results indicated a significant negative relationship between FACIT-Sp/SMILE and HADS total scores (P = 0.000). The best model for QOL explained 32.8% of the variance (P = 0.000) and included the FACIT-Sp, SMILE, and SAHD total scores, the IIR "private religiosity" score, as well as the HADS "depression" score. CONCLUSION: Both spiritual well-being and meaning in life appear to be potential protective factors against psychological distress at the end of life. Since nonphysical determinants play a major role in shaping QOL at the end of life, there is a need for the development of meaning-oriented and spiritual care interventions tailored to the fragility of palliative patients.

Dying is a transition.

PURPOSE: End-of-life care is designed as response to patients' verbally communicated needs. The concept of dying as a process would allow us to improve care. This concept may combine the needs of the dying, their outburst of emotions, gradual maturation, family processes, acute problems such as decreasing independence, with their inner experience and transformation of perception. In this study we explored dying patients' mode of perception, and deeper reasons for anxiety and existential suffering. METHODS: Dying inpatients of a major cancer centre treated by an interdisciplinary team were eligible. Psychotherapy records of cancer patients (course, reactions, discussions with nurses and physicians) provided the data. Participant observation and Interpretative Phenomenological Analysis (IPA) was applied. RESULTS: Our data (pilot study N=80/follow-up-study N=600) suggest that patients undergo transition into another state of consciousness beyond anxiety, ego, and pain. Transition appears to have three stages. Anxiety, struggle, denial/acceptance, family processes, and maturation (ie, finding meaning and dignity, coping with trauma) may depend on the transitional process and also hinder or facilitate this transitional process. CONCLUSIONS: Understanding dying as transition may induce a radical reinterpretation of what patients need.

[Anemia caused by cancer in the context of palliative care]. / Tumoranämie im palliativen Kontext.

Tumor anemia is very common in patients with cancer. The causes are very diverse and the parameter value depends on several factors. If this however develops to be symptomatic it may adversely impact health related quality of life. Erythropoietin or blood transfusion provides options for treatment. However, these are not always uneventful. There could also be a lack of response to Erythropoietin. This case report describes the complexity of tumor anemia. It also includes a more detailed discussion on the Fatigue Syndrome, which is one of the most common symptoms of patients with cancer. In the context of palliative care there is often the question of alternatives for improving the quality of patients life. Some kinds of treatment may also cause the opposite effect. A multidimensional assessment should help to approach this difficult issue and to find ways for a meaningful treatment of the symptoms of anemia.

Palliative cancer care a decade later: accomplishments, the need, next steps -- from the American Society of Clinical Oncology.

PURPOSE: In 1998, the American Society of Clinical Oncology (ASCO) published a special article regarding palliative care and companion recommendations. Herein we summarize the major accomplishments of ASCO regarding palliative cancer and highlight current needs and make recommendations to realize the Society's vision of comprehensive cancer care by 2020. METHODS: ASCO convened a task force of palliative care experts to assess the state of palliative cancer care in the Society's programs. We reviewed accomplishments, assessed current needs, and developed a definition of palliative cancer. Senior ASCO members and the Board of Directors reviewed and endorsed this article for submission to Journal of Clinical Oncology. RESULTS: Palliative cancer care is the integration into cancer care of therapies that address the multiple issues that cause suffering for patients and their families and impact their life quality. Effective provision of palliative cancer care requires an interdisciplinary team that can provide care in all patient settings, including outpatient clinics, acute and long-term care facilities, and private homes. Changes in current policy, drug availability, and education are necessary for the integration of palliative care throughout the experience of cancer, for the achievement of quality improvement initiatives, and for effective palliative cancer care research. CONCLUSION: The need for palliative cancer care is greater than ever notwithstanding the strides made over the last decade. Further efforts are needed to realize the integration of palliative care in the model and vision of comprehensive cancer care by 2020.

Prevention of docetaxel- or paclitaxel-associated taste alterations in cancer patients with oral glutamine: a randomized, placebo-controlled, double-blind study.

Taste alteration (dysgeusia), an underrecognized toxicity associated with taxane-based chemotherapy (TaxCh), lacks standard treatment. We investigated prevention of dysgeusia with oral glutamine in patients undergoing first-time TaxCh. Adult patients were randomized to receive either 30 g/day glutamine or placebo (maltodextrin) from day 1 of TaxCh. Dysgeusia was measured daily with a visual analogue scale (VAS). On each chemotherapy cycle, objective (sour, sweet, salty, bitter) and subjective (four-category scale) taste and toxicity (National Cancer Institute Common Toxicity Criteria, v.3) were assessed. Stomatitis and zinc deficiency were treated. For primary outcomes, repeated dysgeusia scores were analyzed with a linear mixed model. Repeated data on each objective or subjective taste item were analyzed with a generalized estimating equation. Of 52 patients randomized, 41 completed treatment (median study duration, 74 days). At baseline, the glutamine (n = 21) and placebo (n = 20) groups were comparable for age (64 years), gender (32% men), tumor types, chemotherapy (docetaxel, 44%; paclitaxel, 56%), schedule (weekly, 78%; 3-weekly, 22%), treatment intention (15% adjuvant), dysgeusia (VAS, 11/100), and taste recognition (88%). Twenty-four patients had peripheral neuropathy grades 1-2; none had grade 3. Glutamine and placebo were not different for maximal dysgeusia and increase from baseline, with an insignificant linear time effect. Separate subgroup analyses for patients with baseline dysgeusia < or =11 or >11 did not alter the results. Objective or subjective taste tests were not different, neither were adverse events. Compared with placebo, oral glutamine did not prevent or decrease subjective taste disturbances or altered taste perception associated with TaxCh. The role of glutamine in supportive care of taxane-associated dysgeusia seems limited.

Appraisal of current and experimental approaches to the treatment of cachexia.

PURPOSE OF REVIEW: To summarize the latest clinical developments in pharmacological interventions for primary cachexia. RECENT FINDINGS: New orexigenic interventions that interfere with the central regulation of food intake are expected to be derived from the group of melanocortin receptor antagonists and ghrelin-mimetic agents. Emerging are muscle agents, including ubiquitin-proteasome system inhibitors, antimyostatin drugs, dystrophin, and beta2-adrenergic agonists. Results from anabolic steroids and angiotensin-II inhibitors are awaited. Recent data support insulin tackling fat metabolism. Branched-chain amino acids, N-3 fatty acids and conjugated linoleic acid are nutritional supplements that show potential. Adenosine 5'-triphosphate expands to related compounds (including ubiquinone). No breakthrough has occurred with the use of anti-inflammatory agents. Moreover, nonsteroidal anti-inflammatory drugs and thalidomide merit definitive studies. Presently modern anticytokine treatments lack proof of broad effectiveness. Some NF-kappaB inhibitors hold early promise. Melatonin requires placebo-controlled trials before recommendations on clinical use. Oxidative stress probably contributes to muscle wasting. L-Carnitine and other antioxidants appear promising. Anticancer treatments designed as anticachexia interventions remain scarce. SUMMARY: A number of promising new agents are in development but are not yet regarded as standard of care. This void calls for well-designed, proof-of-concept studies followed by placebo-controlled, randomized trials.

Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group.

PURPOSE: To compare the effects of cannabis extract (CE), delta-9-tetrahydrocannabinol (THC), and placebo (PL) on appetite and quality of life (QOL) in patients with cancer-related anorexia-cachexia syndrome (CACS). PATIENTS AND METHODS: Adult patients with advanced cancer, CACS, weight loss (> or = 5% over 6 months), and Eastern Cooperative Oncology Group (ECOG) performance status (PS) < or = 2 were randomly assigned (2:2:1) to receive CE (standardized for 2.5 mg THC and 1 mg cannabidiol) or THC (2.5 mg) or PL orally, twice daily for 6 weeks. Appetite, mood, and nausea were monitored daily with a visual analog scale (VAS); QOL was assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (composite score: questions 29 and 30). Cannabinoid-related toxicity was assessed every 2 weeks. RESULTS: Of 289 patients screened, 243 were randomly assigned and 164 (CE, 66 of 95 patients; THC, 65 of 100 patients; and PL, 33 of 48 patients) completed treatment. At baseline, groups were comparable for age (mean, 61 years), sex (54% men), weight loss (32% > or = 10%), PS (13% ECOG = 2), antineoplastic treatment (50%), appetite (mean VAS score, 31/100 mm), and QOL (mean score, 30/100). Intent-to-treat analysis showed no significant differences between the three arms for appetite, QOL, or cannabinoid-related toxicity. Increased appetite was reported by 73%, 58%, and 69% of patients receiving CE, THC, or PL, respectively. An independent data review board recommended termination of recruitment because of insufficient differences between study arms. CONCLUSION: CE at the oral dose administered was well tolerated by these patients with CACS. No differences in patients' appetite or QOL were found either between CE, THC, and PL or between CE and THC at the dosages investigated.

Impact of a half-day multidisciplinary symptom control and palliative care outpatient clinic in a comprehensive cancer center on recommendations, symptom intensity, and patient satisfaction: a retrospective descriptive study.

To characterize a new, one-stop multidisciplinary palliative care (MD) clinic which offers standardized multidisciplinary assessment, specific care recommendations, patient and family education, and on-site counseling, we retrospectively compared the assessments of 138 consecutive patients with advanced cancer referred to the MD clinic and 77 patients referred to a traditional pain and symptom management (PSM) clinic. The two groups were similar in tumor type, demographics, and symptom distress. The MD clinic team (physicians; nurses; pharmacists; physical, speech, and occupational therapists; social workers; chaplains; nutritionists; psychiatric nurse practitioner) delivered 1,066 non-physician recommendations (median 4 per patient, range 0-37). The PSM clinic team made no non-physician recommendations, but referred 14 patients to other medical specialists. In 80 (58%) MD-clinic patients with follow-up 9 days (median) after assessment, significant improvement was observed in pain, nausea, depression, anxiety, sleep, dyspnea, and well-being, but not in fatigue, anorexia, or drowsiness. In 83 patients interviewed after the MD clinic, satisfaction was rated as excellent (5 out of 5) in 86-97% of seven areas. Assessment at an MD clinic results in a high number of patient care recommendations, improved symptoms, and high levels of patient satisfaction.

A randomized controlled trial of supplemental oxygen versus air in cancer patients with dyspnea.

CONTEXT: The symptomatic benefits of oxygen in patients with cancer who have nonhypoxic dyspnea are not well defined. OBJECTIVE: To determine whether or not oxygen is more effective than air in decreasing dyspnea and fatigue and increasing distance walked during a 6-minute walk test. PATIENTS AND METHODS: Patients with advanced cancer who had no severe hypoxemia (i.e., had an O2 saturation level of > or = 90%) at rest and had a dyspnea intensity of > or = 3 on a scale of 0-10 (0 = no shortness of breath, 10 = worst imaginable shortness of breath) were recruited from an outpatient thoracic clinic at a comprehensive cancer center. This was a double-blind, randomized crossover trial. Supplemental oxygen or air (5 L/min) was administered via nasal cannula during a 6-minute walk test. The outcome measures were dyspnea at 3 and 6 minutes, fatigue at 6 minutes, and distance walked. We also measured oxygen saturation levels at baseline, before second treatment phase, and at the end of study. RESULTS: In 33 evaluable patients (31 with lung cancer), no significant differences between treatment groups were observed in dyspnea, fatigue, or distance walked (dyspnea at 3 minutes: P = 0.61; dyspnea, fatigue, and distance walked at 6 minutes: P = 0.81, 0.37, and 0.23, respectively). CONCLUSIONS: Currently, the routine use of supplemental oxygen for dyspnea during exercise in this patient population cannot be recommended.

Effect of fish oil on appetite and other symptoms in patients with advanced cancer and anorexia/cachexia: a double-blind, placebo-controlled study.

PURPOSE: To determine whether high doses of fish oil, administered over 2 weeks, improve symptoms in patients with advanced cancer and decreased weight and appetite. PATIENTS AND METHODS: Sixty patients were randomly assigned to fish oil capsules or placebo. Appetite, tiredness, nausea, well-being, caloric intake, nutritional status, and function were prospectively assessed at days 1 and 14. RESULTS: The baseline weight loss was 16 +/- 11 and 16 +/- 8 kg in the fish oil (n = 30) and placebo (n = 30) group respectively, whereas the baseline appetite (0 mm = best and 10 mm = worst) was 58 +/- 24 mm and 67 +/- 19 mm, respectively (P = not significant). The mean daily dose was 10 +/- 4 (fish oil group) and 9 +/- 3 (placebo group) capsules, which provided 1.8 g of eicosapentaenoic acid and 1.2 g of docosahexaenoic acid in the fish oil group. No significant differences in symptomatic or nutritional parameters were found (P <.05), and there was no correlation between changes in different variables between days 1 and 14 and the fish oil doses. Finally, the majority of the patients were not able to swallow more than 10 fish oil capsules per day, mainly because of burping and aftertaste. CONCLUSION: Fish oil did not significantly influence appetite, tiredness, nausea, well-being, caloric intake, nutritional status, or function after 2 weeks compared with placebo in patients with advanced cancer and loss of both weight and appetite.