Shalini Dalal

Reduction of Cancer-Related Fatigue With Dexamethasone: A Double-Blind, Randomized, Placebo-Controlled Trial in Patients With Advanced Cancer

PURPOSE Cancer-related fatigue (CRF) is the most common symptom in patients with advanced cancer. The primary objective of this prospective, randomized, double-blind, placebo-controlled study was to compare the effect of dexamethasone and placebo on CRF. PATIENTS AND METHODS Patients with advanced cancer with ≥ three CRF-related symptoms (ie, fatigue, pain, nausea, loss of appetite, depression, anxiety, or sleep disturbance) ≥ 4 of 10 on the Edmonton Symptom Assessment Scale (ESAS) were eligible. Patients were randomly assigned to either dexamethasone 4 mg or placebo orally twice per day for 14 days. The primary end point was change in the Functional Assessment of Chronic Illness-Fatigue (FACIT-F) subscale from baseline to day 15. Secondary outcomes included anorexia, anxiety, depression, and symptom distress scores. RESULTS A total of 84 patients were evaluable (dexamethasone, 43; placebo, 41). Mean (± standard deviation) improvement in the FACIT-F subscale at day 15 was significantly higher in the dexamethasone than in the placebo group (9 [± 10.3] v 3.1 [± 9.59]; P = .008). The improvement in FACIT-F total quality-of-life scores was also significantly better for the dexamethasone group at day 15 (P = .03). The mean differences in the ESAS physical distress scores at day 15 were significantly better for the dexamethasone group (P = .013, respectively). No differences were observed for ESAS overall symptom distress (P = .22) or psychological distress score (P = .76). Frequency of adverse effects was not significantly different between groups (41 of 62 v 44 of 58; P = .14). CONCLUSION Dexamethasone is more effective than placebo in improving CRF and quality of life in patients with advanced cancer.

Parenteral Hydration in Patients With Advanced Cancer: A Multicenter, Double-Blind, Placebo-Controlled Randomized Trial

PURPOSE The vast majority of patients with cancer at the end of life receive parenteral hydration in hospitals and no hydration in hospice, with limited evidence supporting either practice. In this randomized controlled trial, we determined the effect of hydration on symptoms associated with dehydration, quality of life, and survival in patients with advanced cancer. PATIENTS AND METHODS We randomly assigned 129 patients with cancer from six hospices to receive parenteral hydration (normal saline 1 L per day) or placebo (normal saline 100 mL per day) daily over 4 hours. The primary outcome was change in the sum of four dehydration symptoms (fatigue, myoclonus, sedation and hallucinations, 0 = best and 40 = worst possible) between day 4 and baseline. Secondary outcomes included Edmonton Symptom Assessment Scale (ESAS), Memorial Delirium Assessment Scale (MDAS), Nursing Delirium Screening Scale (NuDESC), Unified Myoclonus Rating Scale (UMRS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Dehydration Assessment Scale, creatinine, urea, and overall survival. Intention-to-treat analysis was conducted to examine the change by day 4 ± 2 and day 7 ± 2 between groups. RESULTS The hydration (n = 63) and placebo (n = 66) groups had similar baseline characteristics. We found no significant differences between the two groups for change in the sum of four dehydration symptoms (-3.3 v -2.8, P = .77), ESAS (all nonsignificant), MDAS (1 v 3.5, P = .084), NuDESC (0 v 0, P = .13), and UMRS (0 v 0, P = .54) by day 4. Results for day 7, including FACIT-F, were similar. Overall survival did not differ between the two groups (median, 21 v 15 days, P = .83). CONCLUSION Hydration at 1 L per day did not improve symptoms, quality of life, or survival compared with placebo.

Comparison of symptom burden among patients referred to palliative care with hematologic malignancies versus those with solid tumors.

BACKGROUND Patients with hematologic malignancies have reduced and later access to palliative care services (APCS) than do those with solid tumors. It is unclear whether these patients develop a high symptom burden at the end of life that requires special palliative care interventions. The purposes of this retrospective study were to determine whether symptoms are less severe in patients with hematologic than in those with solid malignancies on APCS and whether symptom severity is associated with early APCS. METHODS We studied the records of consecutive patients with hematologic and solid malignancies at their first palliative care consultation (PC1). We collected information about demographics, cancer type, date of PC1, and the interval from PC1 to death (PC1-D). We reviewed the charts for the Edmonton Symptoms Assessment System (ESAS) and presence of delirium. RESULTS We included 250 patients (125 with each type of malignancy). Median pain and drowsiness were 4 (3-5) and 7 (5-10) among hematologic compared to 5 (4-6, p=0.043) and 5 (3-6, p=0.0008) among patients with solid malignancies, respectively. Delirium was detected in 51 of 125 (41%) hematologic versus 20 of 125 (16%) solid (p=0.0001). Median PC1-D was 13 days for hematologic versus 46 days for solid (p=0.0001). There was no correlation between PC1-D and pain (r= -0.117, p=0.4 for hematologic and r=0.09, p=0.37 for solid), dyspnea (r= -0.02, p=0.85 for hematologic and r=0.09, p=0.42 for solid) or the Symptom Distress Score (r= -0.047, p=0.72 for hematologic and r= -0.093, p=0.32 for solid). CONCLUSIONS Hematologic patients had increased delirium and drowsiness and later APCS The overall symptom severity was similar in both groups of patients and did not correlate with early APCS. Future prospective studies are needed to better define APCS patterns in this group.

Relationships among body mass index, longitudinal body composition alterations, and survival in patients with locally advanced pancreatic cancer receiving chemoradiation: a pilot study.

CONTEXT In pancreatic cancer, the presence of obesity or weight loss is associated with higher mortality. OBJECTIVES To explore the relationships among body mass index, longitudinal body composition alterations, and clinical outcomes in pancreatic cancer patients. METHODS Records of 41 patients with inoperable locally advanced pancreatic cancer who participated in a prospective chemoradiation study were reviewed. Body composition was analyzed from two sets of computed tomography images obtained before and after radiation treatment (median interval 104 days). RESULTS Median age was 59 years and 56% of patients were female. Twenty-four (59%) patients were either overweight (22%) or obese (37%). Sarcopenia was present in 26 (63%) patients. At follow-up, weight loss was experienced by 33 (81%) patients. The median losses (%) before and after treatment were weight 5% (P<0.001), skeletal muscle (SKM) 4% (P=0.003), visceral adipose tissue (VAT) 13% (P<0.001), and subcutaneous adipose tissue 11% (P=0.002). SKM loss positively correlated with age (P=0.03), baseline body mass index (P<0.001), and VAT (P=0.04) index. Obese patients experienced higher losses in weight (P=0.009), SKM (P=0.02), and VAT (P=0.02). Median survival was 12 months. In univariate analysis, age, baseline obesity, sarcopenic obesity, and losses (%) in weight, SKM, and VAT were associated with worse survival. In multivariate analysis, only age (hazard ratio=1.033, P=0.04) and higher VAT loss (hazard ratio=2.6 and P=0.03) remained significant. CONCLUSION Our preliminary findings suggest that obese patients experience higher losses in weight, SKM, and VAT, which may contribute to poorer survival in these patients.

Clinical Outcomes and Contributors to Weight Loss in a Cancer Cachexia Clinic

BACKGROUND Cancer cachexia is considered intractable, with few therapeutic options. Secondary nutrition impact symptoms (S-NIS) such as nausea may further contribute to weight loss by decreasing nutrient intake. In addition, treatable metabolic abnormalities such as hypogonadism, vitamin B12 deficiency, hypothyroidism, and hypoadrenalism could exacerbate anorexia and muscle wasting in patients with cancer cachexia. We determined the frequency and type of contributors to appetite and weight loss, and the effect of the cachexia clinic on clinical outcomes. METHODS Review of 151 consecutive patients referred to a cachexia clinic. All received dietary counseling and exercise recommendations. Assessments included weight, body mass index (BMI), S-NIS, resting energy expenditure by indirect calorimetry, serum thyroid stimulating hormone (TSH), cortisol, total testosterone, and vitamin B12. RESULTS Median weight loss in the 100 days before referral was 9% (4%-13%); median BMI at presentation was 20.8. Median number of S-NIS was 3 (2-4), most commonly treated by metoclopramide, laxatives, and antidepressants. Forty-one percent (24/59) of patients were hypermetabolic and 73% (52/71) of males hypogonadic, whereas hypoadrenalism (0/101, 0%), hypothyroidism (4/113, 4%), and low vitamin B12 (3/107, 3%) were uncommon. Poor appetite and weight loss before referral (r = 0.18, p = 0.036) were associated with increased S-NIS (r = 0.22, p = 0.008). Appetite improved (p < 0.001) and 31/92 (34%) of patients returning for a second visit gained weight. CONCLUSIONS Patients had a high frequency of multiple S-NIS, hypogonadism, and hypermetabolism. A combination of simple pharmacological and nonpharmacological interventions improved appetite significantly, and increased weight in one third of patients who were able to return for follow-up. Cachexia clinics are feasible and effective for many patients with advanced cancer.

Associations among hypogonadism, C-reactive protein, symptom burden, and survival in male cancer patients with cachexia: a preliminary report.

CONTEXT Cachexia is characterized by muscle wasting, anorexia, and elevated inflammatory markers. In patients without cancer, hypogonadism is associated with lower lean body mass, increased symptom burden, and decreased survival. Hypogonadism in cancer cachexia could exacerbate symptoms, facilitate a proinflammatory state, and decrease survival. OBJECTIVES To explore the relationships among these factors, a retrospective study of male cancer patients was conducted. METHODS The charts of 98 consecutive male patients referred to a cachexia clinic at a comprehensive cancer center were reviewed. All patients reported weight loss of >5% within the preceding six months; the median age was 60 years. Fifty-seven (58%) had serum C-reactive protein (CRP), and 68 (69%) had total testosterone evaluated. Symptoms were evaluated by the Edmonton Symptom Assessment Scale. RESULTS Median CRP was 20mg/L, and median testosterone level was 185 ng/dL (6.42 nmol/L) (normal > or = 240 ng/dL or 8.36 nmol/L). There was an inverse correlation between testosterone and CRP levels (P<0.01). Lower testosterone was associated with increased dyspnea and insomnia (P<0.05). Poor appetite and insomnia (P<0.05) correlated with elevated CRP. Survival of patients with testosterone levels < or = 185 ng/dL (6.42 nmol/L) was decreased compared with that of those with levels >185 ng/dL (13 vs. 62 weeks, P=0.004). Patients with CRP levels >10mg/L had decreased survival compared with those with levels < or = 10mg/L (15 vs. 46 weeks, P=0.01). The combination of hypogonadism and elevated CRP was associated with poorer prognosis. Elevated CRP levels were associated with increased symptom burden and decreased survival. Low testosterone was associated with decreased survival and correlated inversely with CRP levels, dyspnea, and insomnia. CONCLUSION Our preliminary results suggest that testosterone and CRP may be additive or synergistic as markers for survival in male patients and could be useful in future prognostic models.

Achievement of personalized pain goal in cancer patients referred to a supportive care clinic at a comprehensive cancer center

Cancer pain initiatives recommend using the personalized pain goal to tailor pain management. This study was conducted to examine the feasibility and stability of personalized pain goal, and how it compares to the clinical pain response criteria.

Is there a role for hydration at the end of life

Purpose of reviewTo review current evidence on issues central to the hydration debate. Recent findingsWorldwide, there are wide variations in hydration practice in terminally ill patients, reflecting divergent beliefs of medical providers, and the paucity in scientific evidence. This issue is particularly distressful to patients/families and nurses, yet their involvement in clinical decision-making remains insufficient. A short preliminary randomized controlled intervention trial (in advanced cancer patients) adds to the mounting evidence in support of hydration in improving neuro-cognitive symptoms associated with fluid deficits. On the other hand, majority of trials conducted in patients at the very end of life (survival days or weeks), while confirming high symptom burden, suggest no relationship to fluid status, or no significant benefit with hydration intervention. In Japan, the development of national clinical guidelines for hydration therapy in terminally ill cancer patients is a significant step forward, and brings attention to this important issue. SummaryAreas of future research should include patients at various stages of the illness trajectory and involve noncancer illnesses. Appropriately powered, randomized, double-blind studies of hydration are awaited. Till then, the recommendation is to individualize hydration decisions and include participation of patient/families and other disciplines.

Is there a role for parenteral nutrition or hydration at the end of life

Purpose of reviewThis review aims to update healthcare providers on the role of parenteral nutrition/hydration in terminal patients and highlight recent research. Recent findingsCachexia is felt to be refractory to treatment at the last stages of life. The majority of terminally ill patients will derive no benefit from parenteral nutrition with some exceptions including patients with a good functional status and a nonfunctional gastrointestinal tract or a slow growing tumor.Dehydration can potentially be reversible in patients at the end of life. However, recent research examining parenteral hydration reveals no clear clinical benefits on symptom burden or survival for terminally ill cancer patients with the exception of possibly reversing the complication of delirium. SummaryHydration and nutrition are essential for the maintenance of life. In patients at the end of life, artificial hydration and nutrition pose clinical, ethical, and logistical dilemmas. No strong evidence exists supporting the use of parenteral hydration/nutrition for the majority of terminally ill patients; however, a subset of patients may derive some benefit. Uncertainty about determining prognosis, psychosocial factors, and perceptions of perceived benefits results in artificial nutrition/hydration being initiated in terminally ill patients. Discontinuation of artificial support can result in distress for patients, family members, and healthcare providers.

Association Between Serum Cortisol and Testosterone Levels, Opioid Therapy, and Symptom Distress in Patients with Advanced Cancer

CONTEXT Patients with advanced cancer often experience symptoms such as pain, anorexia, and fatigue. Opioid therapy for the management of cancer pain may result in neurohormonal dysfunction that may contribute to a patients symptom burden. OBJECTIVES To examine the association between serum cortisol and testosterone levels, opioid therapy, and symptom distress in patients with cancer. METHODS A retrospective chart review was performed on 77 consecutive patients with advanced cancer referred for symptoms of fatigue or cachexia. We collected information regarding cortisol levels (am or random), testosterone levels (men only), morphine equivalent daily dose (MEDD), and symptom severity measured by the Edmonton Symptom Assessment Scale. Nonparametric correlation analysis was performed. RESULTS The median age was 63 years (range 24-79), and 62% were men (n=48). Most patients had gastrointestinal (n=33, 43%) or thoracic (n=21, 27%) malignancies and were Caucasian (n=46, 60%). The median random cortisol level was 19.1 μg/dL (Q1-Q3, 13.4-23.8 [normal, 4.3-22.4]), which correlated with MEDD (Spearman coefficient, 0.25, P=0.032) and symptoms including pain (0.50, P<0.001), fatigue (0.29, P=0.012), nausea (0.34, P=0.003), depression (0.24, P=0.032), and anxiety (0.25, P=0.031). Pain and nausea remained significant after Bonferroni correction. Median morning cortisol level (n=28) was 20.6 μg/dL (Q1-Q3, 16.6-25.4) and significantly correlated with pain (0.55, P=0.003) after Bonferroni correction. Patients with a MEDD <30 mg/day had a mean random cortisol level of 16.6 μg/dL, whereas patients with a MEDD ≥ 30 mg/day had a mean random cortisol level of 20.6 μg/dL (P=0.01). In 44 male patients with cancer, MEDD was inversely correlated with the total testosterone level (-0.52, P=0.001). CONCLUSION In patients with advanced cancer, elevated random cortisol levels were associated with pain and opioid use, although abnormally low levels of cortisol were found to be infrequent. Patients on higher opioid therapy (MEDD >30) had increased cortisol levels, and male patients had lower testosterone levels. Our study suggests that opioid therapy in patients with advanced cancer may inhibit gonadal function while sparing the adrenal axis. Future studies are needed.