Sriram Yennurajalingam

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.

Impact of a Palliative Care Consultation Team on Cancer-Related Symptoms in Advanced Cancer Patients Referred to an Outpatient Supportive Care Clinic

CONTEXT Patients with advanced cancer may develop severe physical and psychosocial symptoms. There are limited data on the impact of an outpatient palliative consultation (PC) team on cancer-related symptoms. OBJECTIVES To study the impact of the PC on symptoms in patients with advanced cancer receiving outpatient palliative care. METHODS Four hundred six consecutive patients referred to a supportive care outpatient center (OPC) from January 2006 to June 2007 with complete Edmonton Symptom Assessment Scale (0-10 scale) at the initial and follow-up visits were reviewed. Patient characteristics, change of symptoms at follow-up visit, and response rate were analyzed. Using logistic regression models, the predictors of improvement of pain and fatigue were assessed. RESULTS Median age was 59 years; 53% were female. Median interval between visits was 15 days. Mean scores at baseline and follow-up visits were fatigue 6.8 and 5.3 (P<0.0001), pain 5.3 and 4.1 (P<0.0001), depression 3.2 and 2.5 (P<0.0001), anxiety 3.7 and 2.8 (P<0.0001), dyspnea 2.7 and 2.5 (P=0.05), sleep 5 and 4 (P<0.0001), and well-being 5.2 and 4.4 (P<0.0001). Dyspnea (odds ratio and P-value, 0.90, 0.03), nausea (0.92, 0.06), and depression (0.91, 0.04) were associated with improvement in fatigue; drowsiness (1.10, 0.04), and feeling of well-being (0.87, 0.02) were associated with improvement in pain. CONCLUSION The initial consult by PC achieved significant symptom improvement in patients receiving treatment in the OPC. Further prospective studies are needed.

Methylphenidate and/or a Nursing Telephone Intervention for Fatigue in Patients With Advanced Cancer: A Randomized, Placebo-Controlled, Phase II Trial

PURPOSE Cancer-related-fatigue (CRF) is common in advanced cancer. The primary objective of the study was to compare the effects of methylphenidate (MP) with those of placebo (PL) on CRF as measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) fatigue subscale. The effect of a combined intervention including MP plus a nursing telephone intervention (NTI) was also assessed. PATIENTS AND METHODS Patients with advanced cancer with a fatigue score of ≥ 4 out of 10 on the Edmonton Symptom Assessment Scale (ESAS) were randomly assigned to one of the following four groups: MP+NTI, PL+NTI, MP + control telephone intervention (CTI), and PL+CTI. Methylphenidate dose was 5 mg every 2 hours as needed up to 20 mg per day. The primary end point was the median difference in FACIT-F fatigue at day 15. Secondary outcomes included anxiety, depression, and sleep. RESULTS One hundred forty-one patients were evaluable. Median FACIT-F fatigue scores improved from baseline to day 15 in all groups: MP+NTI (median score, 4.5; P = .005), PL+NTI (median score, 8.0; P < .001), MP+CTI (median score, 7.0; P = .004), and PL+CTI (median score, 5.0; P = .03). However, there were no significant differences in the median improvement in FACIT-F fatigue between the MP and PL groups (5.5 v 6.0, respectively; P = .69) and among all four groups (P = .16). Fatigue (P < .001), nausea (P = .01), depression (P = .02), anxiety (P = .01), drowsiness (P < .001), appetite (P = .009), sleep (P < .001), and feeling of well-being (P < .001), as measured by the ESAS, significantly improved in patients who received NTI. Grade ≥ 3 adverse events did not differ between MP and PL (40 of 93 patients v 29 of 97 patients, respectively; P = .06). CONCLUSION MP and NTI alone or combined were not superior to placebo in improving CRF.

Discharge Outcomes and Survival of Patients with Advanced Cancer Admitted to an Acute Palliative Care Unit at a Comprehensive Cancer Center

BACKGROUND Acute palliative care units (APCUs) are new programs aimed at integrating palliative and oncology care. Few outcome studies from APCUs are available. OBJECTIVES We examined the frequency, survival, and predictors associated with home discharge and death in our APCU. METHODS All patients discharged from the APCU between September 1, 2003 and August 31, 2008 were included. Demographics, cancer diagnosis, discharge outcomes, and overall survival from discharge were retrieved retrospectively. RESULTS The 2568 patients admitted to APCU had the following characteristics: median age, 59 years (range, 18-101); male, 51%; median hospital stay, 11 days; median APCU stay, 7 days; and median survival 21 days (95% confidence interval [CI] 19-23 days). Five hundred ninety-two (20%), 89 (3%), and 1259 (43%) patients were discharged to home, health care facilities, and hospice, respectively, with a median survival of 60, 29, and 14 days, respectively (p < 0.001). Nine hundred fifty-eight (33%) patients died during admission (median stay, 11 days). Compared to hospice transfers, home discharge (hazard ratio = 0.35, 95% CI 0.30-0.41, p < 0.001) was associated with longer survival in multivariate analysis, with a 6-month survival of 22%. Multivariate logistic regression revealed that male gender, specific cancer primaries, and admissions from oncology units were associated with death in the APCU, while younger age and direct admissions to the APCU were associated with home discharge. CONCLUSIONS Our APCU serves patients with advanced cancer with diverse clinical characteristics and survival, and discharged home a significant proportion with survival greater than 6 months. RESULTS from this simultaneous care program suggest a pattern of care different from that of traditional hospice and palliative care services.

Association Between Self-Reported Sleep Disturbance and Other Symptoms in Patients with Advanced Cancer

CONTEXT Sleep disturbance (SD) is a significant source of distress for patients with cancer. Studies of patients with advanced cancer receiving palliative care to identify symptoms associated with the severity of SD are limited. OBJECTIVES In this study, we sought to identify the symptoms measured by the Edmonton Symptom Assessment Scale (ESAS) that are associated with SD, as measured by the Pittsburgh Sleep Quality Index (PSQI). Secondary aims of the study were to determine the association between occurrences of SD with occurrences of other symptoms and screening performance of the ESAS-Sleep item against the PSQI. METHODS We reviewed the completed ESAS and PSQI assessments of 101 patients with advanced cancer who were receiving palliative care and had been admitted to prospective clinical trials previously initiated by us. Patients with a PSQI score of ≥ 5 were considered to have an SD. The frequency and severity of the ESAS symptoms items, their correlation with each other, the PSQI score, and the screening performance of the ESAS-Sleep item were calculated. RESULTS The median age of patients was 60 years. Most were white non-Hispanic (73%), had lung or breast cancer (41%), and were diagnosed with SD (85%). The PSQI score was correlated with the ESAS items of pain (r=0.27, P=0.006), dyspnea (r=0.25, P<0.001), well-being (r=0.35, P<0.0001), and sleep (r=0.44, P<0.0001). Compared with patients without SD, those with SD were more likely to report pain (P=0.0132), depression (P=0.019), anxiety (P=0.01), and a poorer sense of well-being (P=0.035). An ESAS-Sleep item cutoff score of ≥ 3 (of 10) resulted in a sensitivity of 74% and a specificity of 73%. CONCLUSION SD is associated with increased frequency of pain, depression, anxiety, and a worse sense of well-being. These four symptoms should be assessed in all patients with advanced cancer with a complaint of SD. The ideal cutoff point of the ESAS-Sleep item for screening for SD is a score of ≥ 3. More research is needed to better characterize this frequent and distressing syndrome.

Palliative Care in Advanced Cancer Patients: How and When?

Cancer patients develop severe physical and psychological symptoms as a result of their disease and treatment. Their families commonly suffer great emotional distress as a result of caregiving. Early palliative care access can improve symptom control and quality of life and reduce the cost of care. Preliminary results show that early palliative care access can also extend survival. Unfortunately, only a minority of cancer centers in the U.S. have the two most important resources for palliative care delivery: outpatient palliative care centers and inpatient palliative care units. In this article, we use a case presentation to discuss the impact of early palliative care access in light of the currently available evidence, and we recommend ways to improve early access to palliative care through education and research.

Association between fatigue and other cancer-related symptoms in patients with advanced cancer

Goals of workAlthough fatigue is the chronic symptom most commonly experienced by patients with advanced cancer, little research has been done on the associations and correlates of fatigue in this population. The aim of this study was, therefore, to determine whether fatigue scores, as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), are associated with age, gender, type of cancer diagnosed, pain, and other cancer-related symptoms measured using the Edmonton Symptom Assessment Scale (ESAS).Materials and methodsWe retrospectively reviewed the FACIT-F (when a higher score denotes lower fatigue) and ESAS (when a lower fatigue score denotes lower fatigue intensity) scores of 268 patients with advanced cancer who had been previously enrolled in clinical trials of therapies for fatigue. To determine associations between variables, we performed univariate and multivariate analyses on the data.ResultsWe found no univariate association between fatigue score and gender, ethnicity (p = 0.31), or type of cancer diagnosed. Performance status was associated with fatigue (p < 0.0001). On multivariate analysis, we found, however, significant association between fatigue and pain (r = −0.20, p = 0.0012), nausea (r = −0.13, p = 0.04), anxiety (r = −0.27, p < 0.0001), fatigue and depression (r = −0.19, p = 0.0019), drowsiness (r = −0.24, p = 0.0002), dyspnea (r = −0.17, p = 0.007), anorexia (r = −0.29, p < 0.0001), insomnia (r = −0.25, p < 0.0001), and feelings of well-being (r = −0.37, p < 0.0001). Using backward stepwise logistic regression analysis, independent correlative factors associated with fatigue include well-being (p = .0003), drowsiness (0.006), anorexia (0.01), and anxiety (0.03). However, this model only explained 21% of the variation in the intensity of fatigue.ConclusionsAlthough we found that fatigue is significantly associated with the severity of psychological symptoms (anxiety and depression) and physical symptoms (pain, dyspnea, insomnia, anorexia, and drowsiness), additional research is required to confirm that these are indeed the main associations of fatigue and, by doing so, enable physicians to better characterize fatigue in patients receiving palliative care.

The impact of an outpatient palliative care consultation on symptom burden in advanced prostate cancer patients.

OBJECTIVES There are limited studies characterizing cancer-related symptoms in outpatient advanced prostate cancer patients. The aim of this retrospective study was to describe the impact of an outpatient palliative care (PC) consultation on symptoms in patients with advanced prostate cancer. METHODS We retrospectively reviewed the medical records of 55 consecutive patients with advanced prostate cancer seen in our institutions outpatient PC center. Information regarding demographics, disease status, Edmonton Symptom Assessment System (ESAS) scores, Eastern Cooperative Oncology Group (ECOG) Performance Status, laboratory data, and pharmacological interventions were analyzed. RESULTS The median age of the studys patients was 66 years old, with 73% Caucasian ethnicity. All patients had metastatic disease and 96% had received prior cytotoxic chemotherapy. The most frequently occurring symptoms upon presentation were pain, fatigue, and drowsiness (>50%). Pain and fatigue were also the most severe symptoms, each having median ESAS scores of 7 (on a 0-10 scale). We instituted a median of 3 pharmacological interventions per patient, with a median of 15 days to follow-up assessment. At follow-up, patients reported significant symptom improvements in pain, drowsiness, fatigue, depression, sleep, sense of well-being, and anxiety. CONCLUSIONS Based on our preliminary data, we conclude that patients with advanced prostate cancer referred to PC experience severe and clinically significant symptoms. An outpatient PCconsultation is associated with significant symptom improvement in this subset of a distressed population. Future prospective studies are warranted to further describe symptom burden and the role for outpatient PC for advanced prostate cancer patients.

Clinical Response to an Outpatient Palliative Care Consultation in Patients With Advanced Cancer and Cancer Pain

CONTEXT There is limited published data regarding the outcomes of palliative care consult on cancer pain treatment at the first follow-up visit. OBJECTIVES The primary aim of this study was to determine pain treatment response to an outpatient palliative care consultation at the first follow-up visit for patients with cancer pain. METHODS Data from consecutive patients (n=1612) who were referred to the outpatient Supportive Care Center at The University of Texas M. D. Anderson Cancer Center and completed the Edmonton Symptom Assessment System at their initial and subsequent visits from January 2003 to December 2010 were reviewed. All patients received interdisciplinary care led by palliative care specialists following an institutional protocol. Pain treatment response was defined as a ≥2 point or ≥30% reduction from baseline. Using logistic regression models, predictive factors associated with pain treatment response were assessed. RESULTS The mean (SD) baseline pain was 5.36 (2.9). Of the 1612 patients, 462 (29%) rated their pain as mild (numeric rating scale [NRS] score 0-3), 511 (32%) as moderate (NRS score 4-6), and 639 (39%) as severe (NRS score 7-10). Almost half (728 of 1612 [45%]) of the patients achieved pain treatment response. However, 228 of 728 (31%) responding patients still had pain ≥4 at the first follow-up visit in 15 days on average. Of the 462 patients with mild pain at baseline, 147 (32%) had worse pain at the first follow-up visit. Factors associated with clinical response were baseline pain intensity (odds ratio [OR] per point 1.4; P<0.01), fatigue (OR per point 1.01; P=0.014), and Edmonton Symptom Assessment System symptom burden (OR per point 1.01; P=0.039). CONCLUSION More than half of the patients with moderate/severe pain were nonresponders, and about one-third of the patients with mild pain had an increase in pain severity to moderate/severe levels at the first follow-up. More frequent follow-up visits, phone calls, and interdisciplinary clinics may improve pain control.

Early Referral to Supportive Care Specialists for Symptom Burden in Lung Cancer Patients: A Comparison of Non-Hispanic Whites, Hispanics, and Non-Hispanic Blacks

Effective management of symptoms in cancer patients requires early intervention. This study assessed whether the timing of referral to the Supportive Care Center (SCC) and symptom burden outcome varied by race or ethnicity in lung cancer patients who had been seen at a tertiary cancer center.