Susan Frisbee-Hume

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.

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.

Once daily, oral, outpatient quinolone monotherapy for low-risk cancer patients with fever and neutropenia : A pilot study of 40 patients based on validated risk-prediction rules

The objective of this study was to assess the feasibility of empiric, oral, outpatient quinolone monotherapy in 40 adult patients with fever and neutropenia who were at low risk for serious medical complications.

Frequency, Outcome, and Predictors of Success Within 6 Weeks of an Opioid Rotation Among Outpatients with Cancer Receiving Strong Opioids

BACKGROUND Opioid rotation is used to treat uncontrolled pain and/or opioid-related adverse effects. Our aim was to determine the frequency, indications, outcomes, and predictors of successful opioid rotation in outpatients with cancer. METHODS Medical records of consecutive outpatients with cancer who received strong opioids and returned for follow-up visit within ≤6 weeks to our supportive care center from January to December 2008 were reviewed. Data on patient characteristics, symptoms, opioid use, indications for opioid rotation, outcomes, and morphine equivalent daily dose were collected. Successful opioid rotation was defined as a two-point or 30% reduction in the symptom score or the resolution of opioid-induced neurotoxicity and continuation of the new opioid at follow-up. RESULTS Opioid rotation was performed in 120 of 385 patients (31%). The median patient age was 55 years. There were 6/120 patients with missing data. Of the 114 evaluable patients, 68 (60%) were men, 81 (71%) were white, 27 (24%) had gastrointestinal cancer, and 90 (80%) had advanced-stage disease. The median Eastern Cooperative Oncology Group score was 1 (interquartile range: 1-2) and the median time between opioid rotation and follow-up was 14 days (interquartile range: 7-21 days). The most common indications for opioid rotation were uncontrolled pain (95/114; 83%) and opioid-induced neurotoxicity (13/114; 12%). A total of 35 patients (31%) had partial opioid rotation. The median improvements in pain and symptom distress score were -2 (interquartile range: -4 to 0; p < .001) and -5 (interquartile range: -14 to 7; p = .004), respectively. The morphine equivalent daily dose did not change significantly after opioid rotation (p = .156). A total of 65% of patients (74/114) had successful opioid rotation. There were no clinically significant independent predictors for successful opioid rotation. CONCLUSION Opioid rotation was conducted in 31% of outpatients with cancer, with a 65% success rate. The most frequent reason for opioid rotation was uncontrolled pain. There were no independent predictors for successful opioid rotation.

Patterns of Storage, Use, and Disposal of Opioids Among Cancer Outpatients

PURPOSE Improper storage, use, and disposal of prescribed opioids can lead to diversion or accidental poisoning. Our objective was to determine the patterns of storage, utilization, and disposal of opioids among cancer outpatients. PATIENTS AND METHODS We surveyed 300 adult cancer outpatients receiving opioids in our supportive care center and collected information regarding opioid use, storage, and disposal, along with scores on the CAGE (cut down, annoyed, guilty, eye-opener) alcoholism screening questionnaire. Unsafe use was defined as sharing or losing opioids; unsafe storage was defined as storing opioids in plain sight. RESULTS The median age was 57 years. CAGE was positive in 58 of 300 patients (19%), and 26 (9%) had a history of illicit drug use. Fifty-six (19%) stored opioids in plain sight, 208 (69%) kept opioids hidden but unlocked, and only 28 (9%) locked their opioids. CAGE-positive patients (p = .007) and those with a history of illicit drug use (p = .0002) or smoking (p = .03) were more likely to lock their opioids. Seventy-eight (26%) reported unsafe use by sharing (9%) or losing (17%) their opioids. Patients who were never married or single (odds ratio: 2.92; 95% confidence interval: 1.48-5.77; p = .006), were CAGE positive (40% vs. 21%; p = .003), or had a history of illicit drug use (42% vs. 23%; p = .031) were more likely to use opioids unsafely. Overall, 223 of 300 patients (74%) were unaware of proper opioid disposal methods, and 138 (46%) had unused opioids at home. CONCLUSION A large proportion of cancer patients improperly and unsafely use, store, and dispose of opioids, highlighting the need for establishment of easily accessed patient education and drug take-back programs.

In vitro antimicrobial activity of moxifloxacin compared to other quinolones against recent clinical bacterial isolates from hospitalized and community-based cancer patients.

The in vitro spectrum of moxifloxacin (a C-8-methoxyquinolone) was compared to that of ciprofloxacin and levofloxacin against 924 recent clinical isolates from cancer patients. Moxifloxacin was more active than the comparator agents against Gram-positive pathogens, with potent activity against Aerococcus spp., Listeria monocytogenes, Micrococcus spp., Rhodococcus equi, and Stomatococcus mucilaginous, methicillin-susceptible Staphylococcus spp., all beta hemolytic streptococci, viridans streptococci and Streptococcus pneumoniae. It also had good to moderate activity against Bacillus spp., Corynebacterium spp., Enterococcus faecalis, and methicillin-resistant staphylococci. Although ciprofloxacin was the most active agent tested against the Enterobacteriaceae, moxifloxacin inhibited the majority of these isolates at < or =2.0 microg/ml. Moxifloxacin was the least active of the three agents tested against Pseudomonas aeruginosa, but had significant activity against other non-fermentative Gram-negative bacilli including Acinetobacter spp., Flavobacterium spp., Pseudomonas spp. other than P. aeruginosa, and Stenotrophomonas maltophilia. The overall broad spectrum of moxifloxacin, and its availability for both oral and parenteral administration, warrants its evaluation for the prevention and treatment of infections in cancer patients.

Vascular access by physician assistants: evaluation of an implantable peripheral port system in cancer patients.

PURPOSE To determine the ability of a physician assistant (PA) to insert, in an ambulatory setting, a peripheral subcutaneous implanted vascular-access device (VAD) and to evaluate the ability to transfer this training to a second PA. We also evaluated the performance and complications associated with this new device. PATIENTS AND METHODS The Peripheral Access System (PAS) Port catheter system (Sims-Deltec Inc, St Paul, MN) was inserted in patients who required long-term (> 3 months) vascular access for infusion therapy. RESULTS The first PA (PA-1) successfully inserted 57 of 62 devices (92%) after gaining experience with the technique in 10 patients (success rate, five of 10 [50%]; P = .003). The second PA (PA-2) was successful in eight of 10 initial attempts (80%) and 25 of 30 overall (83%). Complications were few and limited to phlebitis, thrombosis, and a low infection rate (0.2 per 1,000 catheter days). CONCLUSION PAs can be taught to insert a peripheral subcutaneous implanted VAD. This technique is transferable from one PA to another, and the device studied is appropriate for outpatient VAD programs.

Characteristics and Outcomes of Patients Admitted to the Acute Palliative Care Unit From the Emergency Center

CONTEXT Most patients admitted to acute palliative care units (APCUs) are transferred from inpatient oncology units. We hypothesized that patients admitted to APCUs from emergency centers (ECs) have symptom burdens and outcomes that differ from those of transferred inpatients. OBJECTIVES The purpose of this retrospective cohort study was to compare the symptom burdens and survival rate of patients admitted to an APCU from an EC with those of inpatients transferred to the APCU. METHODS Among the 2568 patients admitted to our APCU between September 1, 2003 and August 31, 2008, 312 (12%) were EC patients. We randomly selected 300 inpatients transferred to the APCU as controls (The outcome data were unavailable for two patients). We retrieved data on patient demographics, cancer diagnosis, Edmonton Symptom Assessment System scores, discharge outcomes, and overall survival from time of admission to the APCU. RESULTS The EC patients had higher rates of pain, fatigue, nausea, and insomnia and were less likely to be delirious. They were more than twice as likely to be discharged alive than transferred inpatients. Kaplan-Meier plot tests for product-limit survival estimate from admission to APCU for EC patients and inpatients were statistically significant (median survival 34 vs. 31 days, P<0.0001). In multivariate analysis, EC admission (odds ratio [OR]=1.8593, 95% confidence interval [CI] 1.1532-2.9961), dyspnea (OR=0.8533, 95% CI 0.7892-0.9211), well-being (OR=1.1192, 95% CI 1.0234-1.2257), and delirium (OR=0.3942, 95% CI 0.2443-0.6351) were independently associated with being discharged alive. CONCLUSION The EC patients have a higher acute symptom burden and are more likely to be discharged alive than transferred inpatients. The APCU was successful at managing symptoms and facilitating the discharge of both inpatients and EC patients to the community although the patients had severe symptoms on admission.

Antimicrobial activity of a novel des-fluoro (6) quinolone, garenoxacin (BMS-284756), compared to other quinolones, against clinical isolates from cancer patients

The in vitro spectrum of a novel des-fluoro (6) quinolone, garenoxacin (BMS-284756), was compared with that of ciprofloxacin, levofloxacin, and trovafloxacin against 736 clinical isolates from cancer patients. Garenoxacin was the most active agent overall against Gram-positive organisms, with potent activity against Aerococcus spp., Micrococcus spp., Rhodococcus equi, Stomatococcus mucilaginous, Bacillus spp., Enterococcus faecalis, Listeria monocytogenes, methicillin-susceptible Staphylococcus spp., and all beta-hemolytic and viridans streptococci. Although ciprofloxacin was the most active agent tested against the Enterobacteriaceae garenoxacin inhibited the majority of these isolates at <or=4.0 microg/ml, its proposed susceptibility break-point. All 4 agents had sub-optimal activity against Pseudomonas aeruginosa and variable activity against other non-fermenters, with Stenotrophomonas maltophila and Alcaligenes spp. being the most resistant isolates. The overall broad spectrum of garenoxacin warrants its evaluation for the prevention or treatment of infections in cancer patients.