Compare the effect of dexamethasone and placebo on cancer-related fatigue (CRF) and quality of life.

Dexamethasone 4 mg or placebo orally twice a day for 14 days.

• N = 84
• AVERAGE AGE: 60 years
• MALES: 47%, FEMALES: 53%  
• KEY DISEASE CHARACTERISTICS: Advanced multiple site-specific cancers: breast, lung, colon, prostate, other
• OTHER KEY SAMPLE CHARACTERISTICS: Three or more concurrent signs/symptoms in past 24 hours with a 4 or greater score for severity on the symptom scale

• SITE: Multi-site  
• SETTING TYPE: Outpatient    
• LOCATION: MD Anderson Cancer Center or Lyndon B. Johnson General Hospital

• PHASE OF CARE: Transition phase after active treatment
• APPLICATIONS: Elder care, palliative care 

• Randomized, double-blinded, placebo-controlled trial

• Edmonton Symptom Assessment Scale (ESAS)
• Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F)
• Functional Assessment of Anorexia/Cachexia Therapy (FAACT)
• Hospital Anxiety and Depression (HADS) questionnaire
• NCI Common Toxicity Criteria (v.3.0)

Dexamethasone and placebo groups had no differences in patient characteristics at baseline with the exception of more females in the dexamethasone group. Mean improvement scores of the FACIT-F subscale scores and ESAS physical distress scores were significantly better in the dexamethasone than the placebo group at days 8 (p = .005) and 15 (p = .008). ESAS pain was significantly better in the dexamethasone group on day 8. FAACT subscale scores were significantly better in the dexamethasone group on day 15. Fatigue did decline in both study groups. All other variables showed no significant differences in scores or frequency of adverse events.

Dexamethasone is more effective than placebo in improving CRF and quality of life in patients with advanced cancer.

• Small sample (< 100)
• Key sample group differences that could influence results
• Subject withdrawals were 10% or greater
• Other limitations/explanation: Adherence to schedule and actual taking of dexamethasone was not reported. It was unclear why patients with gastrointestinal or head and neck cancers were grouped in reporting sample characteristics. Limited justification of dose or schedule choice for administration of dexamethasone. The dropout rate was 34/120 subjects, as noted in the manuscript, although a sample size listed in a table was 132 subjects.

A need exists for larger, long-term studies to determine safety and efficacy in patients with cancer (palliative care and active treatment). A significant number of patients with advanced cancer present with multiple signs and symptoms that may or may not benefit from dexamethasone therapy. Clinicians should be aware of barriers to adherence with dexamethasone.

To determine the effects of thalidomide on anorexia-cachexia and related symptoms

Patients were randomized to receive either 100 mg of thalidomide or placebo orally for 14 days. Pre- and post-study measurements were done.

• A total of 21 patients completed the study.
• Median patient age was 60 years, with a range of 24–81 years.
• The sample was 59% male and 41% female.
• Patients had multiple tumor types.
• All patients had at least 5% weight loss in the past six months. All had to have anorexia and fatigue and at least one of the following symptoms within the preceding 24 hours: anxiety, depression, or sleep disturbance.
• The sample was mostly Caucasian; 15% was African American and 9% was Hispanic.

The study was conducted at a single site in an outpatient setting in Anderson, TX.

The study has clinical applicability for late effects and survivorship.

A randomized controlled trial design was used.

• Edmonton Symptom Assessment Scale
• Functional Assessment of Anorexia/Cachexia Therapy
• Hospital Anxiety and Depression Scale
• Pittsburgh Sleep Quality Index
• Bioelectrical impedance
• Cytokine levels

There was no significant change in appetite with thalidomide. Those receiving placebo had improvement in appetite at day 15 (p = 0.01). Body composition measures showed significant decline in body fat percent, fat mass, and fat-free mass by day 15 (p < 0.05), which reversed by day 29.

The study did not demonstrate any benefit of thalidomide for anorexia or related symptoms.

• The study had a small sample size, with less than 30 participants.
• Findings are not generalizable.
• Protocol fidelity was questionable. 
• Participant withdrawals were 10% or greater.
• The authors noted an approximate 30% drop-out rate and poor compliance of study participants.
• Sample inclusion criteria were very restrictive.

This study does not provide any conclusive findings due to the small sample size and other study limitations cited.

To determine the therapeutic safety and efficacy of phenylbutyrate (an antitumor histone deacetylase inhibitor and chemical chaperone) 5% mouthwash for treating oral mucositis caused by cancer therapy.  

One group received standard oral care plus 5 ml of phenylbutyrate 5% mouthwash (swish and spit) applied four times daily; the other group received standard oral care plus 5 ml of placebo that contained the same base of mouthwash but no phenylbutyrate.

The study was comprised of 31 patients (14 in the phenylbutyrate group and 17 in the placebo arm), age 20 years or older.

MALES (%) 11 treatment and 17 placebo, FEMALES (%) 6 treatment and 2 placebo

KEY DISEASE CHARACTERISTICS: Diagnosed with squamous HNC

OTHER KEY SAMPLE CHARACERISTICS: Diagnosed with squamous HNC

SITE: Multi-site

SETTING TYPE: Both inpatient and outpatient

LOCATION: Two medical centers in Taiwan

PHASE OF CARE: Active treatment

APPLICATIONS: Elderly care, end of life, and palliative care
 

RCT

• WHO mucositis score    
• Oral Mucositis Assessment Scale ulceration score
• Duration of OM
   

Study showed that at cumulative doses below 5,000 cGy, the WHO mucositis score and the mean OMAS ulceration scores were relatively low between both groups.  However, at cumulative doses above 5,000 cGy, the severity of the mucositis and ulceration increased in the placebo group and decreased in the phenylbutyrate group. From 5,500 to 7,500 cGy, the phenylbutyrate group showed a statistically significant decrease in the severity of mucositis (WHO p = 0.0262, OMAS ulceration score p = 0.049). At a cumulative RT dose of 6,000-7,000, the intensity of ulceration was significantly lower in patients that received phenylbutyrate. The median duration of symptomatic mucositis was 16 days in the control group and 50 days in the placebo group. Endpoints included safety and efficacy.

Phenylbutyrate benefited patients by reducing the risk of severe mucositis by 24% and decreasing extensive ulceration by 61%; this was accomplished by shortening the duration of severe mucositis and promoting wound healing during RT and CCRT. Authors suggest that phenylbutyrate might expedite recovery of OM post RT, and that patients treated with this might also retain the ability to eat more often.

• Small sample <100
• Small pilot trial not evaluating for prevention but for treatment.

By decreasing the severity and duration of OM, it can increase the patient’s ability to eat and possibly reduce episodes of N/V. A larger, Phase II trial would be indicated to illustrate benefit. The sample was just over 30.

To determine whether gabapentin is more effective than placebo in regard to reducing pain, sleep interference, functional limitation, and the frequency of adverse events in patients with chronic neuropathic pain; to assess whether patients find gabapentin tolerable

The trial was offered to two groups of patients who had shown a clinical response to gabapentin: Three cycles of gabapentin and placebo treatment pairs were assigned in random order, with each treatment lasting two weeks. Dose was titrated to a maximum of 1,800 mg/day, depending on response and adverse effects. Rate of titration was 300 mg twice daily to start; dose increased by 300 mg/day. Breakthrough medications were, most commonly, opioids.

• Of the 112 enrolled patients, 39 dropped out due to nonresponses.
• Of all patients, 59% were women and 41% were men.
• Mean patient age was 57.6 years.
• The sample included these diagnoses: phantom limb pain, poststroke pain, post-therapeutic neuralgia, diabetic neuropathy, and complex regional pain syndrome.

The study was conducted at two hospitals in Australia.

Randomized, double-blind placebo-controlled crossover trial

• Visual analog scale (VAS), to measure pain and sleep interference
• Patient-Specific Function scale, to measure function
• VAS, to rate the degree that pain limited activities of daily living
• A checklist that listed symptoms that could be adverse events
• Global assessment of medication preference

Only 29% of participants showed a positive response to gabapentin. The ceiling dose of 1,800 mg, compared to 3,600 mg in other studies, may have reduced response rates. The participant withdrawal rate of 35% was high but fairly typical of n-of-1 trials.

Approximately 33% of patients responded to gabapentin, indicating that the drug may be fairly effective.

• No patients with cancer pain were included in the study.
• A fairly low ceiling dose may have limited the effectiveness of the drug.

The study findings were in line with other research that has shown gabapentin to be useful for patients with neuropathic pain. Approximately 33% of participants found gabapentin useful. However, applicability of findings to patients with cancer is unclear.

To evaluate the effect of the ginger plant on chemotherapy-induced vomiting

The intervention persisted for six days starting three days before the chemotherapy session. During this period, all participants took four 250 mg capsules (Zintoma) at six-hour intervals (1 g per day) complemented by the routine antiemetic regimen, including Kytril, or granisetron hydrochloride tablets, (1 mg per day) and dexamethasone ampoules (8 mg per day). A self-made, two-part, self-reporting instrument was used to measure the number of vomiting cases in both the groups. Vomiting times were recorded in the instruments each night just before sleep. 

• N = 80
• AVERAGE AGE = (placebo group) 45.1 +/– 10 years; (intervention group) 41.8 +/– 8.4 years        
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer

• SITE: Single site  
• SETTING TYPE: Inpatient  
• LOCATION: Tehran, Iran

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Palliative care

Randomized, double-blind, placebo-controlled clinical trial

A self-made, two-part, self-reporting instrument was used to measure the number of vomiting cases in both the groups. This instrument was a reliable standard table that has been used in various studies.

The results of this randomized, controlled trial showed that ginger alleviated nausea and vomiting in patients in the ginger arm compared to the placebo group. Ginger could be a promising antiemetic herbal remedy; however, its positive effects could be dose-related or specific agent-related. Therefore, we need further evidence, including multiagent chemotherapy with different types of cancers.

• The paper stated that participants received single-day chemotherapy. Although the prescribed antiemetics (e.g., Kytril,  Zofran, and dexamethasone) were clearly identified, this paper lacked information regarding the names of the chemotherapy agents. According to Table 1, the researchers considered chemotherapy agents to be low to moderately emetogenic, and refer the reader to check the American Society of Clinical Oncology's guidelines.
• Small sample (< 100)
• Key sample group differences that could influence results
• Other limitations/explanation: This study was only done on women with breast cancer undergoing single-day courses of chemotherapy. Results were only connected with and applicable for patients with breast cancer and, consequently, cannot be generalized to other types of cancers.

The nursing implication was confined to teaching patients and their families about the ginger capsules.

To examine the feasibility of a home-based aerobic exercise intervention on reducing fatigue in children with acute lymphoblastic leukemia (ALL).

Institutional review board approval, parental consent and child assent, verbal and written explanations, and baseline assessments were completed. Maximal exercise tests were completed for all, and those in the intervention group were provided with a video and instructions on achieving target heart rate. Parents and patients were instructed on exercise guidelines, safety and health condition assessment, and monitoring. Heart rate monitors were worn and documented.  

The home-based aerobic exercise intervention consisted of following the steps in an exercise video three days a week, for 30 minutes each session, for six weeks. The content of the intervention included three sections:  a warm-up for five minutes, aerobic exercise for 25 minutes, and a cool-down for five minutes. The warm-up and cool-down were aimed to increase 10% to 30% of the heart rate reserve. This was recommended by the American College of Sports Physicians. The aerobic section was designed to increase the heart rate reserve to 40% to 60%. The exercise prescription was individualized after baseline assessment, and the duration ranged from 10 to 30 minutes, gradually increasing to 30 minutes by the third week and after. Patients were instructed to complete the exercise three times per week for six weeks.

• Twenty-two children were included in the study (12 in the intervention group [six boys and six girls; average age = 11.01 years] and 10 in the control group [six boys and four girls; average age = 12.48 years]).  
• They were matched by age and sex.  
• All patients received maintenance chemotherapy for 20 weeks, and they were recruited after completing the dexamethasone.  
• Ten patients (five boys and five girls) in the intervention group adhered to the exercise prescription.
• In the control group, five children (three boys and two girls) reported any exercise with their logs, and they were used for per-protocol (PP) analysis.  
• Of the patients, 54.% were female and 45.5% were male.
• Patients had ALL.
• All patients were receiving maintenance chemotherapy regimens of standard or high-dose chemotherapy.

• Single site
• Home
• Taiwan

• Patients were undergoing the active treatment phase of care.
• The study has clinical applicability for pediatrics and late effects and survivorship.

This was a quasiexperimental control study with multivariate analysis on self-reported levels of fatigue at posttest and one-month follow-up.

• Pediatric Quality of Life Inventory (PedsQL) Multidimensional Fatigue Scale 
• Physical activity log
• Children’s OMNI-Walk/Run Scale
• Stage of change-exercise behavior
• Maximal exercise test for assessing cardiorespiratory fitness
• Only subjective data were reported.
• Hemoglobin was measured to assess for confounding variables, but it was not related to fatigue change patterns.

For the PP analysis, children who received the exercise intervention reported lower general fatigue subscale scores than those in the control group at one-month follow-up (p = 0.03). There were no significant differences between groups at any other study timepoint. For intent-to-treat (ITT) analysis, there was no intervention and time effect for any of the three fatigue subscales at posttest or one-month follow-up. Descriptive statistics were collected, and the intervention effects of the home exercise and data were measured using the mixed-effects model (mixed procedure in SAS). This included fixed-effects for time and group. ITT (for all patients) and PP (for those who adhered to exercise) analyses were used. The mean adherence rate for the six-week intervention was 76% in the ITT analysis and 90% in the PP analysis.

This exercise program was feasible. Children who received the home-based aerobic exercise intervention reported lower “general fatigue” than those in control group at one-month follow-up. There was structured parental involvement, which might have played a role in adherence. Motivating children with cancer to exercise will require additional study.

• The study had a small sample size, with less than 30 participants. 
• The study had potential risks of bias due to no random group assignment and no blinding.

A home-based aerobic intervention program might reduce fatigue in children with ALL who are undergoing maintenance chemotherapy. This study demonstrated a high level of adherence, which the authors attributed to parental involvement. Larger, well-designed clinical trials should be performed to further examine the role of exercise in managing fatigue in these patients, as well as the importance and degree of parental involvement needed for success.

To evaluate a method of Chan-Chuang qigong to manage fatigue and sleep disturbance in individuals undergoing chemotherapy for non-Hodgkin lymphoma

Participants randomly assigned to the intervention group received qigong guidance booklets that introduced qigong and provided illustrations of qigong procedures and precautions, as well as daily monitoring guidelines. Study participants were individually trained by qigong practitioners who followed a set study protocol. Initial training of study participants was completed during their two-day hospital stay for first cycle of treatment. The study nurse observed the participant’s qigong practice until his or her form/movement was satisfactory. After discharging patients, the study nurse called them weekly to confirm they were practicing qigong at home. The study recommended two to three (but no more than five) sessions a day of qigoing practice equally spaced in time. This study followed participants for three weeks (21 days).

• N = 102   
• AGE = 59.8 years (16.5)
• MALES: 56%, FEMALES: 44%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: non-Hodgkin lymphoma

• SITE: Single site   
• SETTING TYPE: Multiple settings; inpatient initially, then outpatient
• LOCATION: Northern Taiwan

PHASE OF CARE: Active antitumor treatment

This was a randomized, controlled trial with a two-group design (intervention and control). No blinding was used in this study.

• Fatigue intensity (two questions on an 11-point scale)
• Verran and Snyder-Halpern Sleep Scale

Participants assigned to the intervention (qigong) group reported significantly lower levels of fatigue and improved sleep quality compared with the control group (p < 0.001). Participants reported a near 100% adherence to intervention and completed on average two sessions for a mean time of 47 minutes total.  No adverse effects were reported from this intervention.

• Risk of bias (no blinding)
• Key sample group differences that could influence results

No side effects were reported by the intervention group. The results suggested that qigong may mitigate fatigue and sleep disturbance. However, the high adherence rate may be related to culture belief.

To analyze the differences between ondansetron and palonosetron in healthcare resource use (i.e., inpatient/outpatient encounters) among patients receiving intraperitoneal (IP) cisplatin

This study reported on a review of an electronic medical record system. Key variables were patient characteristics, chemotherapy regimen, diagnosis, medications, type of 5-HT₃ receptor antagonist (RA), other healthcare resource use, and reasons for use.

• The study reported on 48 patients; however, analysis was based on each IP administration.
• Mean age was 59 years.
• All patients were female.
• The most common cancer diagnosis was ovarian, followed by fallopian tube.
• All patients were receiving IP cisplatin as part of the GOG-172 regimen (six cycles: paclitaxel on day 1 as 24-hour IV infusion (135 mg/m² BSA), IP cisplatin on day 2 (100 mg/m² BSA), hydration on day 3 and discharge, and IP cisplatin (60 mg/m² BSA) on day 8 in the outpatient clinic). 
• Antiemetic coverage was 5-HT₃ RA plus aprepitant and dexamethasone on days 2–3, and aprepitant plus dexamethasone on day 4.
• For breakthrough CINV, prochlorperazine, metoclopramide, diphenhydramide, and lorazepam were prescribed. Patients received dexamethsone on day 1 for fluid retention purposes (not for the control of CINV).

This was a single-site, inpatient and outpatient study conducted in Massachusetts.

• Patients were undergoing the active treatment phase of care.
• The study has clinical applicability for late effects and survivorship.

This was an observational study (electronic chart review).

The following were recorded.

• CINV-related hospital readmission occurrence    
• Emergency department visits
• Outpatient encounters (clinic visits, telephone calls) occurring within 7 days after cisplatin administration
• CINV-related resource use: events associated with dehydration, hypovolemia, nausea/vomiting, hypokalemia, constipation, shortness of breath, syncope/collapse
   

More CINV-related hospitalizations were found with ondansetron versus palonosetron (5.1% vs. 0%, p = 0.09) with no significant difference in other CINV-related encounters. Palonosetron was always administered as single-day therapy; ondansetron was administered as one-day (27%) or multiday (73%) therapy. No significant differences were found in hospital readministrations, emergency department visits, outpatient visits, or switches to alternate 5-HT₃ RAs between palonosetron and ondansetron. When CINV-related resource use was compared, a trend to more hospitalization was noted in the ondansetron arm, although it was not significant (2 out of 39 in the ondansetron arm versus 0 out of 89 in the palonosetron arm).

Palonosetron was associated with a trend to a lower risk of CINV-related hospital readmission than ondansetron in patients receiving IP cisplatin for gynecological cancers; however, the trend was not statistically significant. The duration of ondansetron therapy might be suboptimal with 27% of patients receiving only one day of therapy during hospital stay.

• No appropriate control group was included.
• Three different data collection periods were used.
• Suboptimal antiemetic intervention was used on day 1 (only dexamethasone for fluid retention purpose).
• Medications taken on an as-need basis and after discharge were not tracked.
• Patients who used healthcare facilities not affiliated with the study institution were not captured.
• Healthcare resource use after 7 days of IP chemo was not assessed. 
• The sample size was small (the study should have had 79 cases in each 5-HT₃ RA arm; however, only 48 patients were included), and the unit of analysis was not each individual patient, but each IP chemotherapy administration.
• Risk factors for CINV were not considered.
• The methodological quality of this study is low.

Because of the design and limitations, this study does not help in building evidence for the conclusion that palonosetron has a lower risk of CINV-related readmission compared to ondansetron.

To report the effects of treatment with zoledronic acid on pain and quality of life outcomes

Patients treated with zoledronic acid monthly for 24 months were observed for 22 months. Quality of life and pain were measured every two months.

• N = 366
• MEAN AGE = 53.7 years (SD = 11 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All patients had breast cancer and radiologic evidence of bone metastases, and 46% had two to five bone lesions. 

• SITE: Multi-site  
• SETTING TYPE: Multiple settings  
• LOCATION: Taiwan

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Palliative care 

Phase 4, single-arm, open-label, observational study

• European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) BM22 for quality of life
• 100 mm Visual Analog Scale (VAS) for pain severity

VAS scores declined significantly on a monthly basis for the first 22 months (p < 0.05) then returned to baseline levels. Pain-related subscales of the QLQ also declined in the same pattern. There was no significant change in psychosocial aspects of the functional interference scale in the QLQ.

Over a 22-month period, monthly treatment with zoledronic acid reduced pain in women with bone metastases from breast cancer.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Unintended interventions or applicable interventions not described that would influence results
• Other limitations/explanation: No information was provided regarding whether there were any changes in analgesics.

Zoledronic acid is a type of bisphosphonate. Bisphosphonates are effective in reducing pain and skeletal events from bone metastases in patients with cancer. The duration of their effects was shown to be about 22 months in this study.

To determine the feasibility and preliminary efficacy of auricular acupressure as an adjunct for pain treatment

The auricular points selected were individualized and ranged between five and nine points. Vaccaria seeds were taped in place to stimulate the acupoints. An acupoint locator was used to identify points for use. After the seeds were taped to the ear areas, participants were told to press each of the taped acupoints at least three times per day for three minutes, even if they did not have symptoms. Tape remained in place for seven days. Patients were called each day for the collection of data regarding pain and medication use. Each patient received written material about the acupressure technique.

• N = 50
• MEAN AGE = 65.5 years (range = 43–89 years)
• MALES: 46%, FEMALES: 54%
• KEY DISEASE CHARACTERISTICS: All had pain intensities of 3 or more on an 11-point scale; multiple tumor types
• OTHER KEY SAMPLE CHARACTERISTICS: 92% Caucasian; 8% African American; 94% had at least secondary education; 72% were in active treatment

• SITE: Single site  
• SETTING TYPE: Home  
• LOCATION: Taiwan

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Palliative care 

Quasi-experimental

• Brief Pain Inventory (BPI)
• Medication Quanitification Scale (MQS) v3.0
• Adaptation of the Perceived Treatment Efficacy (PTE) assessment in rheumatoid arthritis

Pain severity, worst pain, average pain, and pain interference all declined over time (p < 0.001). Perceived efficacy was not statistically different over time. Average pain was lowest on day 3 and then began to increase. Overall, there was a 58.4% reduction in average pain. In total, 63% of participants took less pain medication than before the treatment, and only 8% were not satisfied with the treatment. Finally, 91% of recruited patients completed the study.

Auricular acupressure as an adjunctive pain treatment may be effective for patients with cancer-related pain. The self-management of auricular acupressure was feasible.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias (no appropriate attentional control condition)  
• Other limitations/explanation: No information was provided about types of pain or analgesics used. Baseline pain levels were relatively low.

Auricular acupressure may be beneficial as an adjunctive analgesic treatment for patients with cancer-related pain. Patient self-treatment at home for seven days was feasible and well-received. Additional well-designed research of this intervention is warranted, and more research reporting the types of analgesics employed is needed.