To compare the effectiveness of oral cryotherapy (OC) to room temperature saline rinses in prevention of oral mucositis (OM) in patients with multiple myeloma (MM) and lymphoid neoplasias (NHL, HL) for autologous stem cell transplantation (ASCT)

An oral care protocol with sodium bicarbonate mouthwash from day 7 of ASCT until hospital discharge was implemented for all patients in the study. The intervention group received oral cryotherapy before infusion for 10 minutes, during infusion for 15 minutes, and after HDmel for 15 minutes. The control group received saline salt rinses at room temperature, but the schedule was not described in the study. Nurses assessed for oral mucositis on the day before ASCT and on days 3, 6, 9, and 12 after infusion. 

• N = 134  
• MEDIAN AGE = 55-56 years (range = 23–70 years)
• MALES: 64%, FEMALES: 35%
• KEY DISEASE CHARACTERISTICS: MM = 58%, NHL = 41%
• OTHER KEY SAMPLE CHARACTERISTICS: Conditioning regimens: MM = HD melphalan, NHL = BEAM (carmustine, etoposide, cytarabine, melphalan)

• SITE: Single site, 0
• SETTING TYPE: Inpatient  
• LOCATION: Instituto Carlos III, Spain

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

• Retrospective

• Primary outcome measurement was development of OM (time to onset, severity/duration, and resolution), on the World Health Organization (WHO) mucositis grading scale.
• OM assessed by nursing team on day 1 prior to ASCT and days 3, 6, 9 and 12 after ASCT.

Oral mucositis was significantly lower in the intervention group (44%) compared to the control group (82%) (p < 0.001). Grades III and IV oral mucositis were also lower in the intervention group (15%) compared to the control group (31%) (p = 0.031). There was no difference between groups in the onset or duration of mucositis.

OC is more effective than oral saline rinses in the prevention of OM, including grades III-IV OM in patients receiving conditioning regimens.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Unintended interventions or applicable interventions not described that would influence results 
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Other limitations/explanation: Conditioning regimens were not homogeneous.

OM can interfere with nutrition and quality of life and can lead to secondary infections. Effective prophylaxis is needed to have good outcomes. Although this study had limitations, OC reduced severity of OM, is cost effective, and is well tolerated by patients. Therefore, it does offer an effective and inexpensive supportive measure.

To evaluate the impact of daily use of 2% chlorhexidine washcloths on the incidence of vancomycin-resistant enterococci (VRE) colonization.

The incidence of VRE colonization among oncology inpatients was examined before and after the introduction of daily use of chlorhexidine-impregnated washcloths. Each day, patients were given four impregnated washcloths, which were used individually for cleaning different parts of the body. Rectal swabs were taken on all new admissions and weekly during the inpatient stay. The baseline period was March to June 2010, and the experimental period was July to October 2010. Patients were in single rooms, although patients colonized with resistant organisms were roomed together. Prior bed occupancy with a patient colonized with VRE was used as a covariate in analysis.

• The study examined 439 total patients (229 at baseline and 210 experimental).
• Males comprised 63.5% of the sample, and females comprised 35.5%.
• Key disease characteristics were not stated.
• Preliminary data showed that 12% of patients became colonized with VRE during the hospital stay.

• Single site
• Inpatient
• Australia

Patients were undergoing the active antitumor treatment phase of care. 

This was an observational study with a historical control. 

• VRE isolates
• Methicillin-resistant Staphylococcus aureus (MRSA) isolates

During the baseline period, 7.8% of the previously uncolonized patients acquired VRE, compared to 3.8% during the experimental period (relatve risk [RR] = 0.48; 95% confidence interval [CI] [0.21, 1.09]). There was no significant effect of prior bed occupants with VRE on VRE acquisition. Patients who shared a room with a VRE-positive patient had significantly higher VRE rates (p < 0.001). There were no significant differences in central line-associated bloodstream infection rates, and few MRSA isolates were found.

The findings do not support the effectiveness of using chlorhexidine-imgregnated washcloths for the reduction of VRE colonization.

• Risk of bias (no control group, no blinding, no random assignment)
• No information was available regarding treatments, tumor types, and aspects associated with risk of infection or use of any prophylaxis for infection prevention.  
• At one point, the researchers stated that patients had private rooms unless colonized, and then they reported that sharing a room with a colonized patient increased the risk, which does not make sense.

The findings from this study do not support the effectiveness of using chlorhexidine-impregnated washcloths to prevent VRE colonization.

To examine the effects of a home-based walking program on quality of life and fatigue.

Women were randomized to the usual care, wait list control, or intervention groups. Those in the intervention group received a 30 minute in-person counseling session and follow-up telephone counseling calls in weeks 1, 2, 4, 7, and 10. Counseling calls applied constructs of social cognitive therapy, discussing specific behavior change principles that could be used to increase walking, using a semi-structured script. Walking plans were designed for gradual increases in frequency, duration, and intensity. Women in the usual care group were asked to maintain their usual activity levels. Those in the intervention group were asked to keep daily activity logs and were given pedometers.

• N = 32  
• MEAN AGE = 55 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All had breast cancer, stages I–III. All had completed adjuvant treatment within the last 12 months.

• SITE: Single site  
• SETTING TYPE: Home  
• LOCATION: South Carolina

• PHASE OF CARE: Transition phase after active treatment

• RCT

• SF-36^®
• Physical activity logs
• Pedometer
• International Breast Cancer Study Group QOL Core Questionnaire
• Functional Assessment of Cancer Therapy–Fatigue
• Community Health Activities Model Program for Seniors (CHAMPS) questionnaire

Fatigue declined in all patients. There was a greater decline among the intervention group, but the difference was not significant. Estimated activity level of walking METs was not significantly different between groups at baseline, but levels post-intervention are not reported. Overall, participants in the intervention group completed 86% (range = 62%–100%) of prescribed walking sessions.

Findings suggest relatively good adherence to home-based walking prescriptions and suggest that this activity may improve fatigue symptoms.

• Small sample (< 100)
• Baseline sample/group differences of import
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Questionable protocol fidelity
• Other limitations/explanation: No measures were taken to check phone follow-up fidelity. Fifty percent of patients in the control group were African American, compared to only 10% in the intervention group. The intervention group was almost twice as large as the control group.

Findings suggest that a prescription for a home-based walking program can be a practical way to improve or maintain physical activity among women with breast cancer after initial treatment, and that this activity can improve symptoms of fatigue. There were multiple limitations to this study; however, multiple studies have shown that exercise is effective to reduce fatigue. Previous findings regarding self-managed exercise programs have been mixed. This pilot study suggests that a prescription for exercise, patient counseling and follow-up contacts may facilitate performance of home-based exercise.

The purpose of this study was to evaluate a compounded topical gel containing baclofen 10 mg, amitriptyline HCL 40 mg, and ketamine 20 mg in a pluronic lecithin organogel (BAK-PLO).
 

Participants were randomized to receive 1.31 g of a compounded gel containing 10 mg of baclofen, 40 mg of amitriptyline HCL, and 20 mg of ketamine versus an identical looking placebo gel. Instructions were to apply one level spoonful of gel topically to each area of pain, numbness, and/ or tingling, twice a day (in the morning and before bed), for four weeks duration. Participants were not allowed to treat more than four areas of pain, numbness, and/or tingling at a single time (i.e., a maximum of four spoonfuls of gel per application). A small subset of participants was asked to have blood drawn at the end of the four weeks to measure concentrations of drugs and their metabolites.

• A total sample size of 203 patients (62% female) were assigned to either an intervention group or control group.
• The mean age of the intervention group was 59.9 years (SD = 10.75) and 62.1 years (SD = 10.27) in the control group; the age difference was not statistically significant.
• Disease characteristics were not provided, although it was clear that the patients had cancer.
• About 90% of the participants were Caucasian with chronic neuropathic pain for more than three months in duration.

The study was conducted at 16 separate academic institutions in the United States.

Phase of care

• Active treatment  

Applications

• Late effects and survivorship
   

The study was a double-blind, randomized, placebo-controlled trial.

• The European Organisation for the Research and Treatment of Cancer QLQ-C30 to measure quality of life.
• The CIPN20 to measure peripheral neuropathy.
• The Brief Pain Inventory to measure pain.
• The Profile of Mood States to measure mood.
• The National Cancer Institute's Common Terminology Criteria for Adverse Events.

Significant improvements in neuropathy symptoms in the hand and functioning of the hands were identified. Results in the feet were not as marked. Systemic absorption was minimal. Analysis of change in sensory neuropathy showed an effect size of about 0.28 (Cohen’s d, p = 0.053) in favor of the intervention. For the measurement subscale for motor neuropathy, the effect size of the change from baseline was 0.38 (p = 0.021). When analyzed as an ordinal scale outcome variable of negative change, no change or positive change for neuropathy symptoms, no significant difference was found between groups. No differences were noted between groups in the mood, pain, or quality-of-life measures.

Topical application of baclofen, 40 mg of amitriptyline HCL, and 20 mg of ketamine may be a useful approach to treatment of neuropathic pain related to CIPN, particularly if pain in the hands exists.

A limitation of this research was that the authors could not get U.S. Food and Drug Administration approval for the doses they originally wanted to use because of limited data on systemic absorption.

 Nurses may consider use of this novel topical compound, but more data is needed before definite recommendations can be made.

To assess the effect of a standardized preparation of valerian in improving sleep in patients undergoing therapy for cancer.

Patients receiving therapy for cancer who reported sleep difficulty of 4 or greater on a scale of 0 to 10 with a life expectancy of more than six months and an Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1 were included. Patients were randomized to receive 450 mg of oral valerian or placebo to be taken one hour before bed for eight weeks. Valerian capsules used contained 0.8% of valerenic acid. Valerian and placebo capsules were stored together so the placebo capsules would have a similar smell to the valerian capsules. Study measures were completed at baseline and four and eight weeks. Toxicity was assessed every two weeks using the Common Terminology Criteria for Adverse Events (CTCAE).

• The valerian group included 20 men and 80 women. The placebo group included 15 men and 85 women.
• In total, 119 patients were evaluable for the final endpoint.  
• Mean age was 59.5 years (standard deviation [SD] = 11.95 years) in the valerian group and 58.3 years (SD = 12.71 years) in the placebo group.
• Primary tumor sites included breast, colon, prostate, and other. Breast cancer was the most common diagnosis.
• Patients were in active treatment, including radiotherapy, parenteral chemotherapy, oral therapy, combined therapy, and planned or concurrent hormone therapy.
• Tumor status included resected with no residual tumor, resected with known residual tumor, and unresected.
   

• Single site
• Unspecified

Patients were undergoing the active treatment phase of care.

The study was a randomized, controlled trial.

• Pittsburgh Sleep Quality Index (PSQI)    
• Functional Outcomes of Sleep Questionnaire (FOSQ)
• Profile of Moods States (POMS)
• Brief Fatigue Inventory (BFI)
• Symptom Experience Diary (SED)
• CTCAE, version 3.0
   

Total PSQI scores were not significantly different between the two groups over time. Although fewer patients in the valerian group reported sleep problems at week 8 than patients in the placebo group (64% versus 80%), no statistically significant changes in sleep problems were observed from baseline to week 8 in either group. Amount of sleep was significantly improved in the valerian group from baseline to week 4 (p = 0.008), but not from week 4 to week 8. Statistically significant improvement was observed in the valerian group in sleep latency, and 43% of patients reported reduced time to fall asleep compared to 32% of patients in the placebo group.

The Fatigue Inertia subscale of the POMS was significantly different from weeks 4 (p = –0.004) and 8 (p = 0.02), with better scores reported in the valerian group. The valerian group also scored significantly better from baseline to weeks 4 and 8 on the Fatigue Now subscale (p = 0.003 and p = 0.01, respectively) and the Usual Fatigue subscale (p = 0.02 and p = 0.046, respectively) of the BFI.

No significant differences were observed between groups for self-reported side effects at any of the data collection points. The placebo arm reported a significantly higher incidence of grade 1 alkaline phosphatase toxicity (p = 0.049).

The study showed that valerian provides no statistically significant improvement in sleep quality in patients undergoing treatment for cancer. Additional study on the effects of valerian on daytime fatigue may be warranted.

• The study had a sample size of less than 100 patients per arm, which the authors reported may be insufficient for statistical power.
• The study did not compare valerian use to other treatments directed at insomnia, such as cognitive-behavioral therapy or benzodiazepines.

The study findings do not support the use of valerian in patients with cancer and insomnia. Additional study is needed to determine the effects of valerian on fatigue in this patient population.

The purpose of the study was to examine the effect of vitamin E in breast cancer survivors.

Participants received an eight-week supply of study medication (400 IU of vitamin E succinate or placebo twice daily) labeled with the days and weeks for dosing.

One hundred twenty-five (125) women aged  33–67were randomized; 5 participants on the placebo-arm withdrew before starting study medication, which resulted in 120 patients assessable for toxicity. One hundred five (105) participants completed five weeks of study; 104 finished all nine weeks.  

• Inclusion criteria:
  • Older than age 18 with a history of breast cancer
  • Must have had hot flashes for at least one month with a frequency of at least 14 times per week.
  • Life expectancy of six months or more and an ECOG performance status of 0 or 1 
  • Tamoxifen use allowed
• Exclusion criteria:
  • Current or planned therapy with chemotherapy, androgens, estrogens, progestational agents, corticosteroids, or other agents used for treating hot flashes not allowed
  • Women who took more than two multivitamin tablets per day or more than 60 IU of vitamin E daily  
  • Pregnant or lactating women, those with a history of bleeding, immune deficiencies, or thrombophlebitis

In this placebo-controlled, randomized, crossover trial, women were stratified by age (18 to 49 years and 50 years and older), current tamoxifen use (yes or no), duration of hot flashes (less than 9 months versus 9 months or more), average frequency of flashes (2–3 per day, 4–9 per day, or 10 or more per day), and current multivitamin use (yes or no).

Baseline hot-flash counts for each woman were obtained for the first seven days. Starting the second week and for the remaining seven weeks, study medication was taken, and the women continued to keep a daily diary of hot flash severity and frequency.

Treatment efficacy was measured using three variables: mean daily hot-flash frequency, mean daily hot-flash severity (grades 1 to 4 to representing mild, moderate, severe, and very severe), and mean daily hot flash score (frequency times average severity). All factors were measured during the last week of each treatment and compared with baseline week. The 105 participants who finished the first treatment period showed a similar reduction in hot flash frequencies for the two study arms. (25% versus 22%; p = .90). This effect represents an average decrease of roughly 1.6 hot flashes per day to a level of 4.7 hot flashes per day. The hot flash score decreased by 28% with vitamin E and 20% with placebo (p = .68). A crossover analysis, however, showed that vitamin E was associated with a minimal decrease in hot flashes (one less hot flash per day than was seen with a placebo) (p ≤ .05). At the study end, participants did not prefer vitamin E over the placebo. No toxicity was demonstrated.

Although this trial was able to show a hot flash reduction with vitamin E compared to a placebo, the clinical magnitude of this reduction was marginal

To evaluate three different doses of citalopram for management of hot flashes

Women were randomly assigned to receive 10, 20, or 30 mg citalopram or corresponding number of placebo pills daily for six weeks. Treatment was titrated weekly to achieve the target dose.

• N = 196  
• MEAN AGE = 55.6 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: 55% were on aromatase inhibitors, and 38% were on naloxifene or tamoxifen.
• OTHER KEY SAMPLE CHARACTERISTICS: The majority had over four hot flash episodes per day.  

• SITE: Multi-site  
• SETTING TYPE: Outpatient  
• LOCATION: United States of America

• PHASE OF CARE: Multiple phases of care

Placebo controlled RCT

• Hot flash scores calculated by assigning 1 (mild) to 4 (severe) points for severity of each daily hot flash episode and adding these scores for a daily hot flash score. 
• Profile of Mood States
• Hot Flash Related Daily Interference Scale
• National Cancer Institute Common Toxicity Criteria version 3.0

There was some improvement in hot flash interference with several areas, and those on 20 and 30 mg of citalopram had significant improvement in sleep interference compared to placebo (p ≤ .01). There were no group differences in overall POMS scores. Adverse effects on sexual health were greater with 30 mg compared to placebo, but this difference was not statistically significant.

Findings show that citalopram in a dose as low as 10 mg daily can significantly improve hot flash symptoms and is not associated with toxicity. Further benefits were seen with higher doses.

• Risk of bias (no blinding)
• Measurement validity/reliability questionable
• Other limitations/explanation: Relatively short duration of treatment, particularly for adverse effects

Findings show that citalopram was beneficial to reduce hot flash severity. The duration of treatment in this study was only six weeks, so longer term efficacy is not clear. Patients on any longer term management with citalopram need to be monitored for side effects of the medication.

To evaluate the efficacy of Wisconsin ginseng on cancer-related fatigue (CRF).

2,000 mg of Wisconsin ginseng or placebo BID (breakfast and lunch) over eight weeks. The assessment conducted at baseline and at four and eight weeks.

• N = 364
• MEAN AGE = 55.3 years for the ginseng group, 55.9 for the placebo group
• MALES: 19% in ginseng group and 25% in placebo group, FEMALES: 81% in ginseng group and 75% in placebo group         
• KEY DISEASE CHARACTERISTICS: Primarily breast (64% in ginseng and 57% in placebo groups) but included colon, prostate, hematologic, gynecologic, and combination/unknown/other cancers having completed or receiving curative intent therapy within past two years and who scored a minimum of 4 on 11-point scale that was present at least a month prior to study entry.
• OTHER KEY SAMPLE CHARACTERISTICS: Some were on active treatment during the study and some were post-cancer treatment.

• SITE: Multi-site  
• SETTING TYPE: Not specified  
• LOCATION: Mostly community cancer centers; location not specified

• PHASE OF CARE: Multiple phases of care

• Randomized, double-blind trial

• Multidimensional Fatigue Symptom Inventory–Short Form (general subscale)
• Profile of Mood States (fatigue-inertia and vigor-activity subscales)
• Brief Fatigue Inventory
• CTCAE (version not specified)

Statistically significant changes in scores for MFSI-SF between ginseng and placebo groups at four and eight weeks was in favor of ginseng, but only among those in active treatment. No differences in BFI scores were noted. Greater benefit reported among patients receiving active cancer treatment versus those who had completed treatment.

The ginseng group had improvements in fatigue scores over four- and eight-week periods without significant toxicities. However, data lacking on selected drug-ginseng interactions.

• Selective outcomes reporting
• Subject withdrawals ≥ 10%

Supports use of (controlled, manufactured) Wisconsin ginseng to modify CRF; however, more research is needed to determine how to maximize positive effects. It appears that ginseng effects may only be seen during active treatment.

Evaluate ginkgo biloba for the prevention of cognitive decline associated with adjuvant treatment for breast cancer

Patients were randomized to receive 60 mg of ginkgo biloba or a matching placebo twice a day starting before the second cycle of thermotherapy and continuing throughout treatment and 1 month beyond chemotherapy completion. Participants were stratified by type of chemotherapy, age, menopausal status, and lymph node involvement. Data were collected at baseline before the first or second chemotherapy cycle, during chemotherapy, at the first visit after chemotherapy (1 month), and at 6, 12, 18, and 24 months post-chemotherapy.

• A total of 210 participants were enrolled in the study.
• The median age was 50 years.
• The sample was 100% female.
• All participants had newly diagnosed breast cancer and were chemotherapy naïve. 
• All were receiving adjuvant chemotherapy. About 80% were receiving doxorubicin/cyclophosphamide with or without taxanes.
• 42% of the women were post-menopausal. 
• 94% of the women were Caucasian.

• Multi-site  
• Outpatient 
• 23 institutions in the United States

Participants were receiving active antitumor treatment.

Double-blind, randomized, placebo-controlled study

• High-Sensitivity Cognitive Screen (HSCS)
• Profile of Mood States (POMS)
• Cognitive subscale of the Perceived Health Scale (PHS)
• Common Terminology Criteria for Adverse Events (CTCAE) grading of adverse events
• Trail Making Test (TMT) A and B

No significant differences were seen between groups over 24 months in any study measures. All cognitive test scores improved from baseline to the first chemotherapy follow-up and then stabilized.

The study does not support the use of ginkgo biloba for prevention of cognitive impairment resulting from chemotherapy treatment in women with breast cancer.

• A risk of bias existed because of the very homogenous sample.
• The measurement validity and reliability was questionable because use of the same cognitive measures repeatedly could have resulted in improvement from practice effects.

Findings do not support the use of ginkgo biloba to prevent cognitive changes resulting from chemotherapy in patients with breast cancer.

To compare gabapentin to a placebo on three factors: efficacy in decreasing CINV, tolerability to the medication, and impact on quality of life.

• Day 1: 20 mg of dexamethasone and a 5HT3 receptor antagonist
• Days 2 and 3: 8 mg of dexamethasone two times per day with or without a 5HT3 receptor antagonist
• Day 4: 4 mg of dexamethasone two times per day with or without a 5HT3 receptor antagonist

• Day 1: One tablet (300 mg gabapentin/placebo) in the evening
• Days 2 and 3: One tablet (300 mg gabapentin/placebo) two times per day
• Days 4 and 5: One tablet (300 mg gabapentin/placebo) two times per day or three times per day

• N = 413
• AGE ≥ 50 years (73% in the gabapentin arm, 72% in the placebo arm)
• MALES: 30%, FEMALES: 70%
• KEY DISEASE CHARACTERISTICS: Breast, lung, colorectal, gynecologic, and hematologic cancers among others
• OTHER KEY SAMPLE CHARACTERISTICS: Performance status of 0–2, chemotherapy naive for highly emetogenic and moderately emetogenic chemotherapy; able to swallow pills; first cycle of chemotherapy

• SITE: Multi-site    
• SETTING TYPE: Outpatient    
• LOCATION: United States

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

This phase 3 study was a placebo-controlled trial that was randomized and double-blinded.

• The patients kept a nausea and vomiting diary
• Numeric analog scales were used daily to measure average level of nausea, worst level of nausea, treatment satisfaction, and distress.
• The use of any rescue medications were recorded.
• Satisfaction with treatment and distress were recorded using a numeric analog scale.
• National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) to grade edema, somnolence, dizziness, and ataxia
• Patients used a self-report analog scale to measure loss of appetite, mood swings, diarrhea, fatigue, impaired concentration, and drowsiness.
• Functional Living Index-Emesis (FLIE)

This study did not support the effectiveness of gabapentin as prophylaxis for delayed chemotherapy-induced nausea and vomiting when used in conjunction with dexamethasone and a 5HT3 receptor antagonist.

• Risk of bias (sample characteristics)
• Findings not generalizable
• Other limitations/explanation: The authors defined highly emetogenic chemotherapy as a cisplatin-based regimen; however, several other chemotherapies are also highly emetogenic. Because the authors did not include all high-risk chemotherapies, the sample characteristics may be biased and the findings may not be generalizable to other highly emetogenic chemotherapies.

Based on this study, gabapentin is not recommended as prophylaxis for delayed chemotherapy-induced nausea and vomiting.