The objective of the article is to report on strategies that patients with breathlessness find helpful and provide a review of current evidence about the role of nonpharmacologic interventions in managing dypsnea.

This article reports a secondary analysis of data from a trial in which self-report items were used to assess the impact of dyspnea on daily activities, feelings about breathlessness, and strategies adopted by patients. Authors also review the findings of several systematic reviews of nonpharmacologic interventions for breathlessness involving patients with chronic obstructive pulmonary disease (COPD) as well as lung cancer.

• The article reported on a sample of 144 patients.
• The mean age was 67.9 years (SD = 9.6 years).
• The sample was 60% males and 40% females.
• Patients involved in self-report of strategies all had cancer. 
• Most data from systematic reviews involved primarily patients with COPD.

The multi-site study was conducted in an unspecified setting in Australia.

• Patients were undergoing end-of-life care.
• The article has clinical applicability for palliative care.

Descriptive

• Author-designed self-report instrument based on an assessment guide developed in the UK
• Likert-type scoring on a 4-point scale

About half of patients reported that breathlessness had some effect on feelings of panic, fear, and anger. Activity modification was the most frequently used strategy.  Cognitive coping strategies were used by 80% of respondents. Other strategies included breathing exercises and environmental modifications. The most helpful strategies related to activity modification. Of those who used coping and breathing exercises, 60% said they were helpful. Breathing retraining was found to be effective but is mainly studied in COPD. Exercise program findings are inconclusive, and interventions to reduce anxiety have had some positive outcomes. Other interventions such as music, distraction, and complementary medicine have insufficient evidence.

Patients in this study reported that activity management was helpful to manage dyspnea.

• 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) 
• Risk of bias (sample characteristics)
• Measurement validity/reliability questionable
• The likert scale used is questionable in terms of lack of differentiation in terms used for degree of effect.
• Findings reported from systematic reviews were mainly from COPD cases, and few included patients with lung cancer. 
• Other cancers were not included.

Findings suggest that educating appropriate patients about activity management can be helpful for them to manage symptoms of dyspnea. Limited evidence exists about the effects of other nonpharmacologic approaches that are effective for patients with cancer.

PURPOSE: Review evidence and provide guidelines for use of natural agents in the prevention and management of oral mucositis in cancer

TYPES OF PATIENTS ADDRESSED: Patients receiving chemotherapy, radiation therapy, or stem cell transplant

RESOURCE TYPE: Evidence-based guideline

PROCESS OF DEVELOPMENT: Systematic review of evidence, quality rating using Hadorn criteria, and level of evidence classified via Somerfield criteria

DATABASES USED: MEDLINE

KEYWORDS: Alternative, complementary, homeopathic, aloe vera, beta carotene, chamomile, chines herbal, folic acid, and numerous other specific natural agents

INCLUSION CRITERIA: Not specified, other than use of a natural agent

EXCLUSION CRITERIA: Not specified

PHASE OF CARE: Active antitumor treatment

APPLICATIONS: Pediatrics

Ninety-nine papers were identified, and, of these, 49 papers were included in the review.

• Glutamine (20 studies)—not recommended for prevention in patients undergoing hematopoietic cell transplantation. For other situations, no guideline was deemed possible.
• Vitamins A  or E (eight studies)—no guideline possible
• Honey (four studies)—no guideline possible. Each study used a different type of honey.
• Zinc (four studies)—no clear recommendation is given, but the committee suggested it may be of benefit for prevention in patients with oral cancer during radiation or chemoradiation therapy.
• Twelve studies of various other agents were reviewed. No guidelines were possible in any of these.

• Many studies were of low quality, and some were more than 10 years old. 
• Hadorn criteria reliability is questionable. 
• For many products, only one study was found.

Findings do not support efficacy of currently studied natural herbal agents and other agents for prevention of oral mucositis. Systemic zinc supplementation may be helpful for patients with oral cancer receiving treatment. Glutamine is not recommended in patients undergoing cell transplant. Further, well-designed research in this area continues to be needed.

STUDY PURPOSE: To assess the efficacy of compound kushen injection (CKI) for bone pain in cancer

TYPE OF STUDY: Meta-analysis and systematic review

DATABASES USED: MEDLINE, Cochrane Collaboration, four Chinese databases, two Korean databases, and one Japanese medical database

KEYWORDS: kushen, yanshu, matrine, and various terms for bone cancer pain

INCLUSION CRITERIA: RCT, adult patients with cancer-related bone pain; patients in the control group were given radiotherapy, opioids, non-steroidal anti-inflammatory drugs, or bisphosphonates

EXCLUSION CRITERIA: Nonrandomized trials

TOTAL REFERENCES RETRIEVED = 170

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Used the GRADES system for quality evaluation

• FINAL NUMBER STUDIES INCLUDED =  7
• SAMPLE RANGE ACROSS STUDIES, TOTAL PATIENTS INCLUDED IN REVIEW: 521 total patients; sample size per study not reported
• KEY SAMPLE CHARACTERISTICS: Variety of tumor types

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

All studies were done in China at a single center. Analysis showed that CKI relieved pain when compared to bisphosphonates or radiotherapy (RR 1.25, p < .0001). The quality of all studies included was low, and risk of bias was high. Not all studies examined adverse effects. In four studies, patients who received CKI had less nausea and leukopenia. Analysis showed positive results, indicating publication bias.

CKI may have beneficial effects and reduce cancer-related bone pain. However, the small number of trials and low quality of the evidence is insufficient to show efficacy.

• Small number of studies
• Low quality of studies
• All studies done at the same institution

Evidence is insufficient to determine efficacy of the Chinese herbal medicine kushen.

To evaluate the effects of promoting sleep and relieving fatigue of warm-water footbaths for female patients with gynecologic cancer undergoing chemotherapy.

Using a footbath device (40x27x45 cm) with water temperatures at 41°C to 42°C, participants in the experimental group soaked their feet to a depth of 10 cm above the ankle. Participants soaked their feet between 8 and 9 pm for 20 minutes and went to bed within one hour of completing the foot soaking. Participants started the foot soaking the eve of first dose of chemotherapy. Participants in the control group did not soak their feet in footbaths. All participants, those receiving and not receiving footbaths, completed fatigue and insomnia items on days 1, 2, 4, 7, and 14 after each scheduled chemotherapy treatment.

• The sample comprised 43 women (control group, n = 25; experimental group, n = 18).
• Mean (standard deviation [SD]) age was 50.6 years (SD = 11.5) in the control group and 47.6 years (SD = 11.2) in the experimental group. Participants were included if they were between the ages of 20 and 70 years.
• Participants had newly diagnosed cervical, ovarian, endometrial sarcoma, or other gynecologic malignancy.
• Participants were receiving platinum chemotherapy in a four-series regimen. 
• Women were excluded if they had a history of diabetes mellitus and neuropathy, had skin breaks or foot fracture, were receiving Lipo-Dux chemotherapy, were taking any medications that might intensify the effects of peripheral neuropathy, had stage IV cancer, or had severe nausea and vomiting within 48 hours of the chemotherapy.

• Single site
• Outpatient
• Northern Taiwan

Patients were undergoing the active treatment phase of care.

The study used a pre-/post, two-group, prospective, longitudinal cohort design. Control group participants were enrolled and completed measures (no intervention) prior to starting the experimental intervention.

• Brief Fatigue Inventory-Taiwan Form (BFI-Taiwan)
• Verran and Snyder-Halpern (VSH) Sleep Scale, Chinese translation

Fatigue levels, except in the first session, were significantly lower in the experimental group than in the control (p < 0.001).

The experimental group had higher sleep scores (better quality sleep) than the comparison group at every observation point. All differences but the measurement on the first session were significant (p < 0.001).

Warm-water footbaths administered prior to bedtime during chemotherapy improved sleep and fatigue scores in a small sample of Taiwanese women with gynecologic cancer.

• Compliance was monitored by telephone follow-up only. It was not possible to accurately ensure that water temperature, level, and timing were delivered as prescribed.
• The timing of data collection and lack of monitoring calls to the control group was a limitation. Researchers were unable to assess the possible effect of daily telephone calls.
• The study had a small sample size and was conducted at a single site.

A warm-water footbath, also referred to as local moist heat, is a noninvasive, easy-to-administer technique that may improve sleep and fatigue in women with gynecologic cancers. Further study is warranted.

To test the effect of a home-based walking program on symptom distress and mood status in women undergoing breast cancer treatment.

Women referred by their oncologists were randomly assigned to the exercise or control group. Patients in the control group were instructed to maintain their usual lifestyles. Those in the exercise group were given individualized home-based exercise instructions based on American College of Sports Medicine guidelines. Participants were asked to walk briskly three times per week for 12 weeks during chemotherapy treatment, beginning two to three days after starting each chemotherapy cycle. Exercise sessions included a five-minute warm-up, 30 minutes of walking at  60% to 80% of the age-adjusted maximal heart rate, and a five-minute cool-down. Patients were asked to wear a heart rate monitor during exercise sessions and to monitor their own heart rates during exercise. Investigators read the heart rate monitor data weekly. Outcome data were collected at baseline and at six and 12 weeks. All patients received weekly telephone calls over the 12 weeks to identify any relevant health problems among participants.

• The sample was comprised of 40 participants.
• Mean age was 51.8 years (range 31–67).
• All participants were female.
• Most participants had stage I or II breast cancer and were receiving adjuvant chemotherapy.  
• All participants had undergone surgery, and most had undergone modified radical mastectomy.

• Single site
• Outpatient
• Taiwan

Patients were undergoing the active treatment phase of care.

This was a randomized, controlled trial.

• Seven-day physical-activity recall:  self-reported physical activity and intensity (prior validation and reliability provided)
• MD Anderson Symptom Inventory (MDASI)
• Profile of Mood States (POMS), Taiwanese version

Adherence to the exercise prescription was 77% for the number of sessions and 100% for intensity. Mean physical activity levels from self-reports were not different between the groups at baseline. However, over time, a significant effect developed, for time and group assignment, regarding weekly energy expenditure (p = 0.02). Over time, symptoms declined in both groups, and the authors noted a significant group-by-time interaction on symptom severity (p < 0.01), indicating a greater decline in the exercise group. The authors also noted, compared to baseline in the exercise group, a significantly lower symptom severity overall, lower symptom interference, and less mood disturbance (p < 0.01) at 12 weeks. During the same period, the severity of symptoms increased in the control group. The sample size was determined by power analysis and met the size requirements.

Findings suggested that an individually prescribed home-based exercise program can reduce symptom severity and mood disturbance in women with breast cancer during adjuvant chemotherapy treatment.

• The study had a small sample size, with less than 100 participants.
• The authors provided no information regarding medications provided to patients that could have influenced differences in symptoms.
• Patients had relatively low symptom severity at baseline (<3), and individuals with more advanced disease were excluded from the sample.
• The authors did not clarify how critical the weekly telephone calls were to patient adherence to the exercise regimen, and the authors did not detail the nature of these calls.
• This was a single-site study of relatively short duration.

Use of a prescribed individualized exercise regimen consisting mainly of brisk walking, three days per week, was shown to have a positive effect on the symptoms and mood of women with breast cancer during chemotherapy treatments. Although the study did not show the effect on single symptoms, overall symptom severity decreased. This study showed that this type of simple exercise intervention for patients during cancer treatment can have a positive effect for overall well-being.

To compare the efficacy and tolerability of transdermal granisetron to oral granisetron

Patients were randomized to receive either a granisetron patch and placebo capsules or a placebo patch and granisetron capsules. Samples were stratified according to emetogenicity of chemotherapy, gender, and chemotherapy duration. Patches were applied for 24-48 hours before chemotherapy and left in place for seven days. Patients received 1 mg oral medication one to two hours before chemotherapy and then 1 mg every 12 hours throughout chemotherapy.

• N = 313   
• MEDIAN AGE = 59 years, 57 years
• MALES: 61%, FEMALES: 30%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Varied tumor types—lung and gastrointestinal were most common.
• OTHER KEY SAMPLE CHARACTERISTICS: About one-third were chemotherapy naive.

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: China

PHASE OF CARE: Active antitumor treatment

Double-blind, placebo-controlled, parallel group trial

• Complete control (CC): no vomiting or retching, no rescue medication, and no more than mild nausea
• Time to failure of CC
• Complete response (CR): no vomiting or retching, no use of rescue medication

More patients in the oral granisetron group achieved CC (58.97% versus 46.75%, p = 0.04). The biggest difference occurred on the first day of chemotherapy. From days 2–5, no significant difference existed between groups. There were no differences based on gender, age, or emetogenicity of the chemotherapy regimen. More patients taking oral granisetron reported constipation.

In this study, oral granisetron was more effective than transdermal granisetron for control of chemotherapy-induced nausea and vomiting (CINV) during the acute phase.

• Measurement/methods not well described
• Documentation of CINV episodes was not described.
• Other antiemetics recommended for highly and moderately emetogenic chemotherapy were not used.

In this study, oral granisetron was more effective for CINV prevention than transdermal granisetron during the acute phase. In the delayed phase, results were similar for both interventions. It is unclear if the timing of application of the transdermal medication may affect this finding.

Evaluate the efficacy and tolerability of duloxetine in the treatment of chronic oxaliplatin-induced peripheral neuropathy

Patients receiving 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) who had grade 1-2 neuropathy on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v3.0) were given duloxetine at 30 mg/day and escalated to 60 mg/day for one week if there were no signs of drug intolerance. Patients were followed at two-week intervals for laboratory testing, assessment, and evaluation for adverse effects and symptom grading. The study lasted 12 weeks.

• N = 30
• MEAN AGE = 64.8 years (range = 34-83 years)
• MALES = 56.4%, FEMALES = 43.6%
• KEY DISEASE CHARACTERISTICS: All had colorectal cancer; 79.5% had stage IV disease.
• OTHER KEY SAMPLE CHARACTERISTICS: 43% had grade 1 neuropathy at baseline, and 54% had grade 2 at baseline.

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

PHASE OF CARE: Active antitumor treatment

Single-group, prospective, open-label trial

• Visual analog scale (VAS) for peripheral neuropathy pain (10 cm)
• NCI CTCAE v3.0

VAS scores showed improvement in 63.3% of patients who continued on the study for 12 weeks, and 47.4% maintained a stable grade of neuropathy. 28% discontinued duloxetine because of intolerable adverse events, including dizziness, nausea, somnolence, restlessness, insomnia, and urinary hesitancy. No substantive changes in serum creatinine or hepatic enzyme levels occurred.

For those patients who could tolerate escalating doses of duloxetine, it appeared to have some benefit in reducing peripheral neuropathy symptoms.

• Small sample of < 100
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Subject withdrawals ≥ 10%
• 30% withdrew due to inability to tolerate the medication.

Some antidepressants have been studied for their potential effect on chemotherapy-induced peripheral neuropathy. This study suggests that duloxetine may be helpful to some patients; however, the study was limited by a small sample size and open-label design. Thirty percent of the sample dropped out of the study within the first 12-week period due to side effects of the study medication, showing that many patients may not be able to tolerate the drug. Nurses caring for patients with or the potential for peripheral neuropathy symptoms and who are being treated with antidepressants need to assess for patient tolerance of these drugs. Further research is needed to establish the efficacy of antidepressants for peripheral neuropathy secondary to chemotherapy administration.

To evaluate improvementcancer-related pain management after the implementation of a program to improve this aspect of cancer care

The pain initiative involved the training and education of medical and nursing staff, training in standardized cancer pain management according to National Comprehensive Cancer Network (NCCN) and World Health Organization (WHO) guidelines conducted monthly, patient education in person and via booklets, and the use of a pain assessment scale posted at each bedside. Participating hospitals established cancer pain treatment teams including multiple disciplines. Patients who had multiple bone metastases were included. Patients who were cared for after the program was initiated were compared to historical controls. Pain levels were recorded on admission and after pain management.

• N = 475
• AGE = Not reported
• MALES: 57.7%, FEMALES: 42.3%
• KEY DISEASE CHARACTERISTICS: Lung, breast, head and neck, and other cancer types
• OTHER KEY SAMPLE CHARACTERISTICS: The majority of patients had multiple metastatic bone lesions.

• SITE: Multi-site  
• SETTING TYPE: Inpatient    
• LOCATION: China

• APPLICATIONS: Palliative care 

Multisite cohort comparison with historical controls

• Pain reporting rate on admission
• Rate of analgesic administration
• Numeric Rating Scale (NRS) for pain 
• Rate of complete pain remission (pain level decreased to none)

The proportion of patients with pain on admission was higher after the intervention. The complete pain remission rate was higher in the intervention group (54.5% versus 33.7%, p = 0.0002). The uncontrolled pain rate was lower with the intervention group (13.8% versus 31.5%, p = 0.0001). There was greater use of strong opioids after the intervention (p = 0.01). There were no differences between groups in use of bone modifying agents, radiotherapy, or nonsteroidal anti-inflammatory agents.

The organizational intervention used here, including staff education, patient education, and ongoing visual reminders at the point of care, appeared to have a positive effect on pain management practices and outcomes.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias (sample characteristics)
• Measurement/methods not well described
• Questionable protocol fidelity
• Other limitations/explanation: The timing of various pain measurements used in the comparison was not stated. The use of historical controls had some inherent potential bias because of the possibility of other confounding variables although the timeframe between groups was only about six months. The duration of management for individual patients was not stated. The medications used and dosages were not provided.

There is some evidence that cancer-related pain continues to be under-reported and undertreated. The program initiated and reported here was associated with some improvements in practices related to pain management and pain outcomes predominantly associated with the increased use of strong opioids. This program provided an approach to encourage clinicians to pay more attention to pain and increase skills for appropriate analgesic use. It appeared to lead them to use strong opioids more. This evaluation could provide ideas for institutional efforts to improve cancer pain management.

To evaluate the efficacy of an aerobic exercise program for fatigue in women receiving radiotherapy for breast cancer

Patients were recruited to an intervention group and to a comparison group. The intervention consisted of aerobic exercise using a treadmill with mild to moderate intensity defined as 40%–65% of maximum heart rate. Exercise was done for 20–30 minutes three days per week during six weeks of radiation therapy. Fatigue was assessed prior to radiation therapy and then weekly for six weeks.

• N = 47
• MEAN AGE = 50.3 years (SD = 9.5 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All patients had breast cancer. Women receiving chemotherapy and radiation therapy were not included.
• OTHER KEY SAMPLE CHARACTERISTICS: The majority were married and not working outside the home.

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

• PHASE OF CARE: Active antitumor treatment

Two-group, nonrandomized, quasi-experimental study

• Taiwanese Brief Fatigue Inventory (BFI)
• Rate of perceived exertion (Borg scale)

Fatigue trends over time showed a consistent decline in the intervention group and an increase over time in the comparison group. With the intervention, the change in fatigue was -1.09 (p < 0.0001), and in the control group, fatigue increased by 1.45 points by week 6 (p = 0.002). The same pattern was shown for fatigue interference with daily life measures.

The findings of this study suggest that aerobic exercise can reduce and prevent fatigue during radiation therapy. The study's design limits its generalizability and the strength of these findings.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Risk of bias (no appropriate attentional control condition)  
• Subject withdrawals ≥ 10%

This study adds to the body of evidence regarding the efficacy of exercise to combat fatigue during active cancer treatment. This study was conducted during radiation therapy, showing that aerobic exercise can be helpful during this treatment.

To evaluate the efficacy of the triple drug combination of palonosetron, aprepitant, and dexamethasone for chemotherapy-induced nausea and vomiting (CINV) prevention

The antiemetic regimen was 0.25 palonosetron IV prior to chemotherapy, 125 mg aprepitant on day 1 and 80 mg on days 2–3, and 20 mg dexamethasone IV on day 1 and 5 mg dexamethasone IV every 12 hours after chemotherapy. Antiemetic rescue of either diphenhydramine or metoclopramide was used as needed. Nausea and vomiting were recorded daily during hospital stay and by patients daily after discharge. Evaluation was done across two cycles.

• N = 69   
• MEDIAN AGE = 61 years
• AGE RANGE = 32–81 years
• MALES: 61%, FEMALES: 30%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: All were scheduled to receive at least 50mg/m² cisplatin. Patients had varied tumor types, of which esophageal and genitourinary were most prevalent.
• OTHER KEY SAMPLE CHARACTERISTICS: All were chemotherapy naive.

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

• PHASE OF CARE: Active antitumor treatment

• Observational

• Complete response (CR) defined as no emesis and no rescue
• Nausea reported on four-point scale from none to severe (bedridden because of nausea)

The CR rate was 100% in the acute phase and 96.7% in the delayed phase. During the first cycle, the CR rate of no nausea was 98.6% during the acute phase and 87% in the delayed phase. The CR rate reported was exactly the same in the acute phase for the second cycle, and rates for no nausea were similar to those in cycle 1.

The triple drug antiemetic regimen used here was shown to be effective. The CR rates reported here are higher than seen in other studies, and during the acute phase, dexamethasone was given IV rather than PO, as done in most outpatient studies.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement validity/reliability questionable
• Nausea rating and timing not well described

This study aligns with a significant volume of evidence showing the effectiveness of a standard triple drug regimen for CINV prophylaxis in patients receiving highly emetogenic chemotherapy.