STUDY PURPOSE: To assess the effectiveness of glutamine to treat severe mucositis induced by radiation therapy in patients with head and neck cancer

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 5
• TOTAL PATIENTS INCLUDED IN REVIEW = 234 patients with head and neck cancer
• SAMPLE RANGE ACROSS STUDIES: 8–61 patients
• KEY SAMPLE CHARACTERISTICS: Patients receiving radiation therapy for head and neck cancer

PHASE OF CARE: Active antitumor treatment

APPLICATIONS: Elder care

Glutamine treatment had statistically significant benefits: It (a) reduced the risk and severity of OM (grade IV) (RR = 0.17, 95% confidence interval [0.06, 0.47]) and (b) shortened the duration of OM by 2–3 days. The studies reviewed had a low risk of overall bias.

The protective effects of glutamine for radiation and chemotherapy-induced mucositis are promising. Glutamine or alanyl-glutamine accelerated the mucosal recovery through increasing mucosal tissue glutathione stores, reducing inflammatory parameters and speeding re-epithelization.

• Limited search
• Limited number of studies included
• Low sample sizes

Large prospective, comprehensive clinical trials are needed to investigate the effectiveness of glutamine in the prevention of OM induced by radiation therapy or chemoradiotherapy.

• FINAL NUMBER STUDIES INCLUDED = 16
• TOTAL PATIENTS INCLUDED IN REVIEW = 305 
• KEY SAMPLE CHARACTERISTICS: Breast cancer patients only; patients with and without lymphedema

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

The most useful procedure out of those reviewed was lymphatic vessel anastomosis. The least recommended was lymph node transfer because of conflicting data and potential complications. The remaining reviewed options would be effective based on individual cases and needs.

1. More research on lymphatic vessel anastomosis determining the ideal population and parameters for its use is needed.
2. Better definitions of outcomes and a more specific focus for research and data interpretation are needed.
3. Standards for the diagnosis and treatment of lymphedema must be improved to identify current and potential patients who may need interventions or prevention.

• No noted method to evaluate the quality of the studies being reviewed

The findings of this systematic review showed that initiatives to do primary research and data collection would be useful. This may be an area in which nurses can contribute.

STUDY PURPOSE: To evaluate the evidence for the treatment of lower limb lymphedema in patients with cancer

• DATABASES USED: MEDLINE, EMBASE, LILACS, Science Citation Index, Cochrane CENTRAL, International Society of Lymphology, Australian Lymphoedema Association congress proceedings, and SIGLE
• KEYWORDS: Secondary lymphedema and therapy with medical subject headings (full terms available in article)
• INCLUSION CRITERIA: Randomized, controlled trials and comparative observational studies including at least 50 participants with cancer
• EXCLUSION CRITERIA: Studies with no description of treatment effects

• FINAL NUMBER STUDIES INCLUDED = 7
• TOTAL PATIENTS INCLUDED IN REVIEW = 778
• SAMPLE RANGE ACROSS STUDIES = 18–260 patients
• KEY SAMPLE CHARACTERISTICS: Mixed etiologies of lymphedema and various tumor types

PHASE OF CARE: Late effects and survivorship

The treatments included in this study were compression stockings, coumarin, pneumatic compression devices, microsurgery, manual lymphatic drainage, and an herbal remedy combining coumarin ginkgo and melitoto. There was a high risk of bias among the studies. Various methods of measuring limb volume were used. All studies reported favorable outcomes with a reduction of limb excess volume from 6.8% to 20%. The largest effect was reported with complete decongestive therapy. Some studies included patients with lymphedema etiologies other than cancer. Only one study using each type of intervention was found.

The effectiveness of various treatments for lower limb lymphedema are unclear because of the very limited evidence in this area.

• Low-quality studies
• Very few studies found

There is very little evidence regarding the efficacy of various interventions for lower limb lymphedema in patients with cancer. Lymphedema can be disabling, and effective interventions have not been identified. This is an area in which additional, well-designed research is needed.

To assess whether conducting a larger randomized, controlled trial of aqua lymphatic therapy (ALT) would be feasible and to estimate the extent to which ALT combined with home-based exercise compared with home-based exercise alone would reduce arm disability in patients with breast cancer-related lymphedema

Twenty-five women were randomly assigned to one of two groups, either ALT combined with home-based exercises or home-based exercises alone. Each woman was assessed before the intervention and after the 12-week intervention with pool-based therapy exercises. Arm volume, arm disability, pain, and quality of life were measured.

• N = 25  
• AGE = Control group: 53.4 years (SD = 9.35 years), ALT group: 56.4 years (SD = 9.76 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer-related lymphedema
• OTHER KEY SAMPLE CHARACTERISTICS: In remission from stage I or II breast cancer, wearing a well-fitted compression garment, at least two months after radiation or chemotherapy, and at least six months after surgery

• SITE: Single-site    
• SETTING TYPE: Outpatient    
• LOCATION: McGill University Health Center, Montreal, Quebec

• APPLICATIONS: Elder care, palliative care 

Single-blinded, randomized, controlled pilot study

• Participants' arm fluid volume was measured by water displacement volumetry and circumferential measurements.
• Grip strength was measured using a baseline hand hydraulic dynamometer.
• Pain was assessed using the short-form McGill Pain Questionnaire (MPQ).
• Upper extremity function was measured using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire.
• Quality of life was assessed using the Functional Assessment of Cancer Therapy- Breast Cancer (FACT-B) version 4

No reductions were found in limb volume in either group. Participants in the ALT group showed significant beneficial changes after 12 weeks of treatment, specifically on the Palliative Prognostic Index (PPI) score when compared to the control group (p = 0.025). There were no other significant improvements between groups. Within groups, there were significant improvements pre- and postintervention in healthy arm grip strength (p = .001 for both groups), affected arm grip strength (p = .008 for both groups), DASH scores (p = .016 in ALT group), FACT-B scores (p = .021 in ALT group), and PPI scores (p = .025 in ALT group).

A larger randomized, controlled trial would be feasible. ALT showed significant improvement in grip strength and DASH, FACT, and PPI scores after 12 weeks of ALT treatment. The intervention did not make lymphedema volume worse, and therefore it may be a safe alternative to land-based treatments of breast cancer-related lymphedema.

• Small sample (< 30)
• Other limitations/explanation: Patients with open wounds would not be able to receive this intervention.

In this study, ALT showed no benefit in arm volume reduction over the control group. ALT was, however, effective at reducing pain intensity scores in the experimental group. Nurses should be aware that ALT does not appear to worsen limb volume in women with breast cancer who have been diagnosed with lymphedema, but it also does not improve limb volume. Nurses should note that ALT may be one potential intervention to help reduce the intensity of pain in breast cancer survivors with lymphedema.

To determine the effect of ​coenzyme Q10 (CoQ10) on self-reported fatigue, depression, and quality of life.

Patients were women with breast cancer and planned adjuvant chemotherapy randomized to oral supplements of 300 mg of CoQ10 or placebo, each combined with 300 IU of vitamin E in three daily doses. The intervention began within four days of starting chemotherapy and was continued for 24 weeks. All study assessments were conducted at baseline and 8,16, and 24 weeks. Serum CoQ10 and vitamin E levels were used to measure adherence to the study medications.

• The study included 175 patients with breast cancer (all women) who completed eight weeks and 139 patients who completed 24 weeks.  
• Median age was 51 years (range 28–85).
• Patients were newly diagnosed with breast cancer.

Patients' homes in South Carolina

Patients were undergoing the active antitumor treatment phase of care.

This was a randomized, placebo-controlled, double-blind trial.

The study used multiple instruments with the primary outcome of fatigue:

• Profile of Mood States-Fatigue (POMS-F)
• Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F)
• Linear analogue scale assessment [LASA]-Fatigue.

No significant differences existed between the CoQ10 and placebo arms at 24 weeks for scores on the outcome instruments measuring fatigue. In addition, no significant differences were found on secondary outcomes, such as quality of life measured by the FACT-Brease Cancer (BC) instrument or the ​Center for Epidemiologic Studies Depression (CESD) Scale measuring depression.

Supplementation with conventional doses of CoQ10 led to sustained increases in plasma CoQ10 levels but did not result in improved self-reported fatigue or quality of life after 24 weeks of treatment.

The study suggests that no evidence exists that using standard-dose CoQ10 supplementation to target fatigue in newly diagnosed women with breast cancer is effective in ameliorating treatment-related fatigue.

To assess the clinical effects of megestrol acetate (MA) on anorexia-cachexia syndrome (ACS) via systematic review and meta-analysis

The MEDLINE, Embase, and Central databases were used to find research from 2002–2007. The previous systematic review by Lopez et al. (2004) was used to identify additional references. Reference lists of the studies included were also reviewed.

The search keywords used were neoplasm, cancer, cachexia, anorexia, and megestrol acetate.

Inclusion criteria were:

• Randomization
• Studies of advanced-stage cancer (other than hormone-dependent cancer and ACS)
• An MA intervention compared to a placebo or other drugs
• Clinical studies of ACS or MA
• Study of outcomes such as survival, weight change, and performance status
• Study of quality-of-life parameters such as appetite, nausea, pain, fatigue, depression, well-being, or mood.

There were no language restrictions for the studies included. The review also included conference abstracts. No flowchart or additional description of initial study volume or eliminations was provided. The validity of eligible studies was assessed to ensure intent-to-treat analysis and completeness of follow-up.

Findings were presented for studies in 21 different categories. These categories were defined according to MA dose; outcomes evaluated; and whether MA was dispensed in varying doses, compared to a placebo, or compared to other drugs, with relative risk findings for effect size.

• The final number of included studies was 30. Five of these were abstracts.
• All studies included patients with advanced-stage cancer.
• In most studies, participants had a variety of cancers. In several studies, lung cancer was a criterion for inclusion; several more studies involved head and neck cancer.

Pooled analysis was completed and statistical significance of overall effects was calculated via the Z-test. Homogeneity of results between studies was analyzed with the chi-square test. Results were summarized by GRADE group categorization.

MA administration is associated with appetite improvement, increased probability of weight gain, and a higher probability of delay in deterioration of performance status. The conclusions regarding MA's influence on other symptoms, quality-of-life indices, and performance status were not clear.

There appears to be a dose-response relationship for achievement of weight gain. To obtain improved appetite, it appears that a low dose of MA (160 mg) is as effective as higher doses. At this low dose, there was a beneficial trend compared to the placebo, and a significant effect of a dose increase has not been demonstrated.

The effects of MA are not significantly different than those of glucocorticosteroids. In a previous review, lower-extremity edema in short-term follow-up and potential increased risk of embolic complications in long-term follow-up were identified as adverse effects of MA

Results suggest that MA has a beneficial effect on appetite.
 

• This review included only advanced cancer cases. The role of MA earlier in the course of disease was not addressed here.
• Studies reviewed were found to be of low quality. Due to this, additional randomized controlled trials with MA are suggested.
• It is suggested that further study of MA's role in ACS include determination of the relative value attributed by patients to individual symptoms affected by MA's use.

To evaluate the effectiveness of acupuncture plus self-care versus self-care alone on hot-flashes control in patients with breast cancer

Assignment to either the acupuncture or control group was 1:1. Both groups received an informational booklet about climacteric syndrome and its management and was followed for at least 12 weeks. The acupuncture group also received 10 traditional acupuncture treatment sessions involving needling of predefined acupoints. Quality of life and climatic symptoms were measured at week 12, 3 months, and 6 months.

• N = 190 (105 self-care and 85 self-care plus acupuncture), allocation ratio 1:1 by hormonal therapy (final—completed treatment was 163 with 88 self-care and 83 acupuncture)
• AGE: 31–65 years
• FEMALES: 100%
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: Breast cancer, age 18–65 years, receiving hormone therapy, amenorrhea in a minimum of the last six months, presenting six episodes or more of hot flashes per day
• OTHER KEY SAMPLE CHARACTERISTICS: Accept and sign the informed consent, score greater than 15 on the Greene Climacteric Scale (GCS), PS > 1, active physical activities or relaxation techniques or diet control in group or self-management, not exclusion criteria as chemotherapy or radiotherapy, concomitant drugs for menopause or previous acupuncture in last year

• SITE: Multi-site   
• SETTING TYPE: Multiple settings    
• LOCATION: Five cancer hospitals and one primary care hospital in northern Italy

PHASE OF CARE: Transition phase after active treatment

A phase III, multicenter, randomized, controlled trial with acupuncture and self-care versus self-care alone

• The primary outcome was hot flashes measured with hot flash score (HFS), recorded daily in diaries.
• Symptoms related to menopause and quality of life were the secondary outcomes and were evaluated with the Greene Climacteric and Menopause Quality of Life (MenQoL) scale, consisting of 29 items on a Likert-type scale ranging from 0 (not bothered) to 6 (maximum impact). 
• Adherence to self-care assignment was evaluated in the control visits.
• Different investigators for clinical data collection and acupuncture administration

Mean HFS at week 12, finalizing the treatment, was 22.7 for the control group and 11.3 in the acupuncture group. Differences in mean HFS were 9.3 (95% confidence interval [214.2, 24.4], p < 0.001). A greater reduction in HFSs were observed in the acupuncture group during the basal, third, and sixth month controls for hot flashes, and a similar reduction was found on the GCS-Greene Climacteric Scale. Twelve patients in the acupuncture arm reported mild adverse events (i.e., muscle pain, headache, and one menstrual bleed). No serious adverse events were reported in either group.

The authors demonstrated that acupuncture plus the self-care intervention during 12 weeks was more effective to decrease the hot flashes than self-care alone. All health-related quality of life dimensions were ameliorated except for sexual dimension. The positive affect persisted for six months after intervention.

• Risk of bias (no blinding)
• Intervention expensive, impractical, or training needs
• Subject withdrawals ≥ 10%
• The intervention was applied in a research context that may be difficult to extend to clinical practice.
• Lost to follow-up in control group was ≥ 10%

Because many women with breast cancer are reluctant to take drugs for hot flashes, nurses can give educational and advice about the effectiveness of acupuncture. The self-care booklet may be a useful tool, but additional investigation of its validity in use with women taking medication for hot flash management is needed.

To compare the impact of tramadol to that of dihydrocodone (DHC) treatment on the quality of life (QoL) and performance status (PS) of patients with cancer pain  

Patients received treatment with either tramadol or DHC controlled-release tablets for seven days. Then drugs were switched and administered for another seven days. QoL and PS were measured at baseline, at the 7th day, and on the 14th day of therapy.

• The sample was composed of 30 patients who completed the study; 40 patients were recruited for the study.
• Mean patient age was 70.5 years.
• Of all patients in the sample, 37% were female and 63% were male.
• The majority of patients had had these cancer diagnoses: lung cancer (four patients), colon cancer (four patients), stomach cancer (three patients), and tonsil cancer (two patients).
• Patients were included if they
  • Had received a cancer diagnosis.
  • Were over the age of 18 years.
  • Were opioid-naive.
  • Had no history of drug abuse.
  • Were capable of taking the medications by mouth.
  • Could communicate normally and fill out questionnaires.
  • Were experiencing nociceptive baseline pain intensity of more than 40 on 0–100 scale during nonopioid therapy.
  • Had no renal impairment.
  • Were not pregnant or lactating.

• Single site
• Inpatient
• One inpatient palliative medicine unit
   

• Phase of care: end-of-life care
• Clinical applications: end-of-life and palliative care, late effects and survivorship

Randomized crossover trial

• Visual analog scale, or VAS (0 = no pain, 100 = the worst possible pain), to measure pain intensity at baseline (before administration of analgesics) and during tramadol and DHC treatment (days 1–14)
• European Organization for Results and Treatment of Cancer quality of life questionnaire (EORTC QLQ C-30), an instrument developed for use in international clinical trials in oncology, which includes scales measuring physical, role (work), cognitive, emotional, and social functioning and global QoL as well as symptom-measuring scales relating to fatigue, nausea and vomiting, pain, dyspnea, sleep, appetite, constipation, diarrhea, and finances.   
• Eastern Cooperative Oncology Group (ECOG) scale and Karnofsky Performance Status Score, to measure performance status. (Authors did not describe performance measurement in detail. Performance status is the dependent variable; the independent variables are drug influence, treatment time effect, and interaction of drug and treatment time.)
   

• More patients in the tramadol group (12 patients) used rescue analgesics than did patients in the DHC group (8).
• Nineteen patients preferred DHC treatment, and four patients favored tramadol therapy. Seven patients thought that both analgesics were equally effective.
• ANOVA for functional scales of EORTC QLQ-C30 showed higher scores of emotional functioning in the tramadol group and higher global QoL and better cognitive functioning in the DHC group. Authors noted a trend toward better physical functioning in the DHC group (p = 0.063 for treatment time, p = 0.09 for interaction of drug and treatment time).
• In the DHC group, regarding symptom scales pertaining to drug and treatment time interaction, results of two-way ANOVA showed less fatigue (p < 0.01), pain (p < 0.001), sleep disturbance (p < 0.005), and nausea and vomiting (p < 0.001) and better appetite (p < 0.039).

DHC treatment was associated with better global QoL, cognitive functioning, analgesia, and appetite and with less fatigue, sleep disturbances, nausea, and vomiting. Tramadol therapy was associated with better emotional functioning, less constipation, and fewer financial problems. Performance status deteriorated in both groups.

• The study had a small sample, with fewer than 100 patients.
• The study had a risk of bias due to no control group, no blinding, and no washout period before the drug switch.
• The treatment period for each analgesic (seven days for each) was very brief.

Findings suggest that the decision between tramadol and DHC should be based on each patient's status and symptoms of concern. To date, no other studies have compared tramadol to DHC in patients with cancer-elated pain. Further research would be beneficial.

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

Oxycodone plus naloxone (OXN) appeared to provide similar analgesic effects as oxycodone, but it also improved bowel function, defined as more frequent and complete spontaneous bowel movements and less consumption of laxatives. In addition, OXN improved the passing of urine in patients with postoperative pain while reducing OIBD, improving compliance, and enhancing quality of life. OXN may be administered to opioid-naïve patients with moderate to severe pain and to patients not responding to weak opioids. The evidence from studies of chronic nonmalignant and cancer-related pain demonstrated the role of OXN in the prevention and treatment of OIBD in patients who required opioid therapy for moderate to severe pain. An evaluation of the value of the literature and studies was not evident in this article.

OIBD is a common complication in patients receiving long-term opioid treatment. The use of OXN was demonstrated by a number of studies to be effective for the management of pain and to have a role in the prevention of OIBD in patients with moderate to severe chronic nonmalignant and cancer-related pain.

Demographic characteristics were generally well-balanced between OXN groups and placebo or oxycodone groups. However, there was a larger sample size of patients with cancer-related pain in one specific study that could have altered the results. There was a high rate of variability in the type of studies that were included, and there was no critical analysis of the literature.

OXN appears to provide similar analgesic effects as oxycodone, but it improves bowel function, defined as more frequent and complete spontaneous bowel movements and a less frequent consumption of laxatives. In addition, patients receiving OXN had improved quality of life scores with decreased OIBD complications.

To evaluate the efficacy of the Caring for the Caregiver Program (CCP) to enhance the quality of life of the caregivers of patients diagnosed with advanced cancer compared to caregivers who receive standard care

Participants were randomized to receive the intervention using CCP plus standard care or standard care from home Hospice providers. Two post-test measures were used at four and eight weeks postintervention. The CCP intervention was comprised of a one-hour, face-to-face session to develop a plan of care, a video clip, two follow-up phone calls, and an invitation to join an online social support group.

• N = 56
• MALES: 26, FEMALES: 54
• KEY DISEASE CHARACTERISTICS: Stage IV cancer prognosis of at least three months
• OTHER KEY SAMPLE CHARACTERISTICS: Receiving Hospice care; English-speaking; greater than 21 years old; caregivers spent a minimum of 20 hours a week with patient; most participants were Chinese

• SITE: Home  
• SETTING TYPE: Four home Hospice and one outpatient clinic
• LOCATION: Singapore

• PHASE OF CARE: End-of-life care (stage IV)
• APPLICATIONS: Palliative care 

Pilot-randomized, controlled trial with a two-group pretest and repeated post-test

• The Caregiver Quality of Life Index: Cancer (CQOLC)
• Social Support Questionnaire (SSQ)
• Depression Anxiety Stress Scale (DASS)
• General Closeness Scale (GCS)
• Self-Efficacy in Self-Care Scale (SESCS)
• RC scale
• Caregivers' perceived knowledge of advanced care planning and community resources (six-question Likert scale)

The CCP had a positive effect on family caregivers providing care to patients with advanced cancer.

• Small sample (< 100)
• Risk of bias (no random assignment): Per the author's discussion, random sampling method could lead to selection bias on participant characteristics
• Risk of bias(sample characteristics): Only English-speaking patients were included
• Findings not generalizable: Sample size could limit ability to generalize
• Other limitations/explanation: RC scale was not clearly identified; authors should clearly state the source and validity of this scale

Identifying at-risk caregivers and implementing a CCP intervention can improve the experience of patients with an advanced diagnosis of cancer and their caregivers. These types of interventions have the potential to decrease caregiver strain and burden by improving access to social supports and improving knowledge and self-efficacy.