To determine pharmacokinetics (PK) and efficacy of oral mesna

Patients were given IV mesna for the first dose and then randomized to IV or oral mesna for the following two doses. Crossover occurred at cycle two.

• N = 7 patients given ifosfamide 2g/m²/day for five days—16 evaluable for POB

• Phase I/II randomized crossover design of IV/oral mesna
• Patients crossed over after first cycle
• Study ran over two full cycles of chemotherapy

• Urine sampling and serum sampling for PK 
• Weekly complete blood counts, serum chemistry, and urinalysis

There were no significant differences in plasma PK between IV and oral. Rates of HC were not significant among IV and oral arms (3 of 16 for IV/IV/IV arm (90% CI 0.15 – 0.34) and 4 of 16 for IV/PO/PO arm (90% CI 0.23 – 0.52). Measurement of HC was not clearly defined.

• Small sample size
• Crossover design gives more power and eliminates P-450 differences—power not addressed and so would decrease in LOE from I to II

To evaluate domicile-based humidification on mucositis symptoms associated with radiation in patients with head and neck cancer

Inpatients were randomized 1:1. The control group (n = 100) received the institutional standard of care for managing mucositis (as defined by each institution), and the intervention group (n = 103) received the standard of care plus domicile-based humidification with the Fisher & Paykel Healthcare MR880 humidifier. The humidifier was set at 37°C and 100% relative humidity. 44 mg of vaporized water per liter of air was delivered via nasal prongs. Sensors were used for continuous feedback and to optimize delivery and prevent condensation. The rate of flow was selected to promote some leakage of moisture into the oral cavity and began at 25 L per minute. Flow was increased 30 L per minute if tolerated by the patient. Humidification began on the first day of radiation therapy with continuous use at night and additional use during the day. The intervention continued for 12 weeks. Patients who had a mucositis score ≥ 2 at week 12 continued the intervention until his or her score was < 2 or until week 16, whichever occurred first. The electronically recorded compliance was set with four hours of daily humidifier use as the benchmark. Data were recorded weekly until week 12 for all patients and weekly until week 16, or until mucositis scores were < 2, for some patients. Additional data were collected at weeks 12 and 20.

• N = 203            
• AGE = Patients were all ages 
• MALES: 164 (80.8%), FEMALES: 39 (19.2%)
• KEY DISEASE CHARACTERISTICS: Head and neck cancer

• SITE: Multi-site 
• SETTING TYPE: Outpatient  
• LOCATION: Eleven participating institutions across Australia and New Zealand

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

Randomized, controlled trial

• National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI, CTCAE) version 3.0
• McMaster University Head and Neck Radiotherapy Questionnaire (HNRQ) 
• MD Anderson Symptom Inventory Head and Neck Module 
• Fiberoptic endoscopic examination

High, medium, and low humidifier compliance rates were reported in 23, 20, and 60 patients, respectively. Per protocol (PP) patients were those in the medium and high compliance groups. The difference in compliance was significant between institutions (range = 0.11–0.74, mean = 0.37, p = 0.004). The mean number of hours the intervention device was used was 3.6 hours (range = 0–14 hours). Differences in the institutions' ​area under the curve (AUC) for mucositis scores ≥ 2 were significant (range = 6.87–11.87, p = 0.008). There was no difference in the AUC in CTCAE scores. There was a difference between groups in PP functional mucositis scores ≥ 2 (p = 0.009) and ≥ 3 (p = 0.006).

Humidification can decrease the severity of mucositis and decrease the time to healing of ulcerated mucositis. Unfortunately, there was a low rate of compliance with the home-based humidification intervention. Patients in the study cited the following reasons for disliking the intervention: dislike of high-flow rate, heat, plastic nasal interface odor or bore size, and noise during the night. The study also showed that patients who reported the highest satisfaction with the humidifier were those who had the most symptom relief from its use.

• Risk of bias (no blinding)
• Other limitations/explanation: High rate of noncompliance with intervention

Patients who were compliant with the intervention saw a reduction in the severity of mucositis and faster healing of oral ulcers. The majority of patients enrolled, however, reported low compliance with the intervention for a variety of reasons. The use of a humidifier at home may appeal to some patients. Nurses can play an important role in assessing if patients are ready to make a life change that includes an intervention such as this one. Patients who were compliant with the intervention reported more symptom relief than patients who were not compliant.

To determine whether cranial electrical stimulation (CES) is feasible for symptom management in patients with breast cancer receiving chemotherapy and to examine the outcomes for reducing the symptoms of fatigue, depression, anxiety, pain, and sleep disturbances in these patients.

Symptom reports (on fatigue, depression, anxiety, pain, and sleep disturbances) were collected at baseline by a research associate and then weekly using an interactive voice response (IVR) phone system. Patients were trained on the use of the CES devices and were able to use them at a setting of 100 ​µA for up to sixty minutes per day. They began using the devices on the first day of their chemotherapy infusions. Patients receiving chemotherapy every two weeks used the CES device for a total of six weeks; those receiving chemotherapy every three weeks used them for a total of eight weeks. A follow-up interview was held after patients finished the protocol.

• The study included 34 women aged 18 years and older (mean = 48.3 years [standard deviation (SD) = 7.9 years]).
• All patients had breast cancer and were receiving chemotherapy.

Multisite

 Patients were undergoing the active treatment phase of care.

This was a prospective, double-blind, three-group, randomized, longitudinal pilot feasibility study.

• Hospital Anxiety and Depression Scale (HADS)
• Brief Pain Inventory (BPI)–short form
• Brief Fatigue Inventory (BFI)
• General Sleep Disturbance Scale (GSDS)
   

Positive correlations existed between all symptoms, except pain and anxiety. Pain and fatigue symptoms were highly correlated with C-reactive protein. 

CES appears to be a safe intervention during chemotherapy. This study showed that CES was a feasible and safe intervention during chemotherapy. It also showed positive correlations between several symptom management variables, but larger studies are needed to determine whether CES is effective for symptom management. 

• Some data were missing due to the ineffectiveness of the IVR system. 
• The study did not describe significant findings about this intervention on pain management in patients with cancer and would not be particularly valuable for the ONS Pain PEP project.
• The study had a small sample size, with less than 100 patients.
• No analysis of outcomes between groups was performed.

The study examined several symptoms seen in patients with breast cancer. Larger studies are needed to examine whether CES has a true effect on pain symptoms in patients with breast cancer.

To examine the effects of cranial stimulation on symptoms

Women were randomly assigned to receive actual or sham cranial stimulation. The device passed biphasic electrical stimulation via ear lobe electrodes. The active device was preset to deliver maximum stimulation at 0.5 Hz and 100 µA, the lowest setting below the level of perception. The sham device was identical but did not transmit a current. Patients were instructed to use the device daily for one hour during chemotherapy treatment and for two weeks after treatment cessation. Symptom data were collected weekly, and patients completed logs to record stimulator use.

• N = 163
• MEAN AGE = 51 years (SD = 0.78 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All participants had breast cancer, and 88.3% had stage 2 disease.
• OTHER KEY SAMPLE CHARACTERISTICS: In total, 61.7% were Caucasian, and 82% had more than a high school education.

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

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

Double-blinded, randomized, sham-controlled trial

• Hospital Anxiety and Depression Scale (HADS)
• Brief Pain Inventory (BPI)
• Brief Fatigue Inventory (BFI) 
• General Sleep Disturbance Scale (GSDS)

There were no statistically significant differences in levels of depression, anxiety, pain, fatigue, or sleep at any time point during the study. Symptom levels were low. Anxiety was highest at baseline and decreased over time. Depression and fatigue increased over time.

This study did not demonstrate any benefit of microcurrent cranial stimulation in the management of pain, anxiety, depression, fatigue, or sleep disturbance among women receiving chemotherapy for breast cancer.

• The patients had low symptom severity, which may have caused the lack of significant changes.
• Adherence to the intervention was measured by patient self-reports.

Cranial stimulation did not benefit symptom management in this study.

To test the feasibility, acceptability, and impact of family-centered advanced care planning for adolescents with cancer

Adolescent/family dyads were randomized to intervention and control study arms. All participants received a baseline assessment and were provided with an advanced care planning educational brochure. Those in the intervention group had five sessions of assessments and interviews and three weekly sessions with a trained or certified facilitator to explore values and beliefs, have conversations, share decision making processes about palliative care and goals, and express fears, values, beliefs, and goals about death and dying. Study measures were obtained at baseline and at three months.

• N = 30 patient/family dyads
• MEAN PATIENT AGE = 16 years (range = 14–20 years)
• MALES: 71%, FEMALES: 29%
• KEY DISEASE CHARACTERISTICS: Leukemia, lymphoma, brain tumors, and other solid tumors; most were receiving cure-directed treatments; those with significant depression were excluded
• OTHER KEY SAMPLE CHARACTERISTICS: 82% were in high school; 12% of families were at or below the federal poverty level; 41% were African American

• SITE: Single site  
• SETTING TYPE: Multiple settings  
• LOCATION: Washington, DC

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Pediatrics and palliative care

Randomized, controlled trial

• Satisfaction questionnaire
• Beck Anxiety Inventory (BAI)
• Beck Depression Inventory (BDI)
• Pediatric Quality of Life Inventory (PQLI)
• Spiritual Well-Being Scale of the Functional Assessment of Cancer Therapy (FACT) scale

Anxiety declined in all adolescents over time. Among families, anxiety declined in those in the control group but increased in families in the intervention group. Baseline depression was significantly lower in the intervention group and increased over time. There were no significant differences between groups from the group and time analysis. There were no significant differences between groups in quality of life results. There were no other differences based on group assignment.

The family-centered advance care planning intervention tested here did not demonstrate any benefits for patients or families in regard to anxiety, depression, or quality of life.

• 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 method to evaluate intervention fidelity was mentioned. There were significant differences between the groups in baseline anxiety and depression scores.

Advance care planning is an important component of care for patients with cancer and their families. However, it might not reduce the emotional effects of the cancer trajectory. This study had numerous limitations and did not find benefit in terms of reducing anxiety or depression. Additional well-designed studies are needed to confirm the findings shown here.

TYPES OF PATIENTS ADDRESSED: Sample not described

PROCESS OF DEVELOPMENT: Study utilized previous Cochrane Systematic reviews along with current references to a United Kingdom national consensus on standards of practice for people at-risk for, or who have, lymphedema (LE)

Evidence weighed using the following classification:

• A = Clear research evidence
• B = Limited supporting research evidence
• C = Experienced common sense judgment.

Recommended for Practice

Complete decongestive therapy

• Patients with LE should receive a coordinated package of care appropriate to their needs (B).

Compression bandaging

• Multilayer inelastic lymphedema bandaging (B)
• Compression garments (C)

Management of infection: Cellulitis/erysipelas

• Criteria for hospitalization
  • Signs of septicemia (e.g., high fever, hypotension, tachycardia, confusion, vomiting).
  • Continuing or deteriorating systemic signs with or without deteriorating local signs after 48 hours of antibiotic therapy.
  • Unresolved or deteriorating local signs with or without systemic signs after first- and second-line oral antibiotics.
  • Close medical follow-up

Exclude other causes of systemic infection, DVT, or dermatologic conditions such as eczema and contact dermatitis.

• Before starting antibiotics
  • Swab any exudates, if present
  • Mark extent of rash and date edge
  • Note any painful or swollen regional lymph nodes
  • Obtain labs for ESR, CRP, WBC, and blood cultures.

Begin antibiotics as soon as possible (recommended for practice).

During bed rest, elevate limb, administer appropriate analgesia, and increase fluid intake.

Avoid simple lymphatic drainage (SLD) and manual lymphatic drainage (MLD). If tolerated, continue compression at a reduced level or switch from compression garments to MLLB.

Avoid long periods without compression.

Likely to be Effective

Manual lymphatic drainage (C)

Prevention of infection: skin care

• Good skin care regimens should be implemented by patients and caregivers in the management of LE (B).
• Use neutral pH soaps to avoid drying.
• Apply emollients. 
• Keep skin folds clean and dry.
• Inspect skin for cuts, scrapes, abrasions, and insect bites.
• Avoid scented products.

Benefits Balanced With Harm

Exercise

• Exercise/movement/elevation (C)
• Breathing exercises (C) 

Prophylactic antibiotics: prevention of infection 

• Patients are advised to travel with a two-week supply of antibiotics if they have a history of lymphedema. 

Effectiveness not Established

Intermittent pneumatic compression (C)

Simple lymphatic drainage (SLD)

Surgery (limited evidence, carefully selected patients may benefit, more research needed)

• Surgical reduction
• Bypass of lymphatic obstruction
• Liposuction/lipectomy

Expert Opinion

Patient education 

• People at risk of lymphedema should be identified early during routine assessment, monitored, and taught self-care (C).
• Patients and caregivers should be offered information about LE and its management.
  • Take good care of skin and nails.
  • Maintain optimal body weight (B).
  • Eat a balanced diet.
  • Avoid tight clothing, watches, and jewelry.
  • Avoid extremes in temperature.
  • Use sunscreen and insect repellent.
  • Wear compression garments if prescribed.
  • Undertake exercise and diaphragmatic breathing exercises.
  • Wear comfortable, supportive shoes.
• Risk factors for upper extremity lymphedema 
  • Surgery of breast with axillary node dissection
  • Scar formation, radiodermatitis from postoperative radiotherapy
  • Radiotherapy to breast
  • Drainage or wound complications
  • Cording or seroma formation
  • Obesity
  • Congenital predisposition
  • Trauma to affected extremity (venipuncture, injection, BP)
  • Taxane chemotherapy
  • Insertion of a pacemaker
  • AV fistula for dialysis
  • Living in or visiting a lymphatic filariasis endemic area
• Risk factors for lower extremity lymphedema
  • Inguinal node dissection
  • Postoperative pelvic radiotherapy
  • Recurrent soft-tissue infection
  • Obesity
  • Vein stripping or vein harvesting
  • Genetic predisposition
  • Intrapelvic or intra-abdominal tumor
  • Thrombophlebitis
  • Poor nutritional status
  • Chronic skin disorders or inflammation
  • Any unresolved asymmetric edema
  • Concurrent illness
  • Immobilization or prolonged limb dependency
  • Living in or visiting a lymphatic filariasis endemic area

Measurement

• Accurate assessment including staging (C)
  • Measurement  of LE
  • Assessment of skin
  • Assessment of vascular integrity
• Patients with LE should receive psychological screening to identify those who require help to cope with the condition and those who require specialist intervention (C).

The purpose of the study was to evaluate colony-stimulating factors (CSFs) administered prophylactically, before the onset of neutropenia or fever, compared with concurrent placebo or untreated controls not allowing any dose escalation.

MEDLINE, EMBASE, and Cochrane Library databases were searched, and hand searches of references from published reports were conducted.

Eight randomized, controlled trials (RCTs), including 1,144 patients receiving chemotherapy for solid tumors (n = 753) or malignant lymphomas (n = 391); studies of patients who were receiving high-dose therapy that required stem cell or bone marrow transplantation (BMT) support or who were being treated for acute or chronic leukemia were excluded.

The overall mean risk of febrile neutropenia was 51% among patients not receiving CSFs, and the overall mean risk of febrile neutropenia was 32% among patients receiving CSFs.

CSFs significantly reduced:

• Febrile neutropenia by 37%
• Documented infections by 6%
• Chemotherapy dose reduction or treatment delay by 20%.

CSFs increased the risk of:

• Bone pain by 15%.

CSFs did not improve infection-related mortality.

The authors concluded that CSFs are effective in reducing the risk of febrile neutropenia, documented infections, and chemotherapy dose reductions or delays, but they increase the risk of bone pain. CSFs had no impact on infection-related mortality.

To determine whether prophylactic treatment with the antidepressant citalopram hydrobromide can prevent major depression in patients undergoing treatment for head and neck cancer

The intervention consisted of 40 mg citalopram hydrobromide (a selective serotonin reuptake inhibitor). Medication began with 20 mg/day for week 1 and increased to 40 mg/day until week 12; after week 12, the dosage decreased to 20 mg/day for one week and then the drug therapy was stopped. Data were collected at baseline and at weeks 4, 8, 12, and 16 as well as at any time during the study.

• A total of 23 patients participated in the study (13 in the intervention group and 10 in the control group).
• Mean patient age was 61 years. The age range was 43–81 years.
• Eleven patients were female, and 12 were male.
• Patients were diagnosed with head and neck cancer only, mostly stage III or IV.
• No group differences existed in patients' age or sex, in tumor grade or type, in location of cancer, or in the number of treatment modalities.
• Patients began cancer treatment (surgery and/or radiation with or without chemotherapy) at baseline.

• Single site
• Outpatient
• Nebraska

Active treatment

Prospective, randomized, placebo-controlled trial with double blinding

• Hamilton Rating Scale for Depression (HRSD)
• Psychiatric interview using Mini-International Neuropsychiatric Interview I (MINI) for depression
• University of Washington disease-specific Quality-of-Life Questionnaire (UW-QOL)
• Clinician Global Impression-Severity (CGI-S) scale for global assessment of depression severity

During the 12 weeks of the study, 5 out of 10 taking the placebo and 2 out of 12 taking citalopram met the cutoff criteria for depression (measured by HRSD). However, the difference was statistically insignificant (Fisher exact test, p = 0.17). At the end of the study, of those receiving citalopram 15% were at least mildly ill in terms of global mood state as measured by the CGI-S scale; 60% of those in the control group were at least mildly ill as measured by the same means. Quality of life, measured by the UW-QOL, deteriorated in both groups from baseline to week 16, but less deterioration occurred in the citalopram group (p = 0.14).

Prophylactic treatment with citalopram hydrobromide may decrease the incidence and severity of depression during head and neck cancer therapy.

• The sample size was small, with fewer than 30 participants.
• Because of the small sample size and the inclusion of subjects from only one setting, the external validity and detection of intervention effect may be skewed.
• A priori sample estimation was set at N = 80, and the sample size of this study was much smaller. (Personnel factors led to early conclusion of the study.) As a result, researchers were unable to draw meaningful conclusions.

The risk of major depressive disorder can be very high in patients with head and neck cancer who are undergoing active treatment. Prevention of depression may be an attainable goal, although more research in this area is needed.

To determine whether prophylactic use of the antidepressant escitalopram oxalate would decrease the incidence of depression in patients receiving primary therapy for head and neck cancer

Patients were randomized and stratified by sex, site, stage (early vs. advanced), and the primary means of treatment (radiation or surgery). During the study, patients received either escitalopram or placebo. This was dosed at one tablet (10 mg if escitalopram) and increased by one tablet during the second week. This was the study dose until week 16. At this point, all patients were “weaned” by 10 mg per week, then “medication” was discontinued. Patients were reassessed at 20, 24, and 28 weeks.

• N = 125 
• MEAN AGE: 63.5 years
• MALES: 118 (79.7%), FEMALES: 30 (20.3%)
• KEY DISEASE CHARACTERISTICS: Newly diagnosed head and neck cancer (newly diagnosed or recurrent stage II–IV epidermoid cancer of head and neck)
• OTHER KEY SAMPLE CHARACTERISTICS: Patient must be willing to participate and must be non-depressed (excluded if cognitively impaired, had advanced cancer or limited life expectancy of less than six months, met diagnostic criteria for mental illness, or undergoing treatment for depression or anxiety).

• SITE: Multi-site  
• SETTING TYPE: Outpatient   
• LOCATION: Nebraska Methodist Cancer Center, University of Nebraska Medical Center

PHASE OF CARE:  Active antitumor treatment

APPLICATIONS: Elder care, palliative care

Randomized, double-blind, placebo-controlled

• Quick Inventory of Depressive Symptomology-Self Rated (QIDS-SR)
• Mini-International Neuropsychiatric Interview (MINI)
• Quick Inventory of Depressive Symptomology-Clinician (QIDS-C)

Prophylactic escitalopram reduced the rate of depression in patients with head and neck cancer undergoing treatment. Rate of depression was 10% with escitalopram and 24.6% among those on placebo (p = .04). The rate of depression was significantly higher in patients receiving radiation as their primary therapy as compared to  surgery. Those patients who received drug reported better overall and health-related quality of life throughout the trial and during three consecutive months following drug cessation. Due to unacceptable side effects of medication, 12.8% withdrew from the study.

Escitalopram used in the setting of head and neck cancer immediately following diagnosis can have a positive effect on depression, possibly preventing depression from occurring. It also positively affects quality of life and ability to cope with cancer treatments, possibly enabling patients to continue with treatments.

Subject withdrawals ≥ 10%

Nurses do not have influence as to what the practitioner prescribes for patients (i.e., escitalopram). However, they can suggest it to practitioners. Some oncology practitioners are reluctant to prescribe anti-depressants, as they feel that this is outside their scope of practice. However, consideration is also generally recommended in professional guidelines. Depression may be underdiagnosed in patients with cancer; nurses can advocate for patients by raising attention to the problem in clinical practice. Initial and ongoing assessments for this patient population is imperative based on the high risk for depression. Results should be reported to the provider so patients who are exhibiting signs of depression can be addressed.

The literature search yielded 4,287 articles. Of these, the review of evidence included of the sample 25 randomized clinical trials, 20 prospective single-arm studies, and four meta-analyses/systematic reviews. No method of evaluation of study quality was described.

• Various fractionation schedules can provide significant palliation of symptoms and/or prevent the morbidity of bone metastases.
• Stereotactic body radiation holds theoretical promise in the treatment of new or recurrent spine lesions, and the task force recommended it be limited to highly selected patients, preferably within a prospective trial.
• Surgical decompression and postoperative radiotherapy is recommended for spinal cord compression or spinal instability in highly selected patients with sufficient life expectancy and performance status.
• The use of biophosphonates, radionuclides, vertebroplasty, and kyphoplasty for the treatment or prevention of cancer-related symptoms does not obviate the need for external beam radiotherapy in appropriate patients.  

• Limited search database
• No stated method of evaluating or grading study quality

This systematic review provides information for nurses about evidence regarding use of radiation therapy for the palliation of pain from bone metastases. It points out that use of bone-modifying agents does not preclude use of radiation therapy. It also points out that for patients with multiple sites of disease-related pain, the use of radiopharmaceuticals may be more useful.