To assess the long-term safety of fentanyl sublingual spray for breakthrough cancer pain

An initial titration phase was used to determine dosing for new patients. Additional patients were continued on the medication after their involvement in a prior double-blind randomized trial. The study was conducted for 90 days. Follow-up was conducted by telephone 30 days after trial completion or patient withdrawal. Study measures were obtained monthly.

• N = 163
• MEAN AGE = 53.6 years
• MALES: 47.6%, FEMALES: 52.4%
• CURRENT TREATMENT: Combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Not provided
• OTHER KEY SAMPLE CHARACTERISTICS: 20% were undergoing chemotherapy. Most had mild to moderate background pain and breakthrough episodes moderate in intensity for a duration of 60 minutes, which occurred a mean of three times daily.

• SITE: Multi-site
• SETTING TYPE: Not specified
• LOCATION: United States, Canada, and India

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

• Open label

• Adverse events
• Treatment Satisfaction Questionnaire for Medication (TSQM)

Of the patients, 80% achieved an effective dose during titration. The median effective dose was 600 mcg, and the range of daily dosing during maintenance was 140–9,381 mcg. Three patients had adverse events possibly related to the study medication, and 7.4% had application site irritation during the titration phase, but no patients had this problem during the maintenance phase. In addition, 87% were satisfied to extremely satisfied with effectiveness of the analgesia during the maintenance period.

Findings suggest that fentanyl submucosal spray is well tolerated over several months of use.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• No measurement of efficacy for pain—study objectives were just to evaluate safety

Findings suggest that submucosal fentanyl spray is well tolerated for relatively long-term use.

To evaluate outcomes after video-assisted thoracic surgery pleurodesis among intubated patients and unintubated patients under local anesthesia

Consecutive patients who received unintubated video-assisted pleurodesis were matched with patients who preferred general anesthesia and were intubated for the procedure. Data were obtained from a retrospective review. Cases were matched on age, gender, performance status, history, and type of tumor. Patients with extrathoracic metastases were excluded. Patients received intercostal blocks and sedation with remifentanil. For the intubated group, general anesthesia was induced with propofol, fentanyl, and vecuronium. Talc was used for pleurodesis in both groups. Postoperative management was the same in both groups.

• N = 462–231 (intervention group)  
• MEAN AGE = 64.3 years
• MALES: 55%, FEMALES: 45%
• KEY DISEASE CHARACTERISTICS: Multiple tumor types with secondary pleural malignancy; most common was lung cancer followed by breast cancer

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

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

Retrospective, descriptive study with a matched control comparison

• European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ C30)

Anesthesia time (p < 0.0001) and recovery room time (p = 0.0002) were significantly shorter in the unintubated group. Postoperative hospital stays were 1.8 days shorter on average in the unintubated group (p = 0.011), and postoperative morbidity (p = 0.042) and mortality (p = 0.017) were lower in the unintubated group. Pleurodesis was successful in more than 83% of patients in both groups, and costs were lower in the unintubated group. Physical function (p < 0.05) and dyspnea (p < 0.01) were more improved in the short-term among the unintubated patients. There was a higher rate of major subcutaneous emphysema in the unintubated group. There were no differences between the groups in effusion-free time or overall survival.

Video-assisted pleurodesis under local anesthesia without the need for intubation was associated with shorter postoperative hospital stays, fewer short-term postoperative issues, and improved dyspnea compared to similar patients who received traditional pleurodesis under general anesthesia.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Other limitations/explanation: The study included people with good performance statuses, so findings may not be applicable to those with poorer physical conditions overall.

The performance of pleurodesis under local anesthesia with video-assisted thoracic surgery was shown to improve short-term postoperative outcomes compared to procedures done under general anesthesia in this study. There were some differences in postoperative complications between patients who had general anesthesia versus those who did not, so nurses need to be aware of the potential differences in complications according to the type of procedure done and assess patients accordingly. The applicability and safety of this approach in patients with very poor overall performance status is not clear.

To investigate the use of acupuncture for the relief of dyspnea

Patients were randomized to acupuncture alone, morphine and acupuncture, or morphine alone groups. Patients in the acupuncture alone arm were provided morphine for rescue if needed. Oral morphine at 2.5 mg every four hours with breakthrough doses were given to the morphine group. In the combination group, patients received morphine before acupuncture. Study measures were conducted at 30 minutes, 90 minutes, 4 hours, and on days 2, 7, and 14.

• N = 145, 175 in intent-to-treat analysis 
• MEDIAN AGE = 73 years
• MALES: 65.1%, FEMALES: 44.9%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Non-small cell lung cancer or mesothelioma
• OTHER KEY SAMPLE CHARACTERISTICS: The baseline mean visual analog scale (VAS) for dyspnea was 6.5.

• SITE: Single site   
• SETTING TYPE: Not specified    
• LOCATION: United Kingdom

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Palliative care 

Three-group, randomized trial

• Forced expiratory volume measured during the first second of forced breath (FEV1)
• Peak expiratory flow rate (PEFR)
• Hospital Anxiety and Depression (HADS) scale for anxiety
• Borg Dyspnea Scale
• European Organization for Research and Treatment of Cancer (EORTC) QLC-30 questionnaire for quality of life
• Visual analog scale (VAS) dyspnea and anxiety

No difference existed between groups in VAS dyspnea scores from baseline to after the interventions. VAS scores for anxiety declined in the acupuncture-only group (p < 0.001) and the combination group (p < 0.001) compared to the morphine-only group by day 14. At 30 minutes, Borg Dyspnea Scale scores were lower in the groups receiving acupuncture compared to the morphine-only group (p = 0.003). Twenty-one percent of patients receiving acupuncture took morphine as a rescue medication.

Acupuncture may play a role in the management of dyspnea in patients with advanced lung cancer; however, additional research is needed to determine efficacy and determine how it is best provided.

• Risk of bias (no blinding)
• Measurement/methods not well described
• Intervention expensive, impractical, or training needs
• Subject withdrawals ≥ 10% 
• It appears that acupuncture was provided once, but the timing was not clearly stated.
• Although VAS scores for anxiety showed a response, HAD scale scores did not.

Acupuncture may have some benefit in the management of dyspnea in patients with advanced disease; however, additional research in this area is needed.

To assess the effect of palifermin on mucositis and infection risk according to conditioning regimen used, and to evaluate the effect of palifermin on fibrinogen levels

This is a retrospective study of patients who underwent high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-SCT) because of hematologic malignancies. The authors evaluated the differences between a cohort of patients who received prophylaxis with palifermin and a matched control group of patients who did not receive this agent, and assessed the effect of palifermin on infection risk according to the conditioning regimen used, comparing BEAM, BU-CY, THIO-CY, and HD-PAM conditioning regimens.

• N = 120 (40 with palifermen, 80 in control)  
• MEDIAN AGE = 47 years in palifermin group and 50 years in control group
• MALES: 65% in palifermin group, 55% in control; FEMALES: 35% in palifermin group, 45% in control group
• KEY DISEASE CHARACTERISTICS: Diagnosis of MM in 57.5% of both groups; lymphoma diagnosis in 22.5% of palifermin group and 31.2% of control group; other diagnoses in 20% of palifermin group and 11.3% in control group
• OTHER KEY SAMPLE CHARACTERISTICS: Pretreatment with less than two lines of therapy prior to SCT in 19% of palifermin group and 29% of control group; HD-PAM in 65% of palifermin group and 57.5% in control group; BEAM/BUS in 35% of palifermin group and 42.5% of control group

• SITE: Single site    
• SETTING TYPE: Inpatient  
• LOCATION: Italian transplantation center

• PHASE OF CARE: Active antitumor treatment

Total of 120 patients who underwent SCT from 2000–2009 who either received palifermin prophylaxis or did not receive palifermin (control group)

Weekly blood cultures, serum galactomannan assay, and skin and oral culture swabs were used in afebrile patients. Standard febrile workup was used including blood and urine cultures, chest radiography (CXR), and a CT of the thorax within 72 hours of the onset of fever. Any infection arising during the first 30 days was evaluated. Fever of unknown origin (FUO), pneumonia, febrile gram-positive bacteremia, and CVC-related infections were all evaluated. Mucositis was assessed for all patients using daily inspection and grading according to daily mucositis scoring using Eastern Cooperative Oncology Group (ECOG) Common Terminology Criteria for Adverse Events (CTCAE) criteria. Gastrointestinal (GI) toxicity was deemed as severe if there were five or more stools per day.

Palifermin reduced rates of severe mucositis when evaluation was conducted taking into account conditioning type. There was a significant reduction in the severe mucositis rate in the BEAM/BUS group, whereas there was no significant reduction in the HD-PAM group. Palifermin had no effect on GI toxicity. FUO was significantly reduced in palifermin treated group. A reduction in severe infections (p = 0.06) existed in the BEAM/BUS group. A highly significant reduction in gram-positive infections existed in the BEAM/BUS group but not in HD-PAM group. Rate of patients with fevers was decreased in the palifermin group, but not significantly. A reduction in serum fibrinogen peak levels during the aplastic phase was observed with palifermin in the BEAM/BUS group but not in HD-PAM group.

Palifermin reduced FUO and severe infections unrelated to gram-positive bacteria with a more evident effect after conditioning based on BEAM/BUS. Severe mucositis was also reduced in the BEAM/BUS group but not in the HD-PAM group. The reduction in fibrinogen level substantiates the beneficial effect and may suggest a reduction in risk of mortality.

• Risk of bias (no blinding)
• Retrospective study

Nurses should monitor fever, mucositis, and onset of infection; educate patients on infection prevention and use of medications; and advocate for use of palifermin in high-risk populations, including the elderly, those receiving BEAM/BUS therapy, or heavily pretreated patients.

To determine the risk of lymphedema associated with immediate breast reconstruction compared to mastectomy alone

Patients were screened for lymphedema prospectively, and lymphedema rates were compared between those who had immediate breast implantation, immediate autologous reconstruction, and those who had mastectomy alone. Each breast was considered individually in analysis. Follow-up was a median of 22.2 months.

• N = 616 women with breast cancer, 891 mastectomies
• MEAN AGE = 48 years
• AGE RANGE = 28–81 years 
• FEMALES: 100%
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: Patients with breast cancer who underwent mastectomy and immediate breast reconstruction or mastectomy alone
• OTHER KEY SAMPLE CHARACTERISTICS: Patients with breast cancer with risk of lymphedema; 65% (580 of 891) had an immediate implantation, 11% (101 of 891) had immediate autologous reconstruction, and 24% (210 of 891) had no reconstruction.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Massachusetts General Hospital, Boston, MA

PHASE OF CARE: Late effects and survivorship

Prospective cohort study

Arm measurements were performed preoperatively and during postoperative follow-up using a perometer. Lymphedema was defined as 10% or more arm volume increase compared to preoperative. Measurement was adjusted for body weight.

Overall incidence of lymphedema was 10.58%. Among those who had immediate breast reconstruction, the incidence of lymphedema was 5.13% compared to 26.66% among those with no immediate reconstruction. Both immediate implantation (HR = 0.172, p < 0.0001) and autologous (HR = 0.467, p = 0.0077) were associated with reduced risk of lymphedema compared to no reconstruction. Factors associated with increased risk of lymphedema were a body mass index greater than or equal to 30, axillary lymph node dissection (ALND), and number of lymph nodes dissected.

Immediate implantation reconstruction does not appear to increase the risk of lymphedema compared to mastectomy alone; however, the findings are limited by significant differences in cohort characteristics shown to be associated with lymphedema incidence.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Key sample group differences that could influence results
• Measurement/methods not well described
• Findings not generalizable
• Defining lymphedema as more than a 10% limb volume increase indicate moderate to severe lymphedema; the lower incidence of lymphedema should be cautioned since 5% of limb volume increase has a negative effect on patients’ quality of life. A significantly lower proportion of those in the immediate reconstruction group had a body mass index of greater than or equal to 30 and had ALND (p < 0.0001). Patients in the no-reconstruction group were significantly older, and age at surgery was a univariate predictor of lymphedema hazard.

Nurses should be advised that although immediate reconstruction may not increase the risk of lymphedema, risk reduction for this population should continue.

To evaluate the effect of 0.1% mometasone furoate on a acute skin-related toxicity in patients undergoing breast or chest-wall radiotherapy

Patients were randomly assigned to either 0.1% mometasone furoate cream or an identical-looking placebo cream. Patients were to apply toe cream once daily to the area under treatment not less than four hours before or after radiation therapy. Creams were used throughout the radiation therapy course. No other topical agents were to be used. If the primary physician initiated a medication other than the study agent, the study medication was discontinued and evaluations continued according to the study protocol. Patients were evaluated at baseline and weekly by treatment providers.

• The study sample (N = 166) was comprised of patients with breast cancer.
• Other sample characteristics were not clearly reported.
   

The study took place at the May Clinic in Rochester, NY.

The study used a double-blind placebo-controlled randomized clinical trial design.

• The National Cancer Institute's Common Termonology Criteria for Adverse Events (version 3.0) was used.
• Patient-reported outcomes were measured using the Skindex-16, the Skin Toxicity Assessment Tool, a Symptom Experience Diary (rated multiple skin toxicity signs and symptoms on a 0–10 scale), and a quality-of-life self-assessment.
   

There was no significant difference between groups in the mean grade of provider-assessed radiation dermatitis. The Skindex-16 showed no statistically significant difference between groups. In the Symptom Experience Diary, patients in the mometasome arm reported less burning, itching, and redness (p < 0.02). There was no difference between groups in quality of life.

Topical mometasone furoate was associated with less burning, itching, and redness but did not show any significant effect on overall radiation-induced skin toxicity.

• No demographic data were reported. 
• It is not stated if any patients were also receiving chemotherapy or whether any patients received other topical agents as allowed. 
• The only explanation provided for the 10% dropout rate was discontinuation.

Findings suggest that topical corticosteroid use or mometasone does not significantly reduce the severity of radiodermatitis but may reduce patient symptoms of burning, itching, and redness. Though topical steroids may not prevent dermatitis, their use may help patients be more comfortable during radiation treatment.

To evaluate the rate of lymphedema occurrence in patients who recieved a mastectomy and a sentinel lymph node biopsy (SLNB) with radiation therapy (RT) compared to an axillary lymph node dissection (ALND) with or without RT, with a secondary purpose to identify risk factors for development of lymphedema

• N = 627  
• MEDIAN AGE = 50 years (range = 22–85 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Individuals who underwent mastectomies after a diagnosis of primary breast cancer between September 2005 and February 2013.

• SITE: Single-site  
• SETTING TYPE: Not specified  
• LOCATION: Massachusetts General Hospital in Boston, United States

• PHASE OF CARE: Multiple phases of care

Pre/post design with repeated measures

• A perometer was used to measure arm volume.
• Weight-adjusted arm volume change (WAC) was used to detect arm volume change in each arm individually.
• Lymphedema was defined as a measurement of ≥ 10% WAC.

Avoiding completion ALND and receiving SLNB with RT may decrease lymphedema risk in patients requiring a mastectomy. This study indicates that the application of the American College of Surgeons Oncology Group's Z0011 treatment protocol may reduce the risk of lymphedema for patients who receive a mastectomy.

• Risk of bias (no random assignment)
• Key sample group differences that could influence results
• Other limitations/explanation: The group that received SLNB without RT was small (n = 34). Less than half (44%) of patients who received SLNB without RT had a positive SLNB. This was a single-site study.

The study provides nurses with information about SLNB with RT and how its use may decrease the risk of developing lymphedema compared to patients who recieve ALND. However, the nonrandomized, controlled trial design and the different sample sizes of each study group limit the ability to generalize this study's findings. Future randomized, controlled studies are warranted.

• Databases searched were MEDLINE and CINAHL (1990-2002).
• Search keywords were nausea, vomiting, chemotherapy and neoplasm, assessment, management, complementary therapies, pharmacological, and nonpharmacological.
• Studies were included in the review if they included primary research, literature reviews, opinion articles, and information leaflets/booklets.
• Studies were excluded if they involved anticipatory nausea and vomiting associated with chemotherapy, because the authors felt that symptoms with a psychological basis should be addressed in a separate paper.

• Nonpharmacologic management interventions were reviewed with the intention that they do not replace standard antiemetic therapies but, rather, are adjuncts to improve quality of life (QOL).
• Intervention articles were reviewed for progressive muscle relaxation, guided imagery, self-hypnosis, acupressure/acupuncture, transcutaneous electrical nerve stimulation, biofeedback, cognitive distraction, and music therapy.

Support for the use of nonpharmacologic interventions for the treatment of chemotherapy-induced nausea and vomiting (CINV) was weak.

Many studies were flawed because of small sample sizes and confounding variables (e.g., stage of disease, various chemotherapy regimens, culture, patient compliance).

Preliminary available evidence suggests positive benefits through nonpharmacologic techniques; however, larger randomized trials are needed to demonstrate the exact benefits, including economic.

The intervention was a 75-minute supportive-affective group that met monthly offering Life-Threatening Illness Supportive-Affective Group Experience (LTI-SAGE). These groups were for education and support, not group therapy. Topics included

• Group dynamics and expectations
• Recognizing and asserting needs
• Feelings and emotions
• Symptom control
• Living well while ill
• Intimate relationships
• Spiritual needs
• Asking for help
• End-of-life care planning/decision making
• Legacy
• Hope
• Group closure.

Groups consisted of three to eight patients, with one or two group facilitators.

Two measurements were taken: baseline and 12 months

In the intervention group (n = 37), group assignment was based on diagnosis and race.

In the control group (n = 32), patients received quarterly mailings of existing, readily available self-help resource materials, with a phone call to ensure that mailings were received.

The study reported on a sample of 69 African American and Caucasian patients with any serious medical condition severe enough to create a limited life expectancy (not cause death within six months).

The study was a randomized pre/post-test trial with a longitudinal design.

• Beck Depression Inventory
• State-Trait Anxiety Inventory (STAI)
• Death Distress Scale
• Spiritual Well-Being Scale
• Illness Disability Index
• Perceived Social Support Inventory
• Analysis of covariance
• Statistics done in two ways: intent-to-treat basis (with the seven noncompliant patients) and also with the seven noncompliant patients removed from the intervention group

• In the intervention group, 7 patients attended 3/12 groups and 21 patients attended 9/12 groups.
• There were no significant statistical differences between groups in anxiety levels. The intervention group did enjoy reduced depression, increased spiritual well-being, and reduced death-related feelings of meaninglessness; p level set at 0.10.
• STAI stats: t(40) = 0.8 with p value 0.40 at baseline
• SSAI postintervention: p = 0.70

• The study had a small sample size.
• Not all patients were diagnosed with cancer.
• The intervention required specially trained facilitators to teach groups.

• FINAL NUMBER STUDIES INCLUDED = 8
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,356
• SAMPLE RANGE ACROSS STUDIES = 40–496 patients 
• KEY SAMPLE CHARACTERISTICS: Most study participants had advanced cancer, all were in palliative care, and all were adults over the age of 18 years. Various corticosteroids were used in studies including dexamethasone, methylprednisolone, and betamethasone. Range of doses (dexamethasone-equivalent doses) ranged from 3–25 mg per day via various routes including oral and IV. One study included the use of metoclopramide, one included the use of megestrol, and four studies included use of a placebo.

PHASE OF CARE: End-of-life care
 
APPLICATIONS: Palliative care

All studies showed an improvement in appetite with the specific steroid used in the study. Side effects were an issue for continued treatment and led to attrition of rates between 16% and 63%. Improvement in appetite was shown to continue through up to eight weeks of therapy. Side effects were a common cause of attrition.

Corticosteroids can be beneficial in treating anorexia in patients with malignancies who are in the palliative care setting. There is inadequate data to recommend a specific steroid over another or a specific dose of the steroid for the management of anorexia.

Various steroids, various routes of administration, and various doses were used, making it difficult to make any conclusions. Steroids are associated with significant side effects including gastrointestinal bleeding, oral candidiasis, and proximal myopathy.  

Anorexia is a significant problem in individuals with cancer, especially in certain malignancies and at the end of life. Nurses need to be aware of potential treatment options and side effects of these treatments to enhance patients' quality of life.