To examine the effects of Ama Deus healing energy in reducing anxiety and depression in patients with a diagnosis of stage III ovarian cancer

The study involved three weeks of intervention or control, a one-week wait period, then followed by another three weeks of treatment or control. The intervention group received a hand-mediated energy healing technique called Ama Deus, and the control group received relaxation sessions. The intensity and frequency of the intervention/control were not described. During the first three weeks, 64% received the Ama Deus intervention and 36% received a relaxation intervention. After a one-week break, participants crossed over to receive the other intervention. Data were collected at the first meeting after enrollment (pretest), after completion of the first three weeks (midtest), and after the last session of the second three weeks (post-test).

• The study reported on a sample of 14 patients with stage III ovarian cancer.
• Patients’ ages ranged from 48 to 69 years.

• Single site
• Community hospital setting
• Great Lakes region of the United States

• Patients were undergoing the active treatment phase of care.
• The study has clinical applicability for late effects and survivorship.

A simple crossover design was used, with each patient acting as her own control.

• Beck Depression Inventory (BDI)    
• State-Trait Anxiety Inventory (STAI)

Ama Deus Group 1 had significant reduction in state anxiety, and Group 2 demonstrated significant reduction in trait anxiety. Significant findings in depression reduction were revealed among Group 2 participants. It must be noted that no statistical values or types of statistical methods were reported to support these statements.

The study was poorly designed and reported, so no valid conclusion can be made.

• The study had a small sample size, with less than 30 participants.
• The article was written in first-person narrative.
• References were listed, but no footnotes were provided. 
• Statements were not supported by any scores or statistics.
• Interventions were not clearly described.

Implications should only come from peer-reviewed, professionally written sources.

To describe the course of fatigue in depressed patients with breast cancer and determine the effect of psychodynamic therapy on fatigue

Patients were randomly assigned to the intervention or usual care group. Usual care patients were given written information about local counseling resources and given diagnostic information to provide to physicians who could initiate antidepressants or refer them to a psychotherapist. The experimental group was given dynamic short-term psychotherapy adapted to individual needs.

• N = 106
• MEAN AGE = 52.8 years (SD = 8.8)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All had breast cancer and were diagnosed with depression by structured clinical interview.
• OTHER KEY SAMPLE CHARACTERISTICS: Slighty over half of the participants were married, and over one-third were separated, divorced, or widowed.

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

• PHASE OF CARE: Late effects and survivorship

• Randomized, controlled trial

• Multidimensional Fatigue Inventory (MFI)
• European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) questionnaire
• Hospital Anxiety and Depression Scale (HADS)

Overall MFI, physical fatigue, and reduced activity scores declined over time more in the psychotherapy group (p < 0.02). Depression, fatigue, and quality of life scores were significantly correlated (p < 0.01).

A short psychotherapeutic intervention to reduce fatigue in women with breast cancer was associated with a significant reduction in fatigue over time.

• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Unintended interventions or applicable interventions not described that would influence results
• No information of whether control group patients received any interventions for depression was provided.

The results of this study showed that a psychotherapy intervention to reduce depression also had a positive impact on fatigue, and that fatigue, depression, and quality of life were correlated. These findings point to the importance of identifying and managing depression in patients with cancer not only to reduce depression but to have positive effects on symptoms of fatigue and quality of life.

To evaluate the safety and efficacy of KRN5500 for refractory neuropathic pain in patients with advanced cancer

KRN5500 is an agent that inhibits certain enzymes that may modulate aspects of neuropathic pain. Patients were randomly assigned to receive up to 8 weekly doses of the study drug or placebo. Patients were followed over 14 weeks. Patients were allowed to continue their usual pain treatments. KRN5500 was given in escalating IV doses ranging from 0.6–2.2 mg/m². Study assessments were done at baseline, during weekly clinic visits, and at the end of 14 weeks.

• The study reported on 19 patients with a mean age of 61.7 years (SD = 12.7 years).
• The sample was 52.6% male and 47.4% female.
• Cancer types were not described. The majority of patients had chemotherapy-induced peripheral neuropathy, and most had symptoms in the lower extremities.  
• All patients had mean pain ratings of 6.4 or more on an 11-point numeric rating scale at study entry.

This was a multisite, outpatient study conducted in the United States and Puerto Rico.

• Patients were in the late effects and survivorship phase of care.
• The study has clinical applicability for elder care.

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

• Numeric pain scores and pain medications used were documented daily in patient diaries.
• Adverse events (AEs) were defined according to U.S. Food and Drug Administration guidelines.
• Neuropathic pain was documented.
• Patients completed the 12-item Short Form Health Survey (SF-12).

• The mean number of days of treatment with KRN5500 was 40, and the median total dose was 1.27 mg/m² per week. 
• All of the patients on the study drug experienced at least one treatment-related AE compared to 86% of those receiving placebo. The most frequent AE was nausea and vomiting. No serious AEs were assessed as related to the study drug.   
• Those on KRN5500 had a 24% median decrease in pain rating scores from baseline, compared to those on placebo, who had a 0% change (p = 0.03). 
• No significant differences were found between groups in daily pain ratings from patient diaries.  Other study assessments showed mixed results.

This study provided some initial information regarding safety and efficacy of KRN5500 in a small cohort of patients.

The sample size was small, with fewer than 30 patients.

 No conclusions can be drawn regarding the overall safety and efficacy of this drug. Further research in this area is needed.

To determine the long-term performance of fentanyl buccal tablet (FBT) in the treatment of breakthrough pain (BTP) in opioid-tolerant patients with chronic cancer pain; to assess the safety of FBT and how well patients tolerate it

In the screening phase, which lasted up to one week, patients underwent physical, laboratory, and neurologic examinations to determine whether they tolerated the test dose of FBT. In the titration phase, patients started with a therapy of 200 mcg FBT. Titration determined the effective dose. The study defined an effective dose as one that provided adequate relief from BTP within 30 minutes, without causing unacceptable adverse effects, for two episodes occurring at least four hours apart. Patients entered the 12-month maintenance phase when an effective dose of FBT was determined. In the maintenance phase, patients could take a second FBT.

• The sample was composed of 232 patients in the safety population and 197 patients in the maintenance population.
• Mean patient age was 55.3 years (SD = 12.7 years).
• Of all patients, 122 (53%) were female and 110 (47%) were male.
• The sample consisted of opioid-tolerant patients with cancer and BTP in several categories: 107 patients (46%) had nociceptive pain, 42 patients (18%) had neuropathic pain, and 83 patients (36%) had mixed pain.

• Multisite
• Outpatient
• Forty-seven centers in the United States

Prospective repeated-measure, descriptive study

• Data about adverse events observed by investigators or reported by patients, to measure safety
• Daily diary, to record number of BTP episodes and number of FBTs taken 
• Daily global medication performance assessment scale (0 = poor, 4 = excellent)
• Seven-item scale, which patients were to complete before and one month after starting treatment, to assess medication (Only 25% completed the latter assessment.)

• Of all patients, 42% remained in the maintenance phase for 12 months.
• Clinicians were able to identify a successful FBT dose for 71% of all patients.
• Of all patients, 33% discontinued treatment as the result of adverse events typical of opioids (nausea was the most common). As the result of disease progression, 60 patients died after enrollment in the study.
• Patients tolerated FBT well, and the medication had a favorable safety profile.

Patients tolerated FBT well for the study period, which lasted 12 months. The safety profile of FBT was favorable.

• The study had a risk of bias due to no appropriate control group.
• Not all patients completed all measures.

FBT is a favorable option for cancer patients with BTP and can be used safely over a long period.

To assess the efficacy and safety of a single dose of fosaprepitant (150 mg IV) combined with a 5-HT₃ receptor antagonist and a corticosteroid versus a standard 5-HT₃ receptor antagonist and a corticosteroid for the prevention of chemotherapy-induced nausea and vomiting (CINV)

Patients received fosaprepitant versus placebo with ondansetron plus dexamethasone on day 1. Oral ondansetron and dexamethasone were used. Patients who received fosaprepitant on day 1 received placebo medication on days 2–3, while those in the control group received ondansetron every 12 hours. Rescue medications were allowed at the discretion of the provider.

• N = 1,000   
• MEAN AGE = 59.6 years
• MALES: 40.6% in experimental group, 41.2% in standard group; FEMALES: 59.4% (experimental group), 58.8% (standard group)
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Multiple malignancies
• OTHER KEY SAMPLE CHARACTERISTICS: Patients who were treatment naïve and receiving moderately emetogenic chemotherapy (MEC)

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: Conducted at 125 sites across 30 countries

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

• Randomized, double-blind, placebo-controlled trial

• Nausea and the Functional Living Index-Emesis (FLIE)—the research does not discuss how this was administered.  
• Adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.
• Events of clinical interest (reactions, thrombophlebitis, infusion-site pain, erythema, and induration) were recorded.

Complete response (CR) in delayed phase met superiority for the experimental fosaprepitant group versus the control group (p < 0.001) and for the overall phase (p < 0.001). Both regimens had high CR in the acute phase with no significant differences (p = 0.184). Fosaprepitant was superior to the control group for no vomiting in the overall phase (p < 0.001) and delayed phase (p < 0.001), and the time to first vomiting (p < 0.001). Fosaprepitant group had significantly more “no significant nausea” patients than the control group (p = 0.026).

Fosaprepitant demonstrated superior CR overall to oral ondansetron and dexamethasone alone in MEC regimens. These results are similar to results seen in highly emetogenic chemotherapy. Treatment differences of 0.1% in delayed and overall phases are seen to be clinically meaningful for patients.

• Measurement/methods not well described
• How often instruments were completed is unknown.
• Industry supported trial (Merck & Co, Inc.)
• Several authors are either employed, stockholders, and/or paid consultants of Merck & Co.

Fosaprepitant may be safely used in patients receiving MEC. Further study is warranted.

To compare patient-controlled analgesia (PCA) post-operative pain control by IV morphine versus epidural ropivacaine plus fentanyl analgesia in patients undergoing lower-body oncologic orthopedic procedures attributed to bone malignancy

Patients were assigned randomly. There was no control group.

• N = 70
• KEY DISEASE CHARACTERISTICS: Patients with mild systemic disease and those with non-incapacitating severe disease
• OTHER KEY SAMPLE CHARACTERISTICS: Preoperative pain controlled by non-steroidal anti-inflammatory drugs

• LOCATION: Post-anesthesia care unit and ward in Israel

• Randomized controlled trial

• Numeric rating scale (NRS) (0–10) pain at rest
• Subjective sedation (1 = fully awake to 10 = heavily sedated)
• Subjective feeling of well-being on a numeric scale (1 = feeling bad to 10 = feeling content)

• Subjectively rated pain less in patient-controlled epidural analgesia (PCEA) than IV PCA (p = 0.001)
• Feelings of sedation and well-being evened out over time (post-op day 5).
• Incidence of side effects (e.g., nausea, vomiting, pruritus) higher in IV PCA group

Postoperative ropivacaine plus fentanyl via PCEA reduces pain better and affords better subjective feelings than morphine IV PCA after resection of bone malignancy carried out under combined general and epidural anesthesia.

• Only pain intensity at rest reported (patient remained immobile 48–72 hours)
• The effect of improved pain, sedation, and well-being on long-term rehabilitation was not studied.
• Cost was not assessed.
• In the United States, prophylactic venous thrombotic event (VTE) treatment would be avoided with a PCEA.
• Small sample size

To determine safety and tolerability of increased doses of desmopressin (DDAVP) as well as what dose is most effective for cancer surgery, and to monitor the surgical bleeding, the plasma levels of the von Willebrand factor (VWF), and the circulating tumor cells (CTC).

Patients were divided into five groups of four. The patients received two IV infusions, first 30–60 minutes before surgery and again 24 hours later; if there were no dose-limiting toxicities noted, then the next group of patients had increased dosages. Desmopressin was diluted into 100 ml of normal saline. If no dose-limiting toxicity was reported, then the next cohort of patients were given higher doses of medication with the endpoint of a total dose at 2.0.

• N = 20  
• AGE RANGE = 36–62 years
• MEDIAN AGE = 47 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Patients with breast carcinoma stage 0-II
• OTHER KEY SAMPLE CHARACTERISTICS: Treatment included mastectomy or lumpectomy as primary treatment including sentinel lymph node biopsy.

• SITE: Multi-site    
• SETTING TYPE: Outpatient    
• LOCATION: Argentina

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

• Open-label phase II trial concentrating on dose escalation of perioperative DDAVP and looking at surgical bleeding, plasma levels in VWF, and circulating tumors

• The measurement included biochemical analysis and real-time quantitative reverse transcription-PCR looking at CTC and immunhistochemical detection of breast tumor samples
• PRISM 6 6.0.1 was used for statistical analysis.

Of the 20 patients that were enrolled the study, two patients had reversible adverse events. One patient experienced hyponatremia, nausea, and grade 1 dyspnea one hour after the first dose of DDAVP. The second patient experienced grade 2 hypersensitivity reaction, and the medication was interrupted. The rate of the administration was slowed down in additional cohorts to prevent further reactions. A 50% reduction of intraoperative bleeding was noted with the increasing doses of DDAVP, measured by the number/weight of pads used during the procedure. There was also a higher VWF plasma levels and a noted postoperative decrease in CTC counts.

Using 2.0 (mcg/kg) dose of DDVAP was deemed as safe with two slow IV infusions before and after surgical procedures. Using higher doses of DDVAP showed a reduction in intraoperative bleeding, higher circulating VWF levels, and a decrease in CTC counts after the procedure.

• Small sample (less than 30)

Nurses administering DDVAP need to be aware of the potential reactions that may occur with the use of this medication.

To determine the effectiveness of several treatment options in decreasing cetuximab-induced skin exanthema in three study populations: the historic group (no standard skin treatment); the proactive skin therapy group; and the reactive skin therapy group

• N = 50
• AGE = Not reported
• MALES: Not reported, FEMALES: Not reported
• KEY DISEASE CHARACTERISTICS: Gastrointestinal adenocarcinoma, Union for International Cancer Control (UICC) stage 4 
• OTHER KEY SAMPLE CHARACTERISTICS: All patients had a history of receiving chemotherapy (either FOLFIRI or FOLFOX) in combination with a standard dosing of cetuximab (initially 400 mg/m² and thereafter 250 mg/m² weekly). None of the patients received radiation therapy. None of the patients had a history of acne. The patient decided whether he or she would receive the reactive therapy or the prophylactic therapy. 

• SITE: Multi-site  
• SETTING TYPE: Not specified  
• LOCATION: Several cities (Mainz, Darmstadt, and Heidelberg) in Germany

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

Retrospective analysis

• National Cancer Institute Common Terminology Criteria for Adverse Events (NCI, CTCAE) v3.0 criteria
• Physical exam
• Digital photography

• In comparing time to onset of ≥ grade 2 exanthema, all three groups were at one to four weeks. Average time to onset was 14.7 days for group A, 13.2 days for group B, and 13.9 days for croup C.  
• In comparing maximum exanthema (grades 0–I versus 2, 3, and 4), results showed a significant difference between groups A and B (p = 0.027) and between groups A and C (p = 0.069). However, there existed no significant differences between groups B and C (p = 0.69).  
• In comparing frequency of therapy interruption, group C (historic cohort) showed a frequency of 40% discontinuation of cetuximab therapy compared to 0% in group A and 7% (n = 1) in group B. 

Using this simple reactive skin protocol can prevent the exacerbation of cetuximab-induced follicular exanthema. This therapy can stabilize exanthema development. Results of the prophylactic skin treatment cohort showed equally effective, but not superior, results in preventing skin toxicity ≥ grade 2. Both groups B and C had lower therapy interruptions.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (sample characteristics)
• Findings not generalizable
• Other limitations/explanation: Sample characteristics were not identified (e.g., male, female, age). The algorithm for the prophylactic skin protocol on page 1,669 did not match the protocol described in the text (e.g., the algorithm included vitamin K1, which was never discussed in the text). The algorithm had cleansing syndet and topical metronidazole in the row of grade 2, but this info should have been in the box for grades 0–1. Likewise, vitamin K1 and minocycline should not have been in the grades 0–1 box.

Nurses need to assess for exanthema, which generally develops within one to four weeks of initiating cetuximab. Prophylactic and reactive skin protocols are equally effective and may be easier to handle in practice. Both prophylactic and reactive skin treatments reduce higher grades of exanthema, which can lead to therapy cessation.

To assess the effectiveness and safety of alvimopan, a peripherally acting mu-opioid receptor antagonist, in patients with noncancer pain and opioid-induced bowel dysfunction.

Patients were randomized to one of four groups: oral alvimopan 0.5 mg twice daily (n = 130), oral alvimopan 1 mg daily (n = 133), oral alvimopan 1 mg twice daily (n = 130), or placebo capsules (n = 129).

Patients were instructed to discontinue laxative use. Rescue laxative medication (bisacodyl 10-30 mg) could be taken if the patient experienced discomfort with no bowel movement (BM) for four consecutive days. An interactive voice response system via touch-tone telephone was used for number of BMs, associated symptoms, rescue laxative use, opioid consumption, and pain intensity.

• The study reported on a final sample of 333 patients aged 18 years or older.
• Mean patient age was 49.7 years in the alvimopan 0.5-mg twice daily group, 51.5 years in the alvimopan 1-mg daily group, 48.6 years in the alvimopan 1-mg twice daily group, and 51.3 years in the placebo group. 
• The sample was 64% female and 36% male.
• Patients had noncancer pain and an opioid regimen equivalent to at least 30 mg of oral morphine for at least one month prior to screening.
• Back pain was the primary pain condition.
• Patients with neuralgia, fibromyalgia, arthritis, joint pain, and headache were also included.

• Multi-site
• Patients' homes and 113 centers in 9 countries

This was a phase IIb, randomized, double-blind, placebo-controlled, parallel-group study.

• Patient Assessment of Constipation Symptoms (PAC-SYM)
• Patient Assessment of Constipation Quality of Life (PAC-QOL)
• Numeric Pain Scale (0 = no pain; 10 = worse possible pain)
• Modified Himmelsbach Withdrawal Scale to measure signs of withdrawal

• Change in frequency of spontaneous bowel movements (SBMs) during the first three weeks of the treatment period was greater in all alvimopan groups versus the placebo group (p < 0.001).
• Mean weekly frequency of SBMs was significantly greater during the treatment period for all alvimopan groups versus the placebo group (p ≤ 0.01), as was the overall mean change in SBMs (p < 0.001).
• On the first day of treatment, 31% of patients in each alvimopan group had at least one SBM, compared with 18% in the placebo group (p < 0.05).
• Seventy-seven percent of patients in the alvimopan 0.5-mg twice daily group and 75% in both the 1-mg daily group and the 1-mg twice daily group had an increase from baseline of at least one SBM per week, compared with 55% in the placebo group (p ≤ 0.001).
• Individuals in the alvimopan treatment groups versus the placebo group reported moderate or substantial opioid-induced bowel dysfunction global improvement during the treatment period (p ≤ 0.003).
• All alvimopan groups reported improvement in bowel  evacuation throughout the treatment period (p ≤ 0.009).
• Reports of pain or total daily dose of opioid did not change significantly throughout the study.
• All groups had stable scores on the Himmelsbach Withdrawal Scale.

Oral alvimopan increases the frequency of SBMs and improves symptoms in adults on opioid pain regimens.

• The study did not include patients with cancer; therefore, the results cannot be generalized to that population.
• The amount of opioid taken by participants was only the equivalent of at least 30 mg of oral morphine daily.
• After withdrawals, the treatment groups were below the calculated sample size of 125 to achieve 90% power. For patients who withdrew from the study and did not have complete data sets, the last recorded observations for each endpoint were carried forward.

Oral alvimopan may be effective for the treatment of opioid-induced constipation in patients taking opioids for chronic pain and may improve opioid-induced bowel dysfunction symptoms. Use of alvimopan does not appear to compromise analgesia or induce opioid abstinence. Additional study is necessary to look at efficacy with an oncology population and determine long-term efficacy, as well as an optimal dosing regimen.

RESOURCE TYPE: Expert opinion

DATABASES USED: Not included

INCLUSION CRITERIA: Patients treated with ipilimumab

PHASE OF CARE: Active antitumor treatment

Low grade diarrhea (grade 1) should be treated symptomatically using loperamide, oral hydration, and electrolyte substitution. A colitis diet is recommended. Persistent or higher-grade diarrhea, bacterial or parasitic infections, viral gastroenteritis, or the first manifestation of an inflammatory bowel disease should be ruled out by an exam. Oral diphenoxylate hydrochloride and atropine sulfate four times a day and budesonide 9 mg daily are recommended. An endoscopy is recommended. For grade 3 or 4 diarrhea, treatment with ipilimumab should be permanently discontinued, and IV steroids and replenishment of fluid and electrolytes IV should be administered.

The information included was recommended in 2012. Since then, much more has been learned about the treatment of immune-related side effects of checkpoint inhibitors. Steroids are started early. This information seems out of date, and a more recent publication should be used for this specific type of side effect (immune-related colitis).

Patients who receive checkpoint inhibitors experience immune-related side effects that require immune suppression to manage. This is different from the management of diarrhea caused by other treatments for cancer. Nurses need to be aware of this specific cause of similar symptoms and be knowledgeable about its management.