• Two independent authors conducted searches. 
• Data extraction: 102 records were retrieved, 36 abstracts were reviewed, and 12 full-text records were reviewed.
• Seven studies were included in this meta-analysis.
• Targeted data were extracted by authors independently.
• Information collected included demographics, clinic pathology, chemotherapy treatment, efficacy of oxaliplatin-based chemotherapy, and effect of Ca/Mg infusions on oxaliplatin-related neurotoxicity. If a study had more than one grade criteria, only data concerning neurotoxicity incidence graded on the basis of Common Terminology Criteria for Adverse Events (CTCAE) were included.

• FINAL NUMBER STUDIES INCLUDED = 7 studies (4 prospective, randomized, blinded trials ; 3 retrospective clinical trials not blinded or randomized [1 Phase II, 2 phase III]) 
• SAMPLE RANGE ACROSS STUDIES: 27–732 (214 patients in prospective studies, 956 patients in retrospective studies) 
• TOTAL PATIENTS INCLUDED IN REVIEW: Only 1,170 of initial 1,339 analyzed because 2 studies published only a portion of patient results. Final patients included: 1,170 (802 in Ca/Mg group, 368 in control group)
• KEY SAMPLE CHARACTERISTICS: All colorectal diagnoses, four inpatient advanced/metastatic studies, three adjuvant studies. Patients in the Ca/Mg group received before and after oxaliplatin infusions in all studies compared to placebo given or no treatment. Doses or total number of cycles were different. Two studies reported outcomes for acute neuropathy, two for neurotoxicity, one for grade 2 or greater sensory neuropathy, one for toxicity, and one for cumulative neuropathy.

PHASE OF CARE: Advanced

APPLICATIONS: Elder care, palliative care

Meta-analysis indicated that Ca/Mg infusions tended to decrease the incidence of oxaliplatin-induced acute and cumulative neurotoxicity. Based on two studies within this meta-analysis in which patients in the Ca/Mg arm received higher mean doses than patients in the control group, the authors infer that Ca/Mg may enhance patients’ tolerance to oxaliplatin.

• Inconsistent outcomes
• Reliance on CTCAE as outcome measure
• Blinding and randomization not consistent
• Selective outcome reporting 
• Possible bias from several sources
• Data on 214 (18.29%) were from prospective, randomized trials; the remaining data on 956 were from retrospective studies.
• Included those receiving palliative and those receiving adjuvant chemotherapy.
• One chronic neuropathy–related outcome

Ca/Mg infusion tended to reduce the incidence of grade 3 neurotoxicity and total cumulative neurotoxicity in patients with colorectal cancer receiving oxaliplatin. However, these findings must be viewed in light of the heterogeneity of the studies included, differences in neurotoxicity outcome reporting, and recent research studies finding no neuroprotective benefit.

To confirm the effectiveness of the combination of megestrol acetate (MA) and thalidomide for the treatment of cancer cachexia.

Patients were randomly assigned to receive either 160 mg of MA and 50 mg of thalidomide daily or MA alone for eight weeks. Study measures were obtained at baseline and eight weeks.

• The sample was comprised of 93 patients (59% male, 41% female).
• Mean age was 62 years.
• Cancer diagnoses were various tumor types with stage III or IV disease, and 62% of the patients were receiving palliative chemotherapy.

• Single site
• Outpatient
• China

The study has clinical applicability for late effects, survivorship, and palliative care.

This was a randomized, parallel, two-group trial.

• Body weight
• Multidimensional Fatigue Symptom Inventory–Short Form (MFSI-SF)
• European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORT QLQ-C30)
• Visual analog scale (VAS) for appetite
• Grip strength dynamometry
• Serum levels of interleukin-6 (IL-6) or tumor necrosis factor-alpha (TNFα)
• National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0

• Both groups showed improvement in appetite (p < 0.01) and body weight (p = 0.02).
• No significant difference was found between groups in change in appetite.
• Patients receiving both MA and thalidomide showed significant reduction in fatigue, whereas those on MA only had increased fatigue (p < 0.01). 
• Grip strength and IL-6 improved in the patients receiving both drugs compared to those receiving only MA (p < 0.05).
• A portion (7.8%) of the initial sample withdrew because of severe side effects, such as thromboembolism. 
• No difference was found between groups in prevalence of adverse effects.

The combination of MA and thalidomide was associated with improvement in fatigue compared to those receiving only MA. The drug combination was not more effective in treating anorexia and did not show more improvement in body weight.

• The sample size was small, with less than 100 patients.
• The study had risks of bias due to having no control group or blinding.

MA has been shown to have an effect in improving appetite in patients with cancer cachexia, but, as shown, also can have clinically significant side effects. Findings from this study did not show better results for appetite with the addition of thalidomide. This combination appeared to have a positive impact on fatigue. Nurses should be aware that patients taking MA can have side effects, such as thromboembolism, so patients receiving this treatment need to be educated and monitored for adverse events.

To investigate whether sucralfate or aqueous cream reduced acute skin toxicity during radiation therapy to head and neck, breast, or anorectal area (phase A), and to evaluate the effect of hydrogel and dry dressings on most desquamation (phase B)

Patients were randomized into one of six treatment combinations.

1. Aqueous cream/dry dressings
2. Aqueous cream/hydrogel dressings
3. No cream/dry dressings
4. No cream/hydrogel dressings
5. Sucralfate cream/dry dressings
6. Sucralfate cream/hydrogel dressings

Patients randomized to the two creams were advised to apply a thin layer of cream to the treatment area twice daily, from the first day of radiation therapy. All patients were given identical advice about washing the treatment area and provided with a supply of perfume-free soap.

• N = 357 patients remained in study (aqueous cream: 117, sucralfate cream: 120, no cream: 120)
• AGE: Younger than 50 years: 62, 50–59 years: 121, 60–69 years: 103, older than 70 years: 71
• MALES: 95, FEMALES: 262
• KEY DISEASE CHARACTERISTICS: Breast cancer, head and neck cancer, anorectal cancer

• Western General Hospital, Edinburgh, Scotland
• Ninewells Hospital, Dundee, Scotland

• Randomized, controlled double-blind trial

• Baseline skin assessments were recorded, including modified Radiation Therapy Oncology Group (RTOG) acute toxicity scale (assessed at up to seven sites within the treatment field), and a series of erythema readings were taken with a Dia-Stron meter using spectrophotometry. The meter readings in non-irradiated areas were subtracted from those in the treated area. The differences were taken as erythema readings for each patient.
• Patients were asked to complete a quality of life questionnaire (Dermatology Life Quality Index [DLQI]) and a patient diary card, including four Likert scale questions about pain, itching, burning, and sleep disturbance.
• The diary card also required patients to self-assess degree of erythema and desquamation seen within the treatment area using a scoring system.
• All assessments were completed weekly until at least two weeks after completion of radiation therapy or until any skin reaction had totally healed.

Findings presented in the article are phase A only. No consistent differences were found in the severity of skin reactions or levels of discomfort between groups. Patients with higher body mass index, who smoked, or who received concomitant chemotherapy, boost, or bolus during treatment were more likely to develop skin reactions. Sucralfate cream produced significantly lower erythema readings than aqueous cream on adjusted analyses, but the group treated with no cream had even lower readings. No difference was found with survival analysis of time to moist desquamation with treatment cream concurrent chemotherapy, which significantly was associated with worse skin reactions (p = 0.006). Nonsmokers had lower skin toxicity scores than ex-smokers, with smokers having the highest scores for all measures.

No evidence supports prophylactic application of either cream tested for prevention of radiation skin reactions. It is possible to predict which patients are at greatest risk of skin reactions. When consistent skin care instructions to wash with mild soap and water are given, no additional symptomatic benefit is gained by applying cream to the treatment area.

• Cost analysis showed a considerable increase in the cost of supplying sucralfate cream compared with aqueous cream or no cream at all.
• Results apply to a largely Caucasian population (two patients were not Caucasian) and cannot be extrapolated to any other ethnic groups.
• DLQI was found to be a fairly insensitive measure in patients undergoing radiation therapy.
• There was no discussion of the validity and reliability of the modified RTOG scale used for the study.
• The sample size was small for the number of different treatment groups to be analyzed.

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.