To evaluate the efficacy of a regimen of three-day aprepitant, a single dose of palonosetron, and three-day dexamethasone in patients receiving cisplatin-based, highly emetogenic chemotherapy (HEC)

Patients were given the following regimen. On day 1, patients were given 0.25 mg IV palonosetron, 20 mg IV dexamethasone, and 125 mg oral aprepitant before chemotherapy; on day 2, they received 80 mg oral aprepitant and 4 mg oral or intramuscular dexamethasone; and on day 3, they were given 80 mg oral aprepitant and 4 mg oral or intramuscular dexamethasone.

Rescue therapy was 10 mg metoclopramide and 4 mg dexamethasone. Patient diaries were used to record emesis, use of rescue medication, and severity of nausea for 5 days after chemotherapy.

• The study consisted of 222 participants.
• Median age was 62 years, with a range of 22–82 years.
• The sample was 23.4% female and 76.6% male.
• The most frequent diagnoses were lung, head and neck, stomach, and bladder cancers.
• Patients with stage IV disease represented 77.5% of the sample.
• All patients were chemotherapy naïve and receiving HEC.

The study was conducted in multiple outpatient settings in Italy.

All patients were in active treatment.

This was a prospective trial.

• Patients rated nausea severity on a 4-point Likert-type scale.
• The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ30) was used.
• Complete response was defined as no emetic episodes and no use of rescue medication.

• The majority of patients (70.3%) had complete response, and 92.8% did not have vomiting but did use rescue medication.
• More than half of patients (59.9%) did not experience any nausea, and 31.1% experienced mild nausea.
• Nausea was the main reason for use of rescue medication.
• No major adverse events with antiemetics were seen.
• Patients reporting constipation represented 39% of participants, and headache was reported by 5%.

Palonosetron in combination with aprepitant and dexamethasone was found to be effective in preventing acute and delayed nausea and vomiting with HEC.

• The study did not have an appropriate control group.
• Data for complete response were analyzed only for the overall phase with no subgroup analysis for acute and delayed symptoms.

The findings confirmed the efficacy of palonosetron as part of an antiemetic drug regimen for patients receiving HEC.

To evaluate whether the antiemetic efficacy of triple combination aprepitant, palonosetron, and dexamethasone could be sustained for up to six cycles of highly emetogenic chemotherapy (HEC) (cisplatin ≥ 50 mg/m²)

To be eligible, patients had to be chemotherapy-naïve adults with lung cancer, have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0–2, and be receiving 4–6 cycles platinum-based therapy (cisplatin ≥ 50 mg/m²).

All eligible patients received 125 mg oral aprepitant, 0.25 mg IV palonosetron, and 20 mg IV dexamethasone before chemotherapy on day 1, and 80 mg oral aprepitant and 4 mg oral or intramuscular dexamethasone on days 2 and 3. Patients recorded all vomiting episodes, any use of rescue medication, and the severity of nausea on 4-point Likert-type scale in diaries for 5 days (0–120 hours) after chemotherapy during all planned cycles.

• The study began with 156 patients, and 118 completed the study.
• The median age of participants was 64 with a range of 33–81.
• The sample was 77% male and 23% female.
• Cancer staging was 74% stage IV and 12% stage IIIb.
• Cisplatin dosing was 46% 75 mg/m² and 41% 80 mg/m².  Patients receiving cisplatin combined with two other drugs represented 87% of the sample.
• Number of chemotherapy cycles planned was 6 cycles (80%) and 4 cycles (18%). The majority (84%) completed their planned cycles.
• Patients were excluded if they had
  • Emesis within 24 hours before starting chemotherapy
  • Noncontrolled metastasis in the brain
  • Previous radiation to the brain, abdomen, or pelvis
  • Concomitant medication with antiemetic activity or known to induce cytochrome P450 enzymes.

The study was conducted at multiple outpatient sites in Italy.

All patients were in active antitumor treatment.

This was a prospective observational study.

• Patients maintained study-specific diaries for 5 days (120 hours) post chemotherapy (up to 6 cycles) using a 4-point Likert-type scale and reporting adverse events. 
• Complete response (CR) was defined as no emetic episodes and no use of rescue therapy during the overall phase of all planned chemotherapy.
• Complete control (CC) was defined as no emesis, no rescue therapy, and no more than mild nausea.
• No grade 3-4 adverse events reported.

• CR rates ranged rom 74.4%-82.0% per cycle, and CC ranged from 74.4%-82.0% per cycle (CI 95%).
• More than 90% of patients were emesis free during all cycles (CI 95%).
• No severe nausea was detected. More than 60% of patients were nausea free during all chemotherapy cycles.
• The authors did not report on acute versus delayed chemotherapy-induced nausea and vomiting (CINV).

The triple combination of aprepitant, palonosetron, and dexamethasone enhanced antiemetic protection during the first cycle and the efficacy was sustained for up to six cycles of cisplatin-based highly emeotgenic chemotherapy (HEC) in patients with lung cancer. The majority (84%) of patients were able to complete their planned number of chemotherapy treatment cycles.

• Study limitations include the risk of bias because the study had no control group, no blinding, and no random assignment.
• The measurement and methods were not well described.
• The measurement validity and reliability was questionable.
• Forty patients were lost to attrition by cycle 6.

Patients with advanced stage lung cancer treated with HEC who are given CINV prophylaxis according to accepted guidelines prior to each cycle maintain the benefit from the CINV prophylaxis through all cycles of treatment. Managing the distress caused by CINV may increase overall quality of life and is an important consideration when treating patients with palliative chemotherapy.

To compare Bepanthen cream with no topical ointment

Patients used Bepanthen on one side of the treatment field and used no topical treatment on the other side. Patients were instructed to not inform the physician of which region or field received the application of the cream, and they randomized their own application. Bepanthen twice a day began on day 1 of radiation therapy. Skin assessments were performed weekly during treatment and two weeks following treatment.
 

• The study sample (N = 79) was comprised of patients with breast (n = 63) and T1 and T2 N0, M0 laryngeal (n = 16) cancer.
• Median age of patients with breast cancer was 55 years, with a range of 31–78 years. Median age of patients with laryngeal cancer was 69 years, with a range of 51–85 years.
• Patients with laryngeal cancer received definitive radiation therapy at 2 Gy/fraction and total dose of 70 Gy.
• Twenty-one patients with breast cancer received low-dose cyclophosphamide, methotrexate, and 5-fluorouracil during radiation therapy at cobalt-60 and total dose of 50 Gy.

The study used a quasi-experimental blinded trial design.

• The European Oncology Radiation Therapy Consortium and Radiation Therapy Oncology Group acute skin reaction scoring was recorded weekly, two, and six to eight weeks following treatment.
• Erythema was chosen as the primary efficacy variable.
• Wilcoxan-Signed Rank-Test was used for the primary and secondary efficacy variables.
• Logistic regression analysis was performed to examine the effect of concomitant chemotherapy, skin type, gender, age, and upper verses lower area (for patients with breast cancer only).

For both cancers, all skin reactions were more severe at completion of six weeks of radiation treatments, which was chosen as a reference point to standardize assessment data. No significant difference was observed in erythema, most desquamation, itch, or pain. No significant effect of any of the variables was found in regression analysis regarding erythema and desquamation.
 

Bepanthen did not provide any significant benefit.

• In patients with breast cancer, there were many different techniques of radiation therapy administration and use of bolus.
• No information about patient adherence to the protocol was provided.
• The two groups of cancers treated received different accumulative doses of irradiation.
• Data was not separated for those who also received chemotherapy, which would affect skin toxicity.

Tissue toxicity is associated with 60-cobalt.

The purpose of the study was to examine the superiority in reducing grade 4 leucopenia of pegfilgrastim given on day 4 over giving pegfilgrastim on day 2.

Patients were randomized to receive pegfilgrastim subcutaneously (6 mg) on day 2 or on day 4 in a 1:1 ratio. All sub study patients received intense dose-dense (IDD) chemotherapy consisting of epirubicin 150 mg/m² every two weeks for three cycles, paclitaxel 225 mg/m² every two weeks for three cycles, and cyclophosphomide 2,000 mg/m² every two weeks for three cycles. All received prophylactic oral quinolone antibiotics.

• 355 patients were randomized to receive pegfilgrastim on day 2 (n = 177) or day 4 (n = 178).  
• The median age was 45 years with a range of 24–69 years.
• 100% of the participants were female.
• Female patients biologically younger than 65 years with histologic confirmed, unilateral, or bilateral node-positive breast carcinoma.   
• Patients were required to have adequate surgical treatment with histologic complete resection (R0) of the tumor and greater or equal 10 axillary nodes with primary wound healing and no signs of infection.
   

A single-site setting in Germany

• The phase of care was active treatment.
• The application was for late effects and survivorship.
   

Randomized two-group trial

GAIN (German Adjuvant Intergroup Node Positive) study toxicity grading

The study failed to demonstrate that pegfilgrastim on day 4 was more efficacious than on day 2 with respect to grade 4 leucopenia. For patients receiving epirubicin overall, 11% of patients receiving day 2 dosing had an episode of grade 4 leucopenia during the first three cycles of chemotherapy, compared to 4% of those receiving CSF on day 4 (p = 0.015). There were no significant differences between groups in chemotherapy dose reductions or delays. During cyclophosphamide, significantly more infections occurred in the day 2 administration group (p = 0.035). Across the entire treatment, there were no differences between groups in febrile neutropenia, infections, and treatment alterations.

This study failed to demonstrate that administering pegfilgrastim on day 4 was more efficacious than on day 2 with respect to grade 4 leucopenia (the primary endpoint), febrile neutropenia, or infections.

No blinding
 

The data does not support a change in the current standard dosing schedule; however, it does suggest that administration of colony-stimulating factor on day 4 might be an appropriate alternative to day 2 dosing.

Compare venlafaxine to another nonhormonal agent in the treatment of hot flashes in patients with breast cancer

Patients were randomized to receive 0.075 mg clonidine twice daily or venlafaxine 37.5 mg twice daily for four weeks then crossover.

• Women with breast cancer experiencing hot flashes at least 14 times per week (N = 80). 64 patients completed study 
• Majority older than age 50 years 
• 40 randomized to each group.
  • 33 received clonidine, 31 received venlafaxine 
  • 9 stopped early because of side-effects
  • 7 withdrew
• Inclusion:
  • Adult women with primary breast cancer experiencing hot flashes at least 14 times per week or must have been seeking help for hot flashes. Hot flashes present at least four weeks before study entry.
  • Predefined menopausal status as not required.
  • Tamoxifen, gonadotropin-releasing agonists, and aldose reductase inhibitors  allowed as long as the patients had been on such therapy for at least a month and were planning to continue therapy during study.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Exclusion:
  • Previous treatment with venlafaxine and clonidine as well as estrogens, progestagens, or androgens for hot flashes
  • Current treatment with hypertensive or antidepressant agents, other nonhormonal agents for hot flashes such as black cohosh, isoflavones, and vitamin E 
  • Patients with hypertension or hypotension, peripheral or cardiovascular diseases, or symptomatic cardiac diseases

University hospital setting

Double-blind, randomized study

• Self-reported one-week hot flash and other symptom questionnaire assessed one week before start of treatment and end of treatment.
  • Hot flashes: frequency and severity
  • Symptoms assessed: Loss of appetite, mouth dryness, nausea, tiredness, constipation, restless sleep, nervousness, sweating, dizziness, mood disorder, diarrhea, sleeplessness

At end of week 4, the median hot flash frequency dropped by 7.6 hot flashes per day for patients receiving venlafaxine and 4.85 hot flashes for those receiving clonidine (p = .025). Nausea was significantly greater with venlafaxine compared with clonidine. Mouth dryness, constipation, and restless sleep were reported more with clonidine but the difference was not statistically significant.

• Small sample size with less than 100 participants 
• Short follow-up period

To examine the usefulness of transcutaneous electrical nerve stimulation (TENS) for cancer-related pain and functionality

Records of patients who received TENS were reviewed for data collection. High-frequency TENS was trialed. Patients who reported subjective pain relief were provided with a TENS unit and instructed to use it four to six times daily for 30–60 minutes. Prior to the trial, pain was assessed. Pain was reassessed between one and two months.

• N = 55
• AGE RANGE = 10–89 years
• MALES: 22%, FEMALES: 78%
• KEY DISEASE CHARACTERISTICS: Varied tumor types

• SITE: Single site  
• SETTING TYPE: Outpatient  
• LOCATION: New York, NY

• APPLICATIONS: Palliative care

Retrospective, descriptive study

• Visual Analogue Scale (VAS)
• Numeric Rating Scale (NRS)
• McGill Pain Questionnaire Short Form (MPQ-SF)

Overall, 69.7% of patients who trialed TENS reported benefits. Among those who responded to TENS (40 patients), there was an average VAS score decrease of 9.8 mm (p < 0.001).

TENS may be helpful for pain management in patients with cancer. The results from this study were inconclusive.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Unintended interventions or applicable interventions not described that would influence results
• Measurement/methods not well described
• Other limitations/explanation: No information about whether analgesics were used or changed over time was provided. The results reporting was confusing, and the sample sizes reported in various places differed.

This study's findings regarding the efficacy of TENS for cancer-related pain treatment were not conclusive. Well-designed research evaluating its efficacy is needed so that options for improved pain management can be identified. Modalities such as TENS may be helpful adjuncts for patients who experience limited effectiveness with standard analgesics. However, good supporting evidence is needed.

To assess data to determine the effect of abiraterone acetate on pain and skeletal events in patients with castration-resistant prostate cancer

Patients were randomized to receive either 1 g abiraterone acetate or placebo orally once a day, along with 5 mg prednisone twice daily for 28-day cycles. Concomitant bisphosphonates were allowed during the study, if patients were already taking them or if a skeletal event indicated their use. Assessments occurred at baseline, on day 15, and on day 1 of the first 28-day cycle and during each subsequent 28-day cycle until the end of the study or treatment discontinuation.

• The sample was composed of 1,195 patients.
• Mean patient age was 69 years. Age range was 39–95 years.
• All the patients in the sample were male.
• All patients had castration-resistant prostate cancer. Overall, 43% of patients were using bisphosphonates and 89.4% had bone metastases.

• Multisite
• Outpatient
• Multiple countries

• Phases of care: late effects and survivorship
• Clinical application: palliative care

Randomized double-blind, placebo-controlled trial

Brief Pain Inventory

• Compared to patients taking placebo, a significantly larger proportion of patients receiving abiraterone acetate (p < 0.005) reported palliation of pain and pain interference.
• Median duration of pain palliation, 4.2 months, was longer in the abiraterone group (p = 0.0056).
• The proportion of patients to experience skeletal events was similar in both groups.
• Time to skeletal events was longer for patients taking abiraterone acetate (p = 0.0001).
• Both groups showed decline in pain intensity and interference over time.
• Median follow-up period for varied outcomes was 1–9.3 months. Follow-up survival curve analysis outcomes were better for those receiving abiraterone (p = 0.05).

Compared to placebo, abiraterone acetate and prednisone were associated with favorable effects on pain and a longer time to skeletal events in patients with metastatic castration-resistant prostate cancer.

• The findings of this analysis are not generalizable.
• The study was not stratified by use or nonuse of bisphosphonates.
• Authors provided very limited information and analysis regarding analgesic use and changes in analgesic use over the course of the study.

Findings show that prednisone and abiraterone acetate appeared to improve pain control in patients with castration-resistant prostate cancer. Chronic bone-related pain can be a severe problem for late-stage patients with prostate cancer. For these patients, abiraterone acetate and prednisone can be helpful in reducing pain and delaying skeletal events.

To evaluate the effectiveness of thee Tracheostomy Care Anxiety Relief through Education and Support (T-CARES) educational program for decreasing caregiver anxiety and increasing caregiver competence with tracheostomy suctioning

T-CARES is a one-hour course for caregivers about caring for a tracheostomy. The course is offered once a week in the hospital unit in a group setting. It involves an 18-minute video, group discussion, hands-on practice, and a return demonstration of tracheostomy care. The course covers the following topics: the introduction to airway anatomy, components of a tracheostomy tube, tracheostomy suctioning, stoma care, changing the ties securing the tracheostomy, cleaning the inner cannula, preparing for the unexpected, reinsertion of the tracheostomy tube after accidental decannulation, how to handle a mucous plug, when to call the doctor, and self-care. Evaluations were done at baseline and postintervention.

• N = 11  
• MEDIAN AGE = 50. 8 years (range = 31–69 years)
• MALES: 64%, FEMALES: 36%
• KEY DISEASE CHARACTERISTICS: Caregivers of patients with head and neck cancer with new tracheostomies
• OTHER KEY SAMPLE CHARACTERISTICS: 90% Caucasian; 81% had a high school education or above; and 90% had no prior tracheostomy experience

• SITE: Single site    
• SETTING TYPE: Inpatient  
• LOCATION: Central Florida

• PHASE OF CARE: Multiple phases of care

Nonexperimental, self-selected to receive the intervention pre- and post-test pilot study

• State-Trait Anxiety Inventory (STAI)
• Suctioning competency checklist
• Course evaluation

Mean STAI scores dropped from 50.5 to 34.3 after the intervention (p = 0.008). All participants were able to perform nine of the 14 skills needed for tracheostomy suctioning. Course evaluations were positive.

T-CARES is an effective intervention for reducing caregiver anxiety and increasing caregiver competency of tracheostomy care.

• Small sample (< 30)
• Risk of bias (no control group)
• Risk of bias (no blinding) 
• Risk of bias (no random assignment) 
• Risk of bias (no appropriate attentional control condition)  
• Risk of bias (sample characteristics)
• Questionable protocol fidelity
• Other limitations/explanation: No mention of how these registered nurses and trainers were calibrated as trainers although the protocol was standardized in its content and delivery; no mention of how the registered nurses and trainers who helped caregivers learn were trained in a standardized way themselves

Nurse-developed caregiver educational programs may be useful in decreasing anxiety and increasing competency for the development of new caregiver skills required for quality patient care. Additional research in this area is indicated.

To compare and evaluate the efficacy, safety, acceptance, and one-year outcome of two laxatives, polyethylene glycol (PEG) without electrolytes and milk of magnesia (MOM).

Patients were randomly assigned to intervention with PEG 3350 without electrolytes (Miralax^®) or MOM by drawing a sealed envelope. Patients initially received 0.7 g/kg of PEG or 2 ml/kg of MOM daily.

• A total of 117 children were asked to participate; 79 were enrolled and randomized.
• The PEG group comprised 39 patients (31 boys and 8 girls), whereas the MOM group comprised 40 patients (34 boys and 6 girls).
• Patients were included in the study if they were new referrals (more than one per week), were aged four years or older, and had presence of functional constipation with fecal incontinence.
• Patients were excluded if they had stool toileting refusal, fecal incontinence without constipation, previously refused one of the study medications, Hirschsprung disease, previous surgery involving the colon, chronic intestinal pseudo-obstruction, or come for a second opinion.

Children’s Hospital of Iowa

Randomized controlled trial

• Improvement was defined as three or more bowel movements (BMs) per week and two or fewer episodes of fecal incontinence per month with no abdominal pain, with or without laxative.
• Recovery was defined as three or more BMs per week and two or fewer episodes of fecal incontinence per month with no abdominal pain, without laxative treament for at least one month.
• Children who received additional senna were counted as not improved or recovered.

• Baseline characteristics were not significant (p > 0.07).
• Compliance rates were significant at 95% for the PEG group and 65% for the MOM group.
• After 12 months, 62% of the PEG group and 43% of the MOM group exhibited improvement and 33% of the PEG group and 23% of the MOM group recovered (not significant).

PEG and MOM are effective and safe in long-term treatment, with PEG having better acceptance.

• The study had a high drop-out rate (loss to follow-up).
• The study did not measure biochemical profiles for all children.

Placebo versus two treatment arms of recombinant coagulation factor VIIa: 20 mcg/kg and 80 mcg/kg

• N = 204
• OTHER KEY SAMPLE CHARACTERISTICS: Noncirrhotic adults undergoing partial hepatectomy for cancer and/or benign tumors

• Placebo-controlled RCT

• Designed for 50% relative reduction
• Outcome measures included erythrocyte transfusion during or 48 hours after surgery
• Amount of erythrocytes transfused
• Change in hematocrit
• Requirement of fresh frozen plasma
• Surgery time
   

Perioperative transfusion difference approached significance (P = 0.09). Mean requirements decreased with rFVIIa (P = 0.78). Blood loss during surgery decreased (P = 0.07).





 

• 80% power
• Significance level 5%
• Exceeded 180 sample size
• No statistically significant results
• Larger trial needed for better evaluation

A larger trial is needed for better evaluation.