To compare the efficacy and safety of posaconazole and fluconazole in the prevention of invasive fungal infection (IFI) in Chinese patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) receiving chemotherapy

Patients in China with MDS or AML with persistent chemotherapy-induced neutropenia (expected to last longer than seven days) were enrolled. Posaconazole or fluconazole was administered for a maximum of 12 weeks, or until recovery from neutropenia and complete remission or until IFI was diagnosed. The endpoint was incidence of proven, probable, or possible IFI during treatment.

• N = 244  
• AGE = 18–70 years; median in posaconazole group was 40 years (range: 17–61 years), median in fluconazole was 40 years (range: 15–68 years)
• MALES: Posaconazole, 55%; fluconazole, 52%  
• FEMALES: Posaconazole, 62%; fluconazole, 65%
• KEY DISEASE CHARACTERISTICS: De novo AML (posaconazole, 56%; fluconazole, 60%; relapsed AML (posaconazole, 46%; fluconazole, 45%); MDS (posaconazole, 15%; fluconazole, 12%)
• OTHER KEY SAMPLE CHARACTERISTICS: Duration of neutropenia in posaconazole (less than two weeks, 52%; more than two weeks, 65%); in fluconazole (less than two weeks, 55%; more than two weeks, 62%)

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

• PHASE OF CARE: Active antitumor treatment

• Prospective, randomized study

• Fisher’s method was used for analyzing between-group comparison. 
• A Kaplan-Meier analysis was used to calculate time-related parameters, including the time to first onset of proven, probable, or possible IFI, and time to first use of empirical antifungal therapy (from day of randomization).
• Log-rank tests were used for comparison between groups.

Two hundred forty-five patients entered safety analysis (124 in posaconazole and 121 in fluconazole). After exclusions, 117 patients were included in each set. Incidence of IFI was 9.4% and 22.2% in the posaconazole and fluconazole groups, respectively. There was a difference in rates of -12.8% in favor of posaconazole. There was an incidence of 3.42% when only proven and probable diagnoses were considered. Noninferiority of posaconazole compared with fluconazole was established with a difference in incidence rate of -5.98%. The 100-day time to first onset of proven, probable, or possible IFI was 13.8 (SD = 3.5%) in the posaconazole group and 29.2 (SD = 4.6%) in the fluconazole/itraconazole group.

Antifungal prophylaxis has been shown to be a successful strategy in patients at high risk for IFI. Posaconazole showed significant advantage compared with fluconazole in reducing the incidence of IFI. The advantage of posaconazole in decreasing the incidence may translate into reduced need for systemic antifungal treatment.

The study raises awareness of the potential for use of posaconazole as a reasonable prophylactic medication for IFI. There is some evidence that second-generation azoles may be more effective for prophylaxis in high-risk patients.

To compare the effectiveness of electroacupuncture, minimal needling and mock electrical stimulation, or antiemetic medications alone in controlling emesis among patients undergoing highly emetogenic chemotherapy

Participants were randomly assigned to one of three groups.

• Low-frequency electroacupuncture at classic antiemetic acupuncture points once daily for five days
• Minimal needling at control points with mock electrostimulation once daily for five days
• No adjunct needling

• The study consisted of 104 patients.
• The mean age was 46 years with a range of 18–62 years.
• All participants were women with histologically proven resected breast cancer undergoing myeloablative chemotherapy, Karnofsky scores of 80 or more (on a 0–100 scale), and life expectancy of at least six months. All participants were appropriate candidates for bone marrow transplantation.
• Patients were excluded from the study if they had brain metastases, cardiac pacemakers, life-threatening concurrent nonmalignant conditions, or active skin infections over the proposed treatment area.

Participants were from an inpatient unit at a tertiary hospital with a comprehensive cancer center. Patients were recruited from oncology clinics.

The study design was random, without stratification.

Investigators recorded the total number of emetic episodes during the five-day study period and the proportion of emesis-free days across the treatment groups.

• The electroacupuncture group had significantly fewer emesis episodes than the minimal needling group or the pharmacotherapy group alone (p < 0.001).
• The minimal needling group had significantly fewer episodes of emesis than the pharmacotherapy group alone (p = 0.01).
• The electroacupuncture group had a greater proportion of emesis-free days than the other groups (p < 0.001).
• No significant difference existed between the groups over days 6–14.

• Homogeneity of sample (standard chemotherapy and supportive care) helped to increase the precision in measurement; however, generalizability is limited.
• The study did not include 5-HT₃ antagonists or corticosteroids.
• Training is required for electroacupuncture and minimal needling. The two investigators administered the procedure (training completed with 3–20 years of experience).
• Time commitment was 30 minutes a day for five days.
• This was a grant-funded project. 

• The beneficial effect of electroacupuncture may be related to attention and clinician-patient interaction.
• Minimal needling led to a reduction in emesis, which could have been a placebo effect.
• Electroacupuncture has been thought to modulate serotonin, substance P, and endogenous opioids (similar to drugs that are available now).

To examine the effects of electrostimulation at the K1 acupoint located on the sole of the foot on chemotherapy-induced nausea and vomiting (CINV)

After institutional review board approval, 103 patients with metastatic liver cancer undergoing transcatheter arterial infusions (TAIs) of cisplatin or oxaliplatin were recruited and randomized to group A (tropisetron and electroacustimulation at the K1 acupoint) or B (tropisetron and electrostimulation at a placebo point on the heel). The treatment in both groups lasted for 20 minutes one to two hours before TAI on day 1 and then daily (7 am–9 am) for the subsequent five days. The baseline rate, intensity, and duration of CINV were collected for five days after TAI. Quality of life was assessed daily.

• N = 103 (51 in group A and 52 in group B)
• MEAN AGE = 53.4 years (range = 20–73 years)
• MALES: 80 (77.7%), FEMALES: 23 (22.3%)
• KEY DISEASE CHARACTERISTICS: Liver cancer (primary and metastatic)
• OTHER KEY SAMPLE CHARACTERISTICS: Participants aged 18–75 years scheduled to receive cisplatin or oxaliplatin via TAI for the first time; negative pregnancy test for fertile female patients; no local skin infections near the acupoints; no cerebrovascular accidents; no intestinal obstructions; no vomiting or 5HT3 receptor antagonist or other antiemetic use within 24 hours before TAI; no cardiac pacemaker; not currently using acupuncture; and no mental incapacity or psychiatric disorder

• SITE: Single site    
• SETTING TYPE: Inpatient    
• LOCATION: Fudan University Shanghai Cancer Center in Shanghai, China

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

Double-blinded, randomized, placebo-controlled, longitudinal clinical trial

• Daily diaries recording episodes of emesis, the time when each episode occurred, the degree of emesis, and a rating for nausea duration and severity in the previous 24 hours
• Visual Analog Scale (VAS) on 0–10 scale used to record nausea intensity
• Medications record 
• Quality of life was assessed daily using the MD Anderson Symptom Inventory (MASI) and the EuroQoL scale (24 hours)

No differences were found between groups A and B in regard to the incidence and degree of nausea or vomiting at any time point. Patients in group A had better EuroQoL scores than patients in group B (72.83 versus 65.94, p = 5.04) on day 4 but not other days. No group differences were noted at any time point for MASI scores.

Noninvasive electrostimulation of the K1 point combined with tropisetron had no effect on cisplatin-induced or oxaliplatin-induced nausea or vomiting.

• Intervention expensive, impractical, or training needs
• Other limitations/explanation: Needed acupuncturist to locate the site of stimulation; did not follow antiemetic guidelines and did not give dexamethasone with tropisetron; gave extra antiemetics for patients who experienced CINV; opioid use was not assessed; and frequency of electrostimulation administration was not sufficient

Patients receiving chemotherapy experience CINV frequently with highly emetogenic regimens. Complementary therapies might be helpful in reducing this side effect. Instructing patients to refer to their physicians before trying a new intervention is advisable.

To explore the effects of acupressure on chemotherapy-induced nausea and vomiting (CINV)

A convenience sample of patients was recruited, and patients were randomized to receive acupressure on two sites on both sides of the body or acupoint patches on a single site on both sides of the body. All patients were receiving standard triplet antiemetics. Study data were collected prior to and after the acupressure intervention and 48 hours after chemotherapy. Study data were collected three times—before chemotherapy, before dinner on the day of chemotherapy, and before breakfast on the following day. The acupressure group had pressure applied to the PC6 and SP4 points on both sides of the body, for three minutes on each point.

• N = 70   
• MEAN AGE = 58.6 years (SD = 0.2)
• MALES: 61.4%, FEMALES: 29.6%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: All had lung cancer and were receiving cisplatin-based chemotherapy.

• SITE: Single site   
• SETTING TYPE: Not specified    
• LOCATION: Taiwan

PHASE OF CARE: Active antitumor treatment

Two group, randomized trial

• Morrow Assessment of Nausea and Emesis (MANE)
• Meridian Energy Analysis Device

The mean meridian energy was significantly higher in the group receiving acupressure after the intervention (p = 0.003) compared to those who had acupoint patches. Analysis showed an effect on study groups across all study measurement times, with lower nausea (p < 0.001) and vomiting (p = 0.023) severity in the acupressure group.

Acupressure on PC6 and SP4 acupoints prior to chemotherapy and meals was associated with a lower severity of nausea and vomiting.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Findings not generalizable

The use of acupressure as an adjunct to standard antiemetic treatment may reduce the severity of CINV in patients receiving emetogenic chemotherapy. Nausea is still not well controlled in most individuals with maximal antiemetic use. Acupressure is a low-risk intervention that may be helpful for CINV control, specifically nausea control.

To evaluate the effectiveness of educational interventions in reducing patients’ nausea expectations by dispelling misconceptions about chemotherapy-induced nausea and vomiting (CINV) and building confidence in antiemetic regimens

Patients were randomized one of two arms. Both arms received the same educational materials except that arm 2 patients received an additional handout emphasizing the benefits and effectiveness of ondansetron in the control of nausea and vomiting. Both arms received a standardized antiemetic regimen including ondansetron and dexamethasone on day one. Nausea and vomiting were measured in a patient-reported diary from day one to day four following chemotherapy treatment.

• The study consisted of 322 patients who were chemotherapy-naïve.
• The mean age in arm 1 (control group) was 57.8 years (SD = 13.4 years, n = 163). The mean age in arm 2 (intervention group) was 57.4 years (SD = 12.1 years, n = 59).
• The majority of the patients were female (73%).
• Diagnoses were not reported.
• In arm 1, 52.1% of patients were receiving adriamycin, 34.4% were receiving carboplatin, and 13.5% were receiving cisplatin. In arm 2, 52.8% of patients were receiving adriamycin, 31.4% were receiving carboplatin, and 15.7% were receiving cisplatin.

The study was conducted at 18 medical oncology practices (all Community Clinical Oncology Programs [CCOPs]) across the United States.

All patients were in active treatment.

This was a randomized, multicenter, clinical trial.

• Expectation of nausea was measured using a five-point Likert-type scale anchored at one end by “1” = I am certain I WILL NOT have nausea” and the other end “5” = I am certain I WILL have nausea.
• Patients measured nausea and emesis four times a day and recorded their experiences in report diaries.
• Assessments were documented from the treatment day until the fourth day following the chemotherapy treatment.
• Nausea severity was assessed on a 7-point rating scale.

• No significant difference was found between groups in frequency or severity of nausea.
• Approximately 76% reported no nausea, and approximately 25% experienced or average nausea.
• A significant reduction in nausea expectancy was seen in the intervention group as compared to the control group (p = 0.024).

Although the expectancy manipulation reduced patients’ reported expectations for the development of nausea, the occurrence of nausea was not reduced. Changing nausea expectancies did not affect the occurrence of nausea.

• The expectancy manipulation in this study may not have been strong enough. The educational intervention was a one-page handout with basic statements.
• Use of a reliability and validity expectancy measurement tool was not documented.
• Past experiences of nausea and vomiting (motion or morning sickness) or the influence of past exposures to family or friends undergoing chemotherapy, which may have influenced chemotherapy-related nausea, was not considered.

Educational interventions to increase awareness of nausea prior to first chemotherapy administration may reduce patients’ expectations for subsequent CINV. However, these interventions may not reduce actual nausea severity or occurrence.

To assess the efficacy of prophylactic benzydamine in an oral solution for reducing the signs and symptoms of oral mucositis in patients receiving radiation therapy (RT) with or without chemotherapy for head and neck cancers

A 0.15% benzydamine or placebo oral rinse of 15 ml was used for two minutes four to eight times daily starting the day before RT and continuing till two weeks RT completion.

• N = 51  
• MEAN AGE = 52.65 years
• MALES: 60.8%, FEMALES: 39.2%
• KEY DISEASE CHARACTERISTICS: Head and neck cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Adults receiving at least 5,000 cGy RT via megavoltage treatment with either cobalt 60 or a linear accelerator to at least two oral mucosal sites with a Karnofsky Performance Status (KPS) > 60

• SITE: Single site    
• SETTING TYPE: Not specified    
• LOCATION: Jorjani Cancer Center at the Shahid Beheshti University of Medical Sciences in Tehran, Iran (2009–2012)

• PHASE OF CARE: Active antitumor treatment

Randomized, double-blinded, placebo-controlled trial stratified according to KPS and treatment schedule (once- or twice-daily fraction) and then randomized

• The oral cavity was divided into 14 anatomical sites.  
• A complete oral examination was done weekly after the initiation of treatment, and a four-point scale was used to score each oral site.  
• At each weekly visit, an overall mean score was calculated based on at-risk areas.

No difference in the severity of mucositis was found during weeks 1–3. By week 4, the placebo arm had significantly more mucositis than the treatment arm (p = 0.01), and this trend continued until the end of treatment. The difference in the mean score at one and two weeks after treatment continued to show lower scores in the treatment group, but this was nonsignificant.

An oral rinse of benzydamine 0.15% was safe and well-tolerated with no noticeable side effects reported by patients. It reduced the incidence and severity of radiation-induced oral mucositis.

• Small sample (< 100)
• Risk of bias(sample characteristics)
• Unintended interventions or applicable interventions not described that would influence results
• Measurement validity/reliability questionable
• Other limitations/explanation: Single site; unable to analyze data regarding analgesic consumption because of noncompliance; unclear who did the oral examination and training to ensure interrater reliability

Benzydamine was well-tolerated, easy to administer, and may be an appropriate prophylactic treatment for oral mucositis in patients receiving RT for head and neck cancer.

To evaluate the safety and efficacy of single-dose palifermin in reducing oral mucositis incidence in patients with hematologic malignancies undergoing peripheral blood progenitor cell transplant receiving total-body irradiation and high-dose chemotherapy 

Patients were randomized to receive 60 mcg/kg palifermin once daily for three days before the start of fractionated total-body irradiation (TBI) (Arm A), 180 mcg/kg once only on day -1 (Arm B), day -2 (Arm C), or day -3 (Arm D) before starting fractionated TBI and stratified by etoposide use and number of days of TBI.  All patients received 60 mcg/kg for three days post-transplantation.

The study reported on 47 patients receiving high-dose chemotherapy with an age range of 18–74 years. Patients had multiple cancer diagnoses.

The World Health Organization (WHO) Oral Toxicity Scale was used.

• All arms had similar adverse effects.
• Overall incidence of severe mucositis was 61% with a mean of 4.3 days.
  • Arm A: 82% (70% actual)
  • Arm B: 60% (73% actual)
  • Arm C: 31% (38% actual)
  • Arm D: 75% (67% actual)

• The four study arm sample sizes were small.
• The total sample was small with only 47 patients total.
• The authors collapsed Arms B, C, and D for severe mucositis.
• A large percentage (n = 20) of patients had significant protocol deviations.
• The study was stopped early; participant accrual was difficult.
• The report did not include a discussion of costs.

To investigate the effect of 3M™ Cavilon™ No-Sting Barrier Film and topical corticosteroids on irradiated skin

Thirty-nine post-operative patients with breast cancer were assigned to the three intervention groups using simple randomization. The three treatment groups included 3M barrier film versus no treatment [n = 13], Elomet^® (mometasone furoate [corticosteroid] cream) versus no treatment [n = 9], and Elomet versus 3M barrier film [n = 17]. Each participant’s treatment field was divided in half so that she received both radiodermatitis treatments assigned to the group. Elomet and 3M film barrier were applied every other day, excluding weekends, by the same staff, and the reactions were observed. For patients with more advanced disease, chest wall recurrence, or lymph node involvement, those areas also were irradiated. The skin reactions in the neck and supraclavicular areas were not included in the study. The primary end points were time to onset of grade 1 pruritus, a pain score of 3, and presence of grade 2 dermatitis. The secondary end points were grade 3 radiodermatitis and pain scores by each treatment.

• N = 39  
• AGE = 30–76 years
• MEAN AGE = 51 years
• MALES: 0%, FEMALES: 39%
• KEY DISEASE CHARACTERISTICS: Breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Chest wall, remaining breast after conservative surgery, treated skin, untreated skin, post-operative

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

• PHASE OF CARE: Active antitumor treatment

Open-label clinical trial of barrier film or corticosteroid cream, versus no treatment to prevent/reduce grade 1 pruritus, grade 2–3 radiodermatitis, and pain score of 3.

• Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 for dermatitis associated with radiation and for pruritus
• A pain score was collected.
• SPSS software version 10 was used to analyze the data.

The authors recommend using the barrier film starting at the commencement of treatment to reduce friction and irritation, particularly in skin folds and the axilla. However, study findings here do not show an effect on development of radiodermatitis. Once pain and hyperemia occur, the barrier film is discontinued and corticosteroid cream started. The effectiveness of corticosteroid on prevention of radiodermatitis should be investigated further under a lager randomized study.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Key sample group differences that could influence results
• Measurement/methods not well described
• Intervention expensive, impractical, or training needs
• Other limitations/explanation:  The researchers said they used “simple randomization” to assign the participants to the three treatment groups. They did not explain what they meant by “simple randomization.” The number of participants in each treatment group differed. Demographics for the members of each treatment arm were not provided. Some participants were receiving first-line treatment for a new breast cancer. Others were experiencing a recurrence. Some participants had a modified radical mastectomy, and some had breast-conserving surgery. The authors did not report the use of a power analysis to determine the sample size required to accurately identify statistically significant differences between the treatments, nor the expected effect size of the intervention. It is unlikely that 13 participants in each treatment arm would provide enough power to detect significant differences. The participants in the 3M barrier film versus no treatment and the Elomet (mometasone furoate [steroid] cream) versus no treatment arms served as their own control. The participants in the Elomet versus 3M barrier film arm did not have a control. The volume and type of tissue in each half of the treatment field may not have been identical. The skin dose in each half may have differed and was not reported in this article. Inter-rater reliability was not reported. The method of measuring pain score was not reported.  A pain score of 3 was an endpoint, but the range was not identified.

The effectiveness of corticosteroids on prevention of radiodermatitis should be investigated further in a large, randomized, controlled clinical trial with adequate power to detect clinically significant differences and controlling for confounding factors.

To evaluate whether using dietary interventions could be beneficial in the treament of arm lymphedema in patients who have breast cancer-related lymphedema

• The study sample (N =64) was comprised of female patients.
• Patients were stratified by volume and treatment and then randomized to one of three groups.
  • Weight reduction with decreased calories to 1,000–1,200 a day
  • Low-fat diet without change in calories, reducing dietary fat to 20% of total calories
  • Control group without change from intake
• Fifty-one patients completed the study.

The study used a randomized controlled trial design with two interventions and one control group.

• The volume measurements were performed by lymphedema practitioners who were blinded to the intervention using a Perometer and a volume equation using circumference.
• Arm circumference was measured every 4 cm.
• Height and weight were measured.
• Skin fold thickness was measured at four sites.

Results showed significant reduction in body weight (p = 0.006), body mass index (p = 0.008), and skin fold thickness measured at four sites (p = 0.044) in the weight-reduction and low-fat groups but not in the control group. There was a reduction in excessive arm volume over the 24 weeks but no significant difference between groups. There was a significant correlation between weight loss and a reduction in excess am volume irrespective of the dietary group (p < 0.002). Weight loss for the control, weight-reduction, and low-fat groups were 60%, 95%, and 76%, respectively. Weight reduction appears to be an effective means of assisting in the reduction of arm volume during the treatment of the lymphedema arm.

A good study that identifies an important risk factor and intervention.

• The study was ambitious and could have benefited from a simple weight-controlled study.
• Patients used compression sleeves and bandages during the intervention; nevertheless, the patients were distributed throughout the groups.
• Patients had poor adherence to diets.
• Some patients who were instructed not to lose weight did.
• The calorie intake of 1,000–1,200 per day is low for anyone.

Participants initially were given donepezil 5 mg per day. After 6 weeks, dosage was increased to 10 mg per day for a total of 18 weeks. Treatment then was discontinued for a six-week washout period. Patients, therefore, served as their own control at two points (baseline and post-washout). After week 30, patients were given the choice to continue using donepezil at 10 mg per day. Patient outcomes were assessed at baseline and at week 6, 12, 24, and 30 (following the washout period).

• N = 35 enrolled (24 patients remained on the study and completed all assessments)
• MEDIAN AGE = 45 years
• KEY DISEASE CHARACTERISTICS: All had primary brain tumor, mostly low-grade glioma
• FEMALES: 46%
• OTHER KEY SAMPLE CHARACTERISTICS: 92% white, 8% black. Patients who remained on the study did not differ significantly at baseline from the patients who dropped out on the measures of sex, race, mood, and cancer-related quality of life. Patients remaining on the study were significantly younger than those who dropped out.
• EXCLUSION CRITERIA: Less than 18 years of age, life expectancy of less than 30 weeks, received partial or whole brain radiation less than six months before enrollment, imaging evidence of tumor progression in the previous three months, brain tumor treatment planned during course of study

• Wake Forest University School of Medicine in Winston-Salem, NC

• Active treatment

• Open-label, phase II clinical trial

• Profile of Mood States (POMS)

The donepezil intervention group demonstrated a significant improvement in fatigue from baseline to 24 months as shown by the POMS subscale for fatigue (p = 0.03).

• Lack of a neutral comparison group
• Possible that observed improvement is result of “practice effect,” as participants were required to fill out forms four times over a 7.5-month time period