To assess the effects of same-day pegfilgrastim administration compared to standard delayed administration among women being treated for gynecologic cancer

Medical records were used for data collection. Women received 6 mg pegfilgrastim on the same day as chemotherapy or within 24–72 hours of chemotherapy administration. Results of absolute neutrophil count (ANC), chemotherapy delay, regimen change related to neutropenia, and incidence of febrile neutropenia (FN) were compared. A 25% difference in risk of these outcomes was established as the noninferiority margin of interest. Sixty-one patients crossed over to the alternate timing of pegfilgrastim during treatment.

• N = 421   
• MEAN AGE = 59.4 years (SD = 12.1)
• FEMALES: 100%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Seventy-nine percent had ovarian cancer. The majority had stage III or IV disease.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: United States

• PHASE OF CARE: Active antitumor treatment

• Retrospective cohort comparison, noninferiority

• FN was ANC < 1000/mcl and a single temperature of 101 or sustained temperature of at least 100.4 for over one hour

Grade 3 or 4 neutropenia was observed more often in the same-day administration group (2.6% versus 1.8%, risk ratio [RR] = 1.62, p = 0.05). No significant differences in treatment delays or dose modifications existed within the established margin.

Same-day pegfilgrastim administration was associated with slightly higher grade 3 or 4 neutropenia.

• Baseline sample/group differences of import
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Key sample group differences that could influence results
• Much smaller number of patients who received same-day pegfilgrastim

This study did not provide sufficient evidence to establish safety and effectiveness of same-day pegfilgrastim administration. The findings suggest that altered timing may be safe in terms of looking at treatment delays related to neutropenia. Prospective studies are needed to determine whether same-day administration is appropriate. This approach can be very helpful for patients who need to travel long distances for treatment and may reduce the number of visits required for treatment.

In this prospective trial, patients were randomly assigned to one of two groups. Patients in the intervention group received five massage sessions (effleurage), lasting about 20 minutes. Patients in the control group received visits by a hospital staff member (attention control).

• The study consisted of 39 patients with breast cancer who were enrolled prior to the start of their third cycles of chemotherapy.
• The intervention group had 19 patients and the control group had 20 patients.

This was a prospective trial with random assignment.

• Patients completed a 100-mm visual analog scale (VAS) for nausea and anxiety before and immediately after the massage intervention or after the staff visit for the control group.
• The Hospital Anxiety and Depression (HAD) Scale was completed before the first and last massage sessions.

• No differences were found in anxiety as measured by the VAS between the groups.
• No differences were found between groups or within groups over time in anxiety or depression as measured by the HAD.
• The authors stated that nausea was significantly reduced in the massage group, as measured by the VAS; they did not report raw scores but, rather, “percentage improved.”

Interpretation of the findings as written was difficult. Although the authors concluded that massage reduced nausea, nausea was not assessed at expected problem points. For example, severe nausea was measured 30 minutes into the chemotherapy infusion after patients received antiemetic prophylaxis with 5-HT₃ and steroid.

• The hospital staff (nurses and nurses' aides) delivered the massage intervention after one day of training.
• No control was provided for consistency or adequacy of the intervention.
• Only nausea was assessed, not vomiting.
• Nausea was assessed by VAS immediately before and after the massage, but the massage was delivered during the chemotherapy infusion and nausea measured right after.
• The measurement period did not coincide with when nausea is expected to occur or be most severe. For example, nausea was measured prior to the start of massage, but nausea would not be expected to be present or severe at this time.

The study assessed the efficacy and the tolerability of gabapentin 900 mg/day compared to vitamin E for the control of vasomotor symptoms in women with breast cancer.

Vitamin E was chosen as a placebo-equivalent on the basis of previous experience  showing only minimal effect on hot flushes in breast cancer participants, and no toxicity or side-effects. Participants were randomly allocated to one of two treatment groups: vitamin E 800 IU/day or gabapentin 900 mg/day by oral route (Neurontin 300 mg capsules) for a period of 12 weeks.

The sample was comprised of 115 postmenopausal women with a median age of 50 years. 

• Inclusion criteria:
  • Breast cancer surgically treated at least one year prior; no evidence of systemic disease 
  • Eight or more hot flushes per day 
  • Postmenopausal status (amenorrhea for more than 12 months or amenorrhea for 6–12 months with a serum FSH level greater than 40 mIU/ml and estradiol less than 20 pg/ml or bilateral oophorectomy or ovarian suppression by GnRH analogs) 
  • Adjuvant therapy with tamoxifen, aromatase inhibitors or GnRH analogs, provided that it was started at least two months before
• Exclusion criteria:
  • Use of any antidepressant treatment, progestagens, or any other medication to treat hot flushes within the previous three months 
  • Concomitant chemotherap
  •  Uncontrolled hypertension 
  • Impaired renal or hepatic function
  • Diabetes

This was a randomized, non-placebo-controlled, nonblinded study.

Each participant completed a one-week self-report diary on hot flushes at study entry and daily during the 12 weeks of study. In order to assess the duration of treatment efficacy, participants filled out the hot flush diary for three months after treatment discontinuation.

Treatment efficacy was assessed by two measures: frequency (total number of hot flushes) and severity score, calculated by assigning scores of 1, 2, 3 and 4, respectively, to mild, moderate, severe, and very severe hot flushes. This hot flush diary had previously been validated. Each value was obtained by averaging data collected over 1 week. Differences and percentage changes from baseline to weeks 4, 8, and 12 were calculated. Among the women allocated to vitamin E, 16.36% never started therapy, and 34.78% dropped out because of inefficacy. Hot flush frequency and score decreased by 57.05% and 66.87%, respectively (p = 50.05) in the gabapentin group. The effect of vitamin E was fairly small: hot flush frequency and severity score were reduced by 10.02% and 7.28%, respectively (p > 0.05).

Gabapentin 900 mg/day is effective for relieving hot flushes in participants previously treated for breast cancer. Vitamin E has only marginal effect on vasomotor symptoms.

Study limitations were small sample size and high dropout rate.

• Evaluation of low-dose venlafaxine hydrochloride for the therapy of hot flashes in breast cancer survivors
• Evaluate the efficacy and tolerability of a longer treatment (eight weeks) at a lower dose of venlafaxine (37.5 mg/day)

• N = 40
• Patients attending the outpatient clinic for menopausal symptoms 
• All witha history of breast cancer without evidence of recurrence and no requirement of fulfilling menopausal status
• Anti-estrogen therapy was allowed provided that it had been started at least four months before study entry and continued the next three months

Outpatient

Open label study

Measures included:

• Hot flash diary and computation of daily hot flash scores
• Weekly documentation in diariesof side effects experienced  
• Beck Depression Inventory (BDI) as completed at baseline and at week 8 
• At weeks 4 and 8,a clinical visit to monitor blood pressure, assess side effects, and hot flash frequency
  • Patient was excluded from study if blood pressure found diastolic above 95 or systolic above 160, or if important side effect occurred

Thirty patients completed the first 4 weeks of treatment with reduction of hot flash frequency of 39% compared to baseline. After eight weeks of treatment, a further significant reduction in hot flashes by 53% and a hot flash score by 59% was observed. Very few side effects were reported, mainly nausea during first the two weeks and mouth dryness. Only 23 women completed the BDI at week 8 with a reduction of 23% reported. No patient was withdrawn for blood pressure increase or major toxicity.

Low-dose venlafaxine hydrochloride can be effective in reducing frequency and severity of hot flashes in patients with breast cancer.

• Not blinded or placebo-controlled  

The sudy evaluated the efficacy and safety of mirtazapine to reduce hot flashes in women with a previous breast cancer and assessed the influence of the same treatment on sleep quality and other menopausal symptoms.

Treatment was mirtazapine 15 mg/day at bedtime for one week, then 30 mg/day for the next 11 weeks. Primary end point was to compare hot flash score and frequency after 4, 8, and 12 weeks of treatment to the basal values.

The study enrolled 40 consecutive postmenopausal women with a previous history of breast cancer.

It was conducted in an outpatient treatment clinic for menopausal symptoms.

This was a pilot, open-label study.

Sample size was calculated under the assumptions of the detection of a 50% reduction in hot flash frequency, with 80% power at a two-sided alpha level of 0.05. These assumptions, using a dependant samples t-test, required at least 20 evaluable patients. Tools included: Hot flash diary, hot flash score, MRS, PSQI, and the SF 36 Health Survey.

Twenty patients completed the study. After four weeks of treatment, a significant decrease of vasomotor symptoms compared to baseline values was reported. The mean decrease in hot flash frequency was 46.9% and mean reduction in hot flash score was 49%. The benefit increased at week 8 when the mean decreases in frequency and score were 56.5% and 62.16% respectively. The effects remained stable during the last month.

The study was limited by its small sample size. Out of 40 women enrolled in the study 13 (32.5%) withdrew after signing consent and recording basal data and never began therapy;  reasons given for withdrawal included were reluctance to take antidepressant drugs or the fear that thedrug may adversely affect cognitive function or cause side effects.

The study should be duplicated in a larger blinded, placebo-controlled trial. There was a possible negative interaction between the antiproliferative effect of tamoxifen on the breast and mirtazapine.

• Assess efficacy and tolerability of gabapentin 900 mg/day compared to vitamin E for the control of vasomotor symptoms.
• Secondary objective to evaluate effect of the treatments on quality of sleep and other aspects of quality of life (QOL).

Patients were randomized to gabapentin 900 mg/day or vitamin E 800 IU/day for 12 weeks.

The study population included 115 adult postmenopausal women with history of breast cancer experiencing eight or more hot flushes per day. Sixty women completed the study. 

• Median age: 50 years
• Inclusion: Previous breast cancer surgically treated one year prior; no evidence of systemic disease; eight or more hot flushes per day; postmenopausal status; adjuvant tamoxifen, aromatase inhibitors or gonadotropin releasing hormone (GnRH) analogs allowed if started at least two months prior.
• Exclusion: Use of any antidepressant treatment, progestagens, or other medication to treat hot flashes within three months; concomitant chemotherapy; uncontrolled hypertension; impaired renal or hepatic function or diabetes.

Oncology Department University of Turin, Italy

Non–placebo-controlled, non-blinded trial

• Hot flush diary completed daily
• Pittsburgh Sleep Quality Index (PSQI)
• Menopause Rating Scale (MRS) 
• SF-36 Health Survey

Hot flush frequency and score decreased by 57.05% and 66.87%, respectively (p < 0.05) in the gabapentin group. Hot flush frequency and score were reduced by 10.02% and 7.28% respectively (p > 0.05) in the vitamin E group. Gabapentin improved the quality of sleep (PSQI score reduction: 21.33%, p < 0.05).

• Small sample size
• High dropout rate

To determine if ionic silver surgical dressings could reduce the incidence of surgical site infection in adult patients undergoing elective laparotomy for colorectal cancer

Subjects randomly were assigned to have their surgical wound covered with either an ionic silver dressing (AQUACEL^® Ag Hydrofiber^®) or a common dressing. To achieve blinding for patients, nurses, and medical staff, both groups had an additional layer of a common dressing applied by scrub nurses over the main dressing. Patients were monitored for surgical site infection for 30 days postoperatively.

• N = 112          
• AGE = 18–75 years (mean = 64 years)
• MALES: 58, FEMALES: 42
• KEY DISEASE CHARACTERISTICS: Elective laparotomy surgery for colorectal cancer

• SITE: Multi-site    
• SETTING TYPE: Inpatient    
• LOCATION: Italy

• PHASE OF CARE: Active antitumor treatment

• Randomized, prospective trial (double-blinded)

• Surgical site and vital signs evaluated daily during hospitalization, upon discharge, and at 30-day follow-up (surgical wounds remained covered for seven days)

The authors evaluated the primary outcome of surgical wound infection. Patient characteristics were similar across the two study arms. Surgical wound infection rates were lower in the arm receiving the antimicrobial dressing. This was true with respect to grade 1 versus grade 2 and 3, and grade 1 and 2 versus grade 3. However, the difference in infection rates was not great enough to be of statistical significance (p = 0.623).

Infection rates were slightly lower in the experimental group, but not enough to be statistically significant.

• The cover dressing purportedly provided blinding, but blinding would have been removed when the surgical dressing was removed. The article does not state whether surgeons or nurses were present when dressings were removed.
• Using the second layer of a common dressing over the antimicrobial dressing may have affected its performance, or may have affected the performance of the first layer of the common dressing in those patients randomized to the arm that received a double layer of the common dressing.
• The presence and severity of necrosis, erythema, edema, rigors, and hematoma are subjective analyses.

Patients having rectal surgery for cancer are at higher risk for surgical wound infection compared to colon surgery. Novel antimicrobial dressings may help reduce infection rates, but further study is needed.

To compare the effects of chlorhexidine-containing dressings and nonchlorhexidine dressing on catheter-related infections (CRIs) in neutropenic patients

Patients were randomized to receive either a transparent central venous catheter (CVC) dressing with a chlorhexidine gel pad or the transparent dressing without the gel pad. All catheters were nontunneled and placed in the subclavian or internal jugular vein with strict aseptic technique. Dressings were changed every 3–4 days. In the case of neutropenic fever, blood cultures were drawn, and if central line–associated bloodstream infections (CLABSI) were suspected, the catheter was removed and the tip was sent for culture. Patients were followed for 14 days.

• N = 613   
• MEAN AGE = 58 years
• AGE RANGE = 18–85 years
• MALES: 57.3%, FEMALES: 52.7%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: All were expected to have neutropenia for at least five days and expected CVC use of at least 10 days. All had hematologic malignancies. About half were undergoing autologous hematopoietic cell transplanation (HCT).
• OTHER KEY SAMPLE CHARACTERISTICS: Over 90% were receiving antimicrobials.

• SITE: Multi-site   
• SETTING TYPE: Inpatient    
• LOCATION: Germany

PHASE OF CARE: Active antitumor treatment

• Randomized, open-label

• Definite or probable catheter colonization—definite CLABSI was the primary endpoint
• Catheter-related sepsis

The study was discontinued early because the interim analysis did not show a significant difference in the primary endpoint of the study (definitive CLABSI) and further enrollment was not expected to make a difference. The incidence of probable bloodstream infection was less frequent in the study group (p = 0.014). No differences existed in sepsis, infection-related mortality. More unscheduled dressing changes occurred in the control group. Patients with coated CVCs had higher rates of catheter-related colonization and bloodstream infection (p = 0.007).

The use of a chlorhexidine gel pad CVC dressing was associated with a lower incidence of probable CLABSI but did not demonstrate a significant effect on definite catheter-related bloodstream infection within 14 days of CVC placement.

• Risk of bias (no blinding)
• Key sample group differences that could influence results 
• Measurement/methods not well described
• The study was underpowered.
• No complete subgroup analysis based on use of coated catheters
• The definition of probable and definitive infection was not well described.

Although this study did not show an effect of chlorhexidine gel pad CVC dressings on definitive CLABSI within 14 days, the gel pad dressing was associated with a lower incidence of probable catheter-related infection. This study had a large sample but was underpowered because of an overall low incidence of definitive CLABSI. The findings suggest that the use of a dressing with a chlorhexidine pad may be beneficial in reducing catheter-related infections.

To question: (a) Does aerobic or resistance exercise lead to lymphedema in women who are at risk? and (b) Does aerobic or resistance exercise reduce or exacerbate preexisting lymphedema?

Databases searched were in CINAHL, EMBASE ,MEDLINE PEDro, and PubMed.

Eight studies were reviewed; five were Sackett level V and three studies were level ll.

It has long been believed that aerobic exercise and UE resistance should be avoided for women at risk of or who have lymphedema; however, recent studies suggest that it may be safe.

Additional research with larger randomized controls is needed to determine the safety and effectiveness of exercise for women with breast cancer-related lymphedema.

Oral acetyl L-carnitine (ALC) was given at 1 g three times per day for eight weeks.

• The total samples consisted of 25 patients (3 men and 22 women) with a mean age of 53 years.
• The patients had grade 3 or greater neuropathy (based on the National Cancer Institute's Common Terminology Criteria for Adverse Events [NCI-CTCAE]) during paclitaxel or cisplatin therapy or grade 2 or greater persistent neuropathy after three months of therapy discontinuance.
• Exclusion criteria included having diabetes mellitus and neuropathy from origins other than paclitaxel or cisplatin.

The study had a non-randomized clinical trial design.

• Physical and neurologic examinations were conducted before and after ALC administration by an independent neurologist using the NCI-CTCAE grading scale.
• Conduction velocity of sensory and motor fibers was measured by electromyography.
• Neuropathy was measured by the Total Neuropathy Score (TNS), with each variable scored on a scale of 0 (none) to 4 (severe), and the sum of these forms the TNS.
• For a general neurologic evaluation, patients were evaluated for bulbar symptoms of muscle weakness sensory disturbances (negative, positive) and autonomic symptoms.

Twenty patients had neuropathy attributed to paclitaxel and five from cisplatin. Six of the 25 were receiving a taxane at enrollment; the remaining 18 patients has persistent neuropathy at enrollment. Sensory neuropathy improved in 15 patients and motor neuropathy improved in 11. In addition, sensory and motor action potentials (SNAP and CMAP) improved significantly in 21 patients and CMAP improved in 12 patients (non-significant). Twenty-three patients had amelioration of the TNS score, and one patient (receiving concomitant vinorelbine) worsened. Patients showed improved bulbar and limb muscle weakness and sensory disturbance scores after eight weeks of ALC. No change in autonomic symptoms was observed. All patients had normalization of motor strength, deep tendon reflexes, and vibration.

• Limitations include a small sample size of 25 patients with differing levels of neuropathy and no statistical control for confounding variables.
• Although the researchers used comprehensive testing for neuropathy, the use of many variables of neuropathy that were assessed by statistical t tests is cause for concern related to galloping alpha effect, making obtaining statistical significance more likely.
• The one-group, non-randomized design and lack of a control group makes it impossible to infer causality. Testing for these patients (clinical, neurophysiological) is time consuming, painful (nerve conduction), and costly.