To compare antibiotic prophylaxis with placebo or no intervention or another antibiotic in patients with afebrile neutropenia

DATABASES USED: Cochrane Cancer Network Register of Trials (December 2004), Cochrane Library (Issue 4, 2004), EMBASE (January 1980–December 2004), and MEDLINE (January 1966–December 2004); the reference lists of all the articles also were searched.

FINAL NUMBER STUDIES INCLUDED = 95 RCTs

TOTAL PATIENTS INCLUDED IN REVIEW = 9,283 patients comparing prophylactic antibiotics with placebo, no intervention, or other prophylactic antibiotics

KEY SAMPLE CHARACTERISTICS: Sixty-four trials included only patients with hematologic malignancies, and nine trials consisted of more than 80% of patients with solid tumors. Twenty-seven studies included patients undergoing bone marrow transplantation (BMT).

Prophylactic antibiotics significantly decreased

• Overall mortality by 33% (although the effect was less robust in the well-designed trials)
• The risk of infection-related death by 42%
• Fever by 21%
• Clinically documented infections by 36%
• Microbiologically documented infections by 46%
• Gram-negative infections by 61%
• Gram-positive infections by 58%
• Bacteremia by 48%.

Fluoroquinolones, when compared with placebo or no intervention, decreased the risk of

• Overall mortality compared with placebo or no intervention by 48%
• Infection-related mortality by 62%
• Clinically documented infections by 47%
• Microbiologically documented infections by 50%
• Gram-negative infections by 74%
• Gram-positive infections by 71%
• Bacteremia by 36%.

The relative risk for adverse events was not statistically significant (relative risk 1.30 [confidence interval 0.61–2.76]). Comparatively, in trials comparing trimethoprim/sulfamethoxazole with placebo or no intervention, the corresponding estimates were statistically significant (relative risk 2.42 [confidence interval 1.35–4.36] and 3.63 [confidence interval 1.32–9.98], respectively). Moreover, in trials that compared fluoroquinolones with trimethoprim/sulfamethoxazole, less resistance developed to fluoroquinolones in the fluoroquinolone group than that developed to trimethoprim/sulfamethoxazole in the trimethoprim/sulfamethoxazole group (relative risk 0.45 [confidence interval 0.27–0.74]). When fluoroquinolones were compared with placebo, the number of fungal infection episodes did not statistically or significantly differ (relative risk 0.83 [confidence interval 0.56–1.22]).

Fluoroquinolone prophylaxis increased the risk of fluoroquinolone-resistant infections, but the increased risk was not statistically significant (relative risk 1.69 [confidence interval 0.73–3.92]).

The purpose of this meta analysis and sytematic review was to evaluate the effect of antibiotic prophylaxis on mortality and infection in neutropenic patients. In addition, subgroups of patients who may benefit the most were identified, and whether or not the effectiveness of different antibiotic regimens were similar was evaluated, as were the adverse effects of different regimens and the emergence of quinolone-resistant bacteria.

• Databases searched from 1996–2011 included MEDLINE, EMBASE, Cochrane databases of controlled trials and cancer network registry of trials, multiple relevant conference proceedings.
• Regarding keywords, appendices provided extensive detail of exact search terms used per database.
• Inclusion criteria included patients with cancer and neutropenia from chemotherapy or after bone marrow transplantation. Control groups received placebo, no intervention or an alternate intervention, quasi-randomized controlled trials, or randomized clinical trials (RCTs) for initial review through 2005. An update to 2011 included only RCTs. Exclusion criteria were not stated,.

119 total references were retrieved. Cochrane Handbook for Systematic Reviews methods were used to evaluate and commend on the literature used.

• 109 total studies were evaluated.
• 13,579 cases were reviewed.
• Key characteristics: patients with cancer—sites not specified—but most involved patients with leukemia. Some studies sampled febrile episodes rather than cases.

Active antitumor treatment

Antibiotic prophylaxis resulted in significant reduction in risk of mortality across 46 trials analyzed (RR = 0.66, 95% confidence interval [CI] [0.55, 0.79], p < 0.00001). The greatest effect was with quinolones, although differences between regimens was not statistically significant. The effect was larger for trials in which prophylaxis was begun at the onset of neutropenia. An advantage was seen for all quinolones except for norfloxacin. Antibiotic prophylaxis significantly reduced infection-related mortality (RR = 0.61, 95% CI [0.48, 0.77], p = 0.04), decreased occurrence of fever, documented infection, and occurrence of bacteremia. Quinolones and TMP-SMZ were both associated with side effects that were mostly diarrhea and nausea. TMP-SMZ was associated with drug resistant bacteria cultures (RR = 2.42, 95% CI [1.35, 4.36]).  With quinolones, no significant differences were noted between study groups compared to placebo or other interventions. Addition of gram-positive coverage did not show any apparent benefits in terms of mortality.

Findings support use of quinolones as prophylaxis of choice since they reduced risk of death compared to placebo or not intervention and were generally associated with fewer side effects and less resistant bacterial cultures in treated patients. Levofloxacin or ciprofloxacin are recommended.

• All cause mortality was only available for 47 of the studies. 
• Length of follow-up in studies may have been too short to fully detect emergence of resistant bacteria. 
• Most studies were limited to patients with hematologic cancers. 
• Applicability to patients with solid tumor types requires further study.

Prophylactic quinolone antibiotic therapy is recommended for patients with hematologic cancers and those who are likely to develop neutropenia. Additional research is needed to better define patients with solid tumors that may benefit from antibiotic prophylaxis. In most studies, prophylaxis was begun when chemotherapy was initiated, rather than when neutropenia occurred.  Prophylaxis should be accompanied by surveillance to monitor quinolone-resistant gram-negative bacteria and other resistant organisms.

To compare antibiotic prophylaxis with placebo, no intervention, or another antibiotic to prevent bacterial infections in patients with afebrile neutropenia

DATABASES USED: Electronic searches on the Cochrane Cancer Network Register of Trials (2005), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2005), MEDLINE (1966–2005), EMBASE (1980–2005), and abstracts of conference proceedings; references of identified studies; the first author of each included trial was contacted.

FINAL NUMBER STUDIES INCLUDED = 101

TOTAL PATIENTS INCLUDED IN REVIEW: 12,599

KEY SAMPLE CHARACTERISTICS: RCTs or quasi-RCTs performed from 1973–2005; patients with cancer and neutropenia as a result of chemotherapy or bone marrow transplantation

Antibiotic prophylaxis significantly decreased the risk of death when compared with placebo or no intervention (RR 0.66 [95%CI 0.55 to 0.79]). The authors estimated the number needed to treat in order to prevent one death from all causes as 50 (95% CI 34 to 268). Prophylaxis with any antibiotic resulted in a significant decrease in the risk of infection-related death (RR 0.59 [95% CI 0.47 to 0.75]) and in the occurrence of fever (RR 0.77 [95% CI 0.74 to 0.81]). Quinolone prophylaxis reduced the risk for all-cause mortality (RR 0.52 [95% CI, 0.37 to 0.74] and the risk of infection-related mortality (RR 0.49 [95% CI 0.31 to 0.77]). 

Antibiotic prophylaxis resulted in a significant decrease in the occurrence of clinically documented infection (RR 0.66 [95% CI 0.61 to 0.73]), microbiologically documented infection (RR 0.53 [95% CI 0.48 to 0.58]), microbiologically documented gram-negative infection (RR 0.38 [95% CI 0.32 to 0.45]), microbiologically documented gram-positive infection (RR 0.44 [95% CI 0.38 to 0.51]), and bacteremia (RR 0.52 [95% CI 0.47 to 0.59]. Quinolone prophylaxis reduced the risk of bacteremia (RR 0.58 [95% CI 0.50 to 0.68]. When compared to placebo or no intervention, all prophylactic antibiotics caused more side effects (RR 1.59 [95% CI 1.37 to 1.85]. There was no statistically significant difference in the number of episodes of fungal infection when prophylactic antibiotics were compared to placebo (RR 1.07 [95% CI 0.83 to 1.37, 38 studies, 2,682 participants]).

When compared to placebo, patients given quinolones and sulfamethoxazole/trimethoprim (SMZ-TMP) were found to be at increased risk of harboring bacilli resistant to the specific drug than patients receiving placebo (RR 1.47 [95% CI 1.08 to 2.01]). For quinolones, the RR was 1.18 (95% CI 0.81 to 1.70) and for SMZ-TMP, 2.42 (95% CI 1.35 to 4.36). When quinolones were compared to SMZ-TMP, the following were significantly reduced: microbiologically documented infections (RR 0.72 [95%CI 0.6 to 0.86]) (comparison 5.2), gram-negative infections (RR 0.21 [95% CI 0.13 to 0.36]) (comparison 6.2), gram-negative bacteremia (RR 0.35 [95% CI 0.21 to 0.59]), and side effects (RR 0.74 [95%CI 0.63 to 0.87]). The addition of antibiotic against gram-positive infection to quinolones resulted in a significant decrease in the number of bacteremic episodes (RR 0.72 [95%CI 0.57 to 0.92], gram-positive infections (RR 0.49 [95% CI 0.37 to 0.64], and gram-positive bacteremia (RR 0.61 [95% CI 0.45 to 0.83]), and also in more side effects.

• Most studies were limited to patients with hematologic cancer (mostly leukemia).
• Most were conducted on hospitalized patients.
• Information on all-cause mortality could not be obtained for all of the studies.
• Many studies were dated.

Acupuncture-like transelectrical nerve stimulation (AL-TENS) with low-frequency, high-intensity stimulation using acupuncture points for emesis and analgesia was delivered by a nurse practitioner in five consecutive daily treatments. The study was divided into three groups:  AL-TENS, standard care, and standard care plus placebo.

• The study included 15 adults with multiple cancer diagnoses admitted for symptom control for pain or nausea and vomiting.
• Complete data were collected for 13 participants.
• Age ranged from 38 to 74 years.
• Of the participants, 14 were female, all were Caucasian, and three were in the end-of-life phase of care.

• Hospice
• United Kingdom

The study was a pilot study and a double-blind, randomized, controlled trial.

• European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) fatigue subscale at baseline and day six (posttreatment)
• Pain
• Nausea and vomiting
• Quality of life (QOL)

• High baseline levels of electrical resistance were observed.
• Fatigue decreased compared to the controls.

No significant differences were observed, but the study was underpowered and groups were not equivalent in symptoms at baseline.

• The very small sample led to a lack of power and inability to control covariates.
• Groups were not equivalent in baseline symptoms.
• The power estimates for QOL seemed inaccurate.
• No information was provided related to patient tolerance of treatment or adverse events.

Nurses should be trained in the use of AL-TENS and identification of acupuncture points. Future trials focused on fatigue are recommended.

To determine the pharmacokinetics, safety, and efficacy of two dosing regimens of APF530

There were two separate studies reported in this paper. The first study included 45 patients and used three escalating dosing schedules of 250 mg, 500 mg, or 750 mg. The second study included 35 patients with two dosing schedules of 250 or 500 mg. Safety and efficacy were reported. Drug levels were measured from predose to 168 hours after administration. Doses were given via subcutaneous injection in the abdomen prior to chemotherapy. All patients also received dexamethasone.

• N = 80
• MEAN AGE = 64 years (SD = 12.5 years [trial 1]), 55.7 years (SD = 8.7 years [trial 2])
• MALES: 40% (trial 1), FEMALES: 60% (trial 1), 100% (trial 2)
• KEY DISEASE CHARACTERISTICS: Ovarian cancer, breast cancer, lung cancer, lymphoma, leukemia, endometrial cancer, cervical cancer, vulvar cancer, colorectal cancer, bladder cancer, thymoma, and myeloma
• OTHER KEY SAMPLE CHARACTERISTICS: Chemotherapy regimens included carboplatin and combinations of cyclophosphamide-anthracycline, cyclophosphamide combinations, irinotecan, topotecan, cisplatin combinations, anthracycline, and gemcitabine-vinorelbine, among others.

• SITE: Multi-site    
• SETTING TYPE: Outpatient  
• LOCATION: Gabrail Cancer Center in Canton, OH; St. Louise Regional Hospital in Gilroy, CA; Department of Gynecologic Oncology at the University of Medical Science in Poznan, Poland

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

Prospective

• Plasma concentrations were measured.  
• Safety was assessed by vital signs, physical examinations, and clinical laboratory tests.  
• Twelve lead electrocardiograms were completed at screenings.  
• Symptoms were assessed with patient diaries.  
• Effectiveness was measured using diaries, information about the use of rescue medications, the number of emetic episodes, the number of retching episodes, and the number of nausea episodes for a seven-day period after the administration of medications.  
• Noncompartmental methods and descriptive statistics were used.

Both studies met the primary objective by defining pharmacokinetics. Adverse events did not appear to be dose-related. Most were mild to moderate and were unrelated to the study drug. Injection site reactions were low and were not associated with dosing, and 17.7% of erythema was reported in the 250 mg arm. No erythema was reported in the 750 mg arm. The plasma concentrations of granisetron were maintained for seven days with a single dose of the drug. Preliminary data demonstrated another option for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. Patients treated with APF530 at 250 or 500 mg obtained complete response 83% of the time in the acute-onset and delayed-onset phases. Complete control was obtained in 76%. Nausea was controlled almost as well as emesis. Nausea reports were mostly mild.

Granisetron exposure was maintained for seven days with a single dose of subcutaneous AFP530. Mild injection site irritation was noted. Nausea was mild, and nausea and vomiting were controlled in the acute and delayed phases.

• Small sample (< 100)
• 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)  
• Findings not generalizable

This could be another option for treating chemotherapy-induced nausea and vomiting, but it is possible that this treatment causes unnecessary discomfort when oral and transdermal approaches are available. This is very preliminary data, and the study did not compare this treatment to standard care. Additional research to determine the usefulness of this drug for chemotherapy-induced nausea and vomiting is needed.

PURPOSE: To review absorbable hemostatic agents including pharmacology, clinical efficacy, adverse events and toxicities, dosage and administration, and safety issues

Discusses nine different agents and the different composition of each (e.g., porcine or bovine gelatin, bovine collagen or oxidized cellulose). The two newest agents (approved as U.S. Food and Drug Administration devices, not drugs) are FloSeal^® and CoStasis^®, and these products include bovine thrombin.

• Absorbable agents provide hemostasis via contact activation (which initiates clotting) and/or promotion of platelet aggregation.
• Absorbable hemostatic agents are indicated for use during surgery when bleeding can not be controlled by conventional methods such as pressure.
• Emphasis that topical thrombin is for TOPICAL application only. Misadministration (e.g., IV) can be fatal.

• Literature on these agents is mostly case reports. There are few well-controlled trials that actually have compared agents and/or the efficacy of such agents specifically in instances of bleeding associated with malignancy. The summary of trials and reports is presented. Only 2 of the 14 trials had patients with cancer in the sample (patients with hepatocellular carcinoma undergoing elective hepatic resection and patients with gynecologic cancer undergoing exploratory laparotomy).
• Allergic reactions to thrombin can occur, as can development of antibodies to bovine components of the product.
• No standardized dosing regimens exist; the minimal amount of product needed to achieve hemostasis should be used. Follow product labeling, especially for newer agents such as FloSeal (Baxter) and CoStasis (Cohesion Technologies). A summary table for dosage and administration per each agent is provided.
• Good clinical data are lacking evaluating efficacy of these agents, especially for off-label use (e.g., in nasal packing for uncontrolled epistaxis in patients with thrombocytopenia).

To explore the effect of providing lymphedema information on breast cancer survivors’ symptoms and practice of risk-reduction behaviors

All data collection was completed in person. The first author was available to answer questions and assist participants with physical disabilities (i.e., to provide help with reading, marking, or writing). Data were collected from August 22, 2006–May 1, 2007 in New York City, NY.

• The study sample (N = 136) was comprised of female patients with breast cancer.
• Mean age of patients was 54 years.
• Seventy-four percent of patients were White, 59% were married, and 44% held a graduate degree.

The study took place at New York University Cancer Center.

The study used a cross-sectional, descriptive design.

The study used the Lymphedema and Breast Cancer Questionnaire to assess lymphedema-related symptoms and the Lymphedema Risk-Reduction Behavior Checklist.

Fifty-seven percent of patients reported that they received lymphedema information. On average, participants had three lymphedema-related symptoms. Only 18% of participants were free of symptoms. Participants who received information reported significantly fewer symptoms (t = 3.03, p < 0.00) and practicing more risk-reduction behaviors (t = 2.42, p = 0.01).

Providing lymphedema information has an effect on symptom reduction and more risk-reduction behaviors being practiced among survivors of breast cancer.

• The study used a cross-sectional design.
• The majority of the sample were highly educated and White.

In the study, nurses were ranked as the second-most important source of lymphedema information or education after pamphlets. In clinical practice, nurses and other healthcare professionals could consider taking the initiative to provide adequate and accurate information and engage survivors of breast cancer in supportive dialogues concerning lymphedema risk reduction

To evaluate the efficacy and toxicity of palonosetron (PAL) and dexamethasone (DEX) on day 1 versus 3 of Decadron in patients with gynecologic cancer receiving carboplatin and paclitaxel (TC); to evaluate the efficacy of a one-day versus three-day Decadron regimen (primary endpoint was complete response in the delayed phase)

All patients received an intravenous prophylactic of Decadron at 20 mg within 15 minutes of a PAL dose of 0.75 mg 30 minutes before chemotherapy. Patients in the DEX1 arn received no further Decadron. Patients in the DEX3 arm received Decadron on days 2 and 3 at 8 mg.

• N = 88  
• AVERAGE AGE = 59 years (DEX1), 62 years (DEX3)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Ovarian, cervical, and endometrial cancers
• OTHER KEY SAMPLE CHARACTERISTICS: Patients were receiving paclitaxel and carboplatin. All participants were chemotherapy-naïve.

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

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

Single-institution, prospective, randomized, open-label study

• Multinational Association of Supportive Care in Cancer (MASCC) Antiemesis Tool (MAT) for data collection in the first cycle
• The primary endpoint was complete response (CR) defined as no emetic episodes and no rescue medication in the delayed phase of the first cycle.
• The secondary endpoint was CR in the acute and in all phases of chemotherapy-induced nausea and vomiting (CINV). Complete control (CC) defined as no emetic episodes, no use of rescue medications, and no significant nausea defined as a MAT score less than 3.

The authors noted that there was no significant difference between groups in complete response, complete control, or total CINV in the acute and delayed phases. There was no significant difference between groups in the rate of severe nausea. The CR rates in the delayed phase were not statistically different in the three-day group (76.9%) versus the one-day group (69.8%). The use of palonosetron and Decadron appears to be equally effective in treatment of delayed CINV for patients receiving paclitaxel and carboplatin.

The use of Decadron was effective with one-day use compared to three-day use. The side effect profile of steroids is very robust, meaning that fewer days of their usage with good control could improve patients' quality of life.

• Small sample (< 100)
• Baseline sample/group differences of import
• Risk of bias (no control group)
• Risk of bias (no blinding) 
• Risk of bias(sample characteristics)
• Findings not generalizable
• Other limitations/explanation: The homogenous population in Japan would affect drug metabolism.

Based on the results of this study, dexamethasone is effective after only one day of use compared to three days of use. The side effect profile of steroids is robust, so fewer days of their use with adequate CINV control could improve patients' quality of life.

STUDY PURPOSE: To assess the effects of aerobic and resistance exercise on treatment-related side effects during adjuvant treatment for breast cancer

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 32 in review, 26 in meta-analysis
• TOTAL PATIENTS INCLUDED IN REVIEW = 2,626
• SAMPLE RANGE ACROSS STUDIES: 20–242 patients
• KEY SAMPLE CHARACTERISTICS: All were receiving adjuvant treatment for breast cancer

PHASE OF CARE: Active antitumor treatment

• Fatigue: SMD for in favor of exercise was –0.28 (95% confidence interval [CI] [–0.41, –0.16]) with moderate quality evidence (19 studies including 1,698 women).
• Depression: The difference with exercise was not significant, and evidence quality was moderate (5 studies including 674 women).
• Cognitive function assessed with Trail Making Test: MD –11.55 (95% CI [–22.06, –1.05]) with low quality evidence (2 studies including 213 women)
• Anxiety: Three studies assessed anxiety. A meta-analysis of two studies found no significant difference with exercise.
• A variety of other outcomes were assessed and reported, such as physical fitness, quality of life, and mood.

The findings show a moderate effect of exercise on fatigue among women receiving adjuvant treatment for breast cancer. No significant effects were seen for depression or anxiety. A statistically significant effect for cognitive function was found; however, the evidence was deemed to be of low quality.

• High heterogeneity
• The authors reported lack of sufficient information in reports to make clear judgments about potential bias.

Exercise probably reduces fatigue and improves physical fitness among women during treatment for breast cancer. Adherence to exercise can be a challenge, and implementation of exercise recommendations or programs will need to address factors to foster exercise participation to be successful.

To investigate the effect of dexamethasone (DEX) on fatigue and other toxicities in patients treated with regorafenib

Data were obtained from medical records for analysis. DEX was given to some patients prophylactically at the physician’s discretion at 2 mg/day throughout regorafenib treatment. Data from those given DEX versus those not given DEX were analyzed. Patients received 120–160 mg regorafenib on weeks 1–3 of each four-week cycle.

• N = 105, 31 received prophylactic DEX
• MEDIAN AGE = 63–63
• AGE RANGE = 38–80 years
• MALES: 52.4%, FEMALES: 47.6%
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: 
• OTHER KEY SAMPLE CHARACTERISTICS: The median follow-up period was 15.7 months, and the mean treatment duration was three months.

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

PHASE OF CARE: Active antitumor treatment

Retrospective cohort

Common Terminology Criteria for Adverse Events (CTCAE)

The most frequent adverse event leading to dose modification in both groups was hand-foot syndrome (55.6%). No patients in the DEX group had dose modification because of fatigue compared to 8% in the non-DEX group. Median time to dose modification was longer in the DEX group (p = 0.009). The incidence of fatigue was lower in the DEX group (25.8% versus 50%, p = 0.022). The incidence of at least grade 3 hand-foot syndrome was lower in the DEX group (3% versus 25.7%, p = 0.002). The incidence of oral candidiasis was greater in the DEX group (16.2% versus 0%, p < 0.001).

Systemic corticosteroids were associated with a lower incidence of more severe hand-foot syndrome but also associated with a higher incidence of oral candidiasis in this group of patients.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)

Prophylactic oral DEX was associated with reduced fatigue and incidence of hand-foot syndrome in patients receiving regorafenib. Systemic DEX may reduce some treatment side effects but was also associated with the development of oral candidiasis. Effectiveness of prophylactic DEX and associated adverse effects warrant further investigation. Nurses need to be aware of the potential infectious complications of patients receiving systemic corticosteroids, and the effects of long-term use needs to be investigated.