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.

To investigate whether a communication skill training program for nurses would reduce psychological distress and improve coping among patients newly diagnosed with cancer

The communication skill training (CST) program involved two workshops, one at the start of the study and the other after three months. Workshops lasted six hours and were structured in a six-step approach (SPIKES) involving (1) setting up the interview, (2) assessing the patient’s perception of his or her illness, (3) obtaining a patient invitation to disclose information, (4) giving information and knowledge to the patient, (5) addressing the patient's emotion with empathic responses, and (6) strategy and summary. The program involved a large group meeting on theoretic content followed by small facilitated group work in which nurses worked through various scenarios using the SPIKES steps. Study patients were randomly assigned to be interviewed three times by nurses who attended the CST program (experimental group) or interviewed the same three times by nurses in the control group. Interviews were scheduled on the day of diagnosis, and one week and one month after diagnosis. Study measurements were done at one week after diagnosis (T1), one month after diagnosis (T2), and three months after (T3). Nurses were randomly assigned to either CST or usual care provision.

• The study reported on a sample of 89 patients, plus 8 nurse participants.
• Mean patient age in the experimental group was 61.4 ± 10.8 years; mean patient age in the control group was 60.9 ± 14.3 years.
• The sample was 56%–61% female and 39%–40% male.
• Patients had gastric, colorectal, and breast cancers.
• More than 90% of study patients had surgery, 76%–81% were married, 39%–44% were unemployed, and more than 50% in both groups had stage I disease.
• Nurse participants had a mean age of 40.8 ± 7.2 years, and mean years of experience as an oncology nurse of 17.2 ± 6.87.
• Inclusion criteria included patients who were newly diagnosed and informed of cancer in physician consultation, were older than age 18, and had disease that was not advanced and at an operable stage.
• Patients were excluded if they had a severe psychological problem as assessed by the physician.

• Single site
• Outpatient setting
• Japan

Patients were undergoing the diagnostic phase of care.

A randomized controlled trial design was used.

• Hospital Anxiety and Depression Scale (HADS)
• Mental Adjustment to Cancer Scale (MAC)

There was a significant different in HADS depression and total scores over time associated with group (p = 0.03). These scores declined over time in both groups; however, the decline was greater for the experimental group. There was no group interaction or for anxiety. There were no significant changes in any other HADS data. MAC score changes over time showed mixed results. The only consistent directional change in the experimental group, as compared to the control group, was in the area of fatalism, with decline over time in the experimental group and increase over time in the control group (p = 0.04).

CST appears to have a positive effect on psychological distress and some areas of coping for patients newly diagnosed with cancer.

• The study sample was small, with less than 100 participants.
• The study sample was purposefully homogeneous in terms of diagnoses, disease stage, and phase of care, and findings may not be applicable to other patient groups.
• Nurses in the study had extensive years of experience in cancer care. The CST described here may not have similar effects with nurses who are less experienced in general or in oncology care.
• The authors point out that results may have been influenced by the cultural attitude of Japanese patients and poor support systems that are seen to exist in Japan for newly diagnosed patients. These patients tend to not seek professional assistance, so the magnitude of differences in results may not be the same for other cultural groups in which professional support is more available or acceptable.
• There was no credible evaluation of actual communications between nurses and patients or between physicians and patients that may have also influenced findings. In addition to study nurses, nurses in charge who had not been trained were always present at physician consultations and were involved in patient support afterward. There is no way to tell if charge nurse interactions were different between groups, changed over time, or were influenced by interaction with CST-trained nurses.

Study findings support the idea that providing information, support, and empathic responses to patients can positively influence patient coping and emotional distress, and suggest that nurse training in communication skills of this nature can be useful. Further research in this area needs to demonstrate actual differences in communications between nurses and patients as a result of such training. It would be useful to see if such training can be beneficial in various groups of nurses based on differences in nursing education level and experience.

To determine whether an intervention could improve antiemetic guideline adherence and the control of chemotherapy-induced nausea and vomiting (CINV)

Evidence-based antiemetic medication information was provided as notification to physicians in a view format. The description of the intervention was not clear, and it was presumed that the notification was provided in some manner through the electronic medical record system. CINV control after the intervention was compared to CINV control in a cohort of patients treated prior to the intervention.

• N = 125 (64 in intervention group)
• MEAN AGE = 64.2 years
• MALES: 71%, FEMALES: 29%
• KEY DISEASE CHARACTERISTICS: All patients had colorectal cancer and were receiving moderately emetogenic chemotherapy.

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

• PHASE OF CARE: Active antitumor treatment

Cohort comparison

• Complete protection in the acute and delayed periods was defined as no vomiting and protection from nausea.

The dosage of oxaliplatin or irinotecan was higher in the intervention group (p < 0.01). In the observational group, adherence to guidelines was 100% in the acute phase and 6.6% in the delayed phase. Nonadherence was caused by the lack of a prescription of dexamethasone on days 2 and 3. After the intervention, adherence to the administration of dexamethasone was 89%. In the intervention group, the complete protection rate was 20% higher after the intervention (p < 0.05), but adherence during the acute phase dropped and was significantly lower in the intervention group (p < 0.01). The incidence of leukopenia was higher in the intervention group (42.2% versus 23%, p = 0.024). There were no other differences in toxicity.

The intervention used in this study had mixed results in terms of adherence to CINV antiemetic guidelines and control of CINV in acute and delayed phases.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Key sample group differences that could influence results
• Measurement validity/reliability questionable
• Other limitations/explanation: The intervention group was significantly older. The exact intervention was not well described. The definition and method of measurement of CINV outcomes were not well described.

In this study, an organizational intervention had mixed results in improving adherence to antiemetic guidelines and patient CINV outcomes. The findings were limited by the lack of detail regarding the specific intervention used, but it appears to have been a notification in the medical record with no other action. Organizational initiatives to improve practice are not all created equally, and such studies need to provide sufficient detail about the actual intervention to determine if approaches that are effective in creating practice changes and improvements in patient outcomes.