To identify an optimal dose of GCPGC and compare its safety and efficacy to that of pegfilgrastim

This study involved two phases—a phase II trial to identify optimal dosage followed by a phase III study to determine efficacy and safety of GCPGC in comparison to standard pegfilgrastim. In phase II, patients were randomized to receive either 3.6 mg  or 6 mg of GCPGC on day 2 of a cycle. There were no differences in neutropenic outcomes between groups, and researchers decided to use 6 mg for phase III. In phase III, patients were randomized to receive either 6 mg pegfilgrastim or 6 mg GCPGC on day 2 of their treatment cycle. Outcomes per treatment cycle were evaluated. During phase III, prophylactic antibiotics were not permitted in the first cycle but could be used in subsequent cycles according to physician discretion.

• N = 59 phase II, 117 phase III  
• MEDIAN AGE = 49 years phase II
• AGE RANGE = 28–74 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All had breast cancer and were scheduled to receive 4–6 cycles of docetaxel anddoxorubicin (DA) or docetaxel, doxorubicin, and cyclophosphamide (TAC) regimens

• SITE: Multi-site    
• SETTING TYPE: Not specified  
• LOCATION: South Korea

• PHASE OF CARE: Active antitumor treatment

• Noninferiority phase III, double-blind, multi-site randomized, controlled trial with active control

• Duration of grade 4 neutropenia during the first cycle (ANC < 500/mcl)
• Time to ANC recovery
• Incidence of febrile neutropenia (FN) defined as ANC < 500/mcl and with single oral temperature ≥ 38.3 C or two or more instances of temperature ≥ 38 C
• Hospital days
• IV antimicrobial usage

There were no significant differences in outcomes between groups other than time to ANC recovery. ANC recovery time after cycle 1 was a mean of 8.85 in the GCPGC group compared to 9.83 in the pegfilgrastim group (p < 0.0001). Incidence of treatment delay or dose reduction was higher in the pegfilgrastim group (p < 0.09). Adverse drug reactions that may have been associated with the study drug were 5.3% in the GCPGC group and 3.4% in the pegfilgrastim group, and included dizziness, eukocytosis, blurred vision, injection-site pain, pyrexia, headache, and peripheral sensory neuropathy.

GCPGC was not inferior to pegfilgrastim for prevention of febrile neutropenic complications in women receiving myelosuppressive chemotherapy. Additional research is needed to confirm its efficacy and safety.

• Risk of bias (sample characteristics)

GCPGC provided similar results as pegfilgrastim in terms of neutropeni- related complications with this type of myelosuppressive chemotherapy. However, adverse events appeared to be somewhat higher in the GCPGC group. Additional research is needed to confirm the safety profile of this new CSF.

To examine the cost-benefit of primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) in patients with non-Hodgkin lymphoma (NHL) receiving cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) chemotherapy

In 2007, the study site implemented standard primary prophylaxis with G-CSF in this group of patients. Outcomes were compared to a historical control group that had not received primary prophylaxis. Analysis of cost was based on institutional direct costs for treatment of febrile neutropenia (FN).

• N = 65
• MEDIAN AGE = 61 years
• AGE RANGE = 20–85 years
• MALES: 51%, FEMALES: 49%
• KEY DISEASE CHARACTERISTICS: All had NHL and were receiving R-CHOP chemotherapy
• OTHER KEY SAMPLE CHARACTERISTICS: Patients receiving hematopoietic stem cell transplantation were excluded.

• SITE: Single site
• SETTING TYPE: Inpatient 
• LOCATION: New Zealand

• PHASE OF CARE: Active antitumor treatment

• Retrospective, descriptive, two-group comparison

• Incidence of FN

Patients who received primary G-CSF prophylaxis were compared to a group of patients who did not receive primary prophylaxis prior to 2007, when primary prophylaxis was instituted as the standard of care for these patients. Among those who received prophylaxis, the incidence of FN was 5%, compared to 60% of those who had not received prophylaxis (p < .0001). Cost-benefit analysis using the number needed to treat and the average cost of an FN episode showed that prophylaxis increased the cost by $238 (New Zealand dollars), including only direct costs.

Primary G-CSF prophylaxis was associated with a significant reduction in the incidence of FN for a small additional cost of overall care throughout CHOP chemotherapy.

• Small sample (less than 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement/methods not well described
• Findings not generalizable
• Other limitations/explanation: The definition of FN used in the study is not provided. Costs may not be applicable to those in other countries.

Primary G-CSF prophylaxis was associated with significantly lower prevalence of FN. Based only on direct healthcare costs, this study showed that primary prophylaxis was associated with a small, incremental increased cost, but these data do not account for other indirect costs and the full range of healthcare utilization that may be associated with treatment of FN. The authors concluded that primary prophylaxis in this group of patients was cost-effective. The cost-benefit of primary G-CSF prophylaxis has been a recent area of interest in oncology care. Further, well-designed economic analyses would be useful in exploring these questions among varied groups of patients.

To investigate whether a web-based self-management exercise and diet intervention (WBSEDI) is feasible and effective in patients with breast cancer to promote exercise and diet

Control versus 12-week WBSEDI. WBSEDIs were encouraged to be completed at least twice weekly. Education content included enhancing exercise and diet behavior in survivors; the importance of weight management; barriers to sustaining exercise and diet; planning exercise and diet; outcomes of regular exercise and diet; and exercise and diet recommendations for cancer survivors. Content was divided into modules based on patients' stage of change. The type and duration of exercise was decided by the patient. Diets were based on daily calorie requirements and food-group unit recommendations. Automatic feedback was provided in the module. The control group received a 50-page booklet of module information without transtheoretical model use.

• N = 57  
• MEAN AGE: 43.2 years (control group), 41.5 years (experimental group)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Mean time since treatment = 156.6 days (control), 161.6 days (experimental). 43/59 patients had breast-conserving therapy, 49/59 patients received chemotherapy, and 52/59 patients received radiotherapy. All participants completed primary therapy within last 12 months before study enrollment.
• OTHER KEY SAMPLE CHARACTERISTICS: Percent completing college or beyond: Control 69%, experimental 76.7%

• SITE: Multi-site    
• SETTING TYPE: Home    
• LOCATION: South Korea

• PHASE OF CARE: Late effects and survivorship

Pilot randomized controlled trial

• Primary outcomes: Exercise and fruit and vegetable intake, dietary quality using diary and recall.  
• Secondary outcomes: Health-related quality of life (HRQOL) using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ–C30) 
• Anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) 
• Fatigue using the Brief Fatigue Inventory (BFI) 
• Stage of change using open-ended questions 
• Perceived self-efficacy using Likert scale

89% of the experimental group consistently participated in the intervention. There was a significant increase in the intervention group for moderate-intensity exercise of 150 minutes per week (p < .0001) and five servings fruits and vegetables per day (p = .001). Secondary outcomes were significant improvements in the intervention group at 12 weeks for physical functioning (p = .023), fatigue (p = .032), and appetite loss (p = .034). The stage of change for exercise and fruit and vegetable consumption was significantly higher (p < .0001 and p = .029).

The intervention arm had a low attrition rate with a high percentage of participation. Secondary outcomes such as fatigue were associated with improved primary outcomes, suggesting increased exercise and improved diet can have an effect on quality of life and function for breast cancer survivors. Patient stage of change can affect participation in interventions. The cost and implementation of web-based intervention was not discussed, which may limit some institutions in using it.

• Small sample (< 100)
• Risk of bias (no blinding)
• Intervention expensive, impractical, or training needs
• Other limitations/explanation: Large number of identified patients excluded from study (113/172)

Web-based interventions may be effective for patients seeking lifestyle interventions that include ongoing support and feedback.

PHASE OF CARE: Multiple phases of care

Insufficient data to make recommendations regarding safety or efficacy of moxibustion on fatigue among Chinese patients with cancer

Insufficient data to make recommendations regarding safety or efficacy of moxibustion on fatigue among Chinese patients with cancer

• High risk of bias among studies (CONCERT and STRICTA)
• Low quality of reporting among studies
• Findings not generalizable (all subjects from inpatient Chinese population)
• Use of daily treatment schedules
• Lack of placebo or sham controls
• Methodological flaws
• Lack of blinding procedures
• Single measure of fatigue (Piper Fatigue Scale)
• Mention of adverse effects omitted with exception of one case of blistering.

Techniques of moxibustion requires specialized training not usually available in United States. Access to qualified practitioners, lack of an appropriate placebo or sham control, and frequency of treatment administration to outpatients would make additional studies of safety and efficacy difficult for nurse researchers to conduct.

To review and evaluate the evidence on the effect of ginger as a modality for management of chemotherapy-induced nausea and vomiting (CINV)

Databases searched were MEDINE, CINAHL, Embase, Cochrane central register, Korean Studies information service system, and dissertation central.

Search keywords were chemotherapy, nausea, vomiting, chemotherapy induced nausea and vomiting, ginger, ginger extract and Zingiver officinale.

The reference lists of retrieved articles also were reviewed.

The inclusion criteria were not specifically stated, but all studies were double blind randomized controlled trials (RCTs).

The exclusion criteria were not stated. However, specific studies that combined ginger with another treatment, did not include sufficient information about the sample and intervention, and examined outcomes per episode of chemotherapy rather than by patient were excluded.

• A total of 11 RCTs were initially identified.
• Reviewers used the Jadad scale to evaluate study quality.

• Five studies were included in the final review.
• Study samples ranged from 17-576 patients.
• Studies involved various cancer types and various chemotherapy emetic potentials.

All patients were in active antitumor treatment.

Three of the studies compared ginger to placebo, and two compared it to metoclopramide or ondansetron. Most of the trials did not use an NK1 in the antiemetic regimen, which is the current recommended guideline. Side effects reported with ginger included drowsiness, sleepiness, dry mouth, thirst, heartburn or restlessness. One study reported bruising, flushing, or rash. Meta-analyses concluded that ginger had no significant effect on control of acute or delayed nausea or vomiting.

Results do not support the use of ginger and did not show an antiemetic effect of ginger for management of CINV.

• The number of studies included in the review was limited.
• The meta analysis had high heterogeneity. 
• Not all studies specified the chemotherapy used and one study combined use with low, moderate, and high emetogenic chemotherapy regimens. 
• Most antiemetic regimens used with ginger did not incorporate current treatment guidelines for CINV.

Ginger does not appear to be effective for the management of CINV.

To evaluate the efficacy and safety of azasetron compared to ondansetron in the prevention of delayed chemotherapy-induced nausea and vomiting (CINV)

• Day 1: Azasetron 10 mg IV 30 minutes to 2 hours before chemotherapy and dexamethasone 20 mg IV 30 minute before chemotherapy
• Days 2–6: Azasetron 10 mg PO, placebo PO BID, dexamethasone 4 mg PO BID on days 2–4

• Day 1: Azasetron 10 mg IV 30 minutes to 2 hours before chemo and Dexamethasone 20 mg IV 30 minutes before chemo
• Days 2–6: Placebo PO, ondansetron 8 mg PO BID, and dexamethasone 4 mg PO BID on days 2–4

• N = 262  
• MEAN AGE: 58 years (range = 20–75 years)
• MALES: 74%, FEMALES: 26%
• KEY DISEASE CHARACTERISTICS: Multiple sites of cancer were included in the study
• OTHER KEY SAMPLE CHARACTERISTICS: Moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC)

• SITE: Multi-site    
• SETTING TYPE: Not specified  
• LOCATION: Korea

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

A multi-center, prospective, randomized, double-dummy, double-blind, parallel-group trial.

Patients completed daily logs for nausea and vomiting frequency with visual analog scales (VAS) on days 1–6 post chemotherapy administration. Tests were administered on day 7 and week 4 +/– one week. The primary endpoint was the effective ratio of complete response for CINV, and the secondary end points were degree of nausea by treatment day (grade 0–3), complete control (CC of vomiting and nausea) by treatment day, physician’s global assessment (PGA) score on day 7, and VAS by treatment day. There was no significant difference between groups on the secondary endpoints.

The authors acknowledge that azasetron has shown safety and efficacy with CINV in previous studies. However, the effectiveness of azasetron (45%) and ondansetron (54.5%) towards a complete response to CINV did not support azasetron’s superiority over ondansetron.

Azasetron showed inferiority for controlling delayed CINV when compared to ondansetron. The authors recommend that further studies about 5-HT3 receptor antagonists are not necessary; the superiority of NK1 receptor antagonists is documented. There was no difference between the groups for degree of nausea or complete control by treatment day.

Other limitations/explanation: The authors did not identify limitations for the study. The data were gathered between May 2005 and December 2005 and may be “dated.” Azasetron is only available in Japan at this time. Day 7 visit was missed by 21 patients.

Findings will assist nurses with the prevention of CINV for patients receiving moderate to high levels of emetogenic chemotherapy. Azasetron was not found to be superior to ondansetron for the prevention of CINV for patients receiving moderate to high levels of emetogenic chemotherapy.

To test the effects of an integrative, supportive intervention program for caregivers on caregiver strain and burden

Face to face sessions were done with caregivers to assess categories of caregiver burden, and then individually tailored interventions were provided in 30–40 minute individual sessions every two weeks until the patient expired. Telephone calls were done every other week to provide support and redirection to address areas of strain and burden. The intervention involved education, counseling regarding coping strategies, assistance in findings needed resources, and the provision of respite patient care. Patients in a different ward were allocated to a control group and received usual care. Usual care did not include proactive assessment to determine interventions. Ward assignment to control and intervention groups was done randomly. Participants were recruited when hospitalized and followed longitudinally. Data were collected every two weeks. All participants had access to a 24-hour help line.

• N = 81
• MEAN AGE = 50.7 years
• MALES: 18.5%, FEMALES: 81.5%
• KEY DISEASE CHARACTERISTICS: Various cancer types, with gastrointestinal most prevalent; all were end-stage
• OTHER KEY SAMPLE CHARACTERISTICS: 82% of caregivers lived with the patient, and more than 50% of caregivers spent greater than 16 hours per day caregiving.

• SITE: Single site  
• SETTING TYPE: Multiple settings  
• LOCATION: China

• PHASE OF CARE: End of life care
• APPLICATIONS: Palliative care 

Randomized, controlled, cohort, longitudinal trial

• Caregiver Reaction Assessment Tool (CRAT)
• Heart rate variability via handheld device 
• McCorkle Symptom Distress Scale (MSDS)
• Enforced Social Dependency Scale (ESDS)
• Caregiver Self Efficacy Scale (CSES)

The analysis showed a significant group by time effect for caregiver burden scores (eta square 0.49, p < 0.001) and self-efficacy scores (eta square 0.46, p < 0.001). Those in the intervention group had higher self-efficacy and lower burden. There were no significant differences in patient symptom severity between groups.

The proactive assessment of caregiver stressors and individualized supportive and psychoeducational interventions reduced caregiver strain and burden and increased caregiver self-efficacy.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Measurement validity/reliability questionable 
• Findings not generalizable
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: Usual care was not well-defined. It was not clear how many in the control group availed themselves of similar assistance upon request. Multiple repeated measures and possible testing effects existed.

This study demonstrated that purposeful caregiver assessment and individualized planned interventions to support caregivers and work with them regarding their stressors was effective in reducing subjective caregiver strain and burden and improving self-efficacy during the last three months of the patient’s life. This study provided frequent caregiver contact with reassessment, enabling the identification of and response to changing needs.

To examine the benefits of a single-session psychoeducational intervention using a tablet PC during chemotherapy

Patients were assigned to intervention or control groups according to their dates of informed consent rather than strict randomization. Study measures were obtained at baseline and two to four weeks later. The study group was given a single-session psychoeducational intervention using a tablet PC to administer the education.

• N = 19 (intervention), 17 (control)  
• AVERAGE AGE = 57.5 years
• MALES: 45%, FEMALES: 55%
• KEY DISEASE CHARACTERISTICS: Patients with cancer undergoing chemotherapy
• OTHER KEY SAMPLE CHARACTERISTICS: The majority of participants were married and were diagnosed with stage IV cancer with an Eastern Cooperative Oncology Group score of 1. All participants scored 11 or more on anxiety and depression scales.

• SITE: Single-site    
• SETTING TYPE: Outpatient    
• LOCATION: Seoul, South Korea

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

Two-group trial

• Hospital Anxiety and Depression Scale (HADS)
• Short Form-8 Health Survey (SF-8)
• Insomnia Severity Index (ISI)
• Impact of Event Scale–Revised (IES-R)

Compared to the control group, the intervention group showed a positive score change on the HADS scale. The mental component summary score of the SF-8, the IES-R avoidance subscale, the ISI, and the total score of the HADS scale were the following. HADS (p = .0002), SF-8 (p = .011), ISI (p = .021), and IES-R (p = .036) declined from baseline more in the intervention group. Scores did decline in both groups.

A tablet-based, 20-minute psychoeducational intervention could be an effective intervention for managing depression, sleep disturbance, and quality of life.

• Small sample (< 100) 
• Risk of bias (no random assignment)
• Risk of bias (sample characteristics)
• Key sample group differences that could influence results
• Intervention expensive, impractical, or training needs
• Other limitations/explanation: Patients needed to understand how to use a tablet PC. Patients had to be able to hear and understand the tablet PC. Patients had to be undergoing chemotherapy. Tablet PCs are expensive. There was a high refusal rate to participate in the study.

To explain the relationship between the intensity of chemotherapy-induced nausea and vomiting (CINV) and the frequency of P6 digital acupressure in a group of patients with breast cancer who received moderately to highly emetogenic chemotherapy and applied P6 digital acupressure as an additional intervention for CINV control.

This was a secondary analysis of a multicenter, longitudinal, randomized, clinical trial that compared differences in CINV among three groups (P6 acupressure, placebo digital acupressure, and usual care). The original study was published in 2007.

Patients in the group receiving P6 acupressure in the parent study were instructed to perform digital acupressure for three minutes or point release at the P6 points on both arms in the morning plus an additional three minutes of acupressure to one arm whenever nausea occurred. Secondary analysis was conducted of this group’s data from the patient information questionnaire and daily log.

• The study consisted of 53 participants.
• Participant mean age was 49 years (SD = 10.55) with a range of 27–74 years.
• All of the participants were female patients with breast cancer who were beginning their second or third cycle of moderately to highly emetogenic chemotherapy (cyclophosphamide with or without 5-fluorouracil; doxorubicin with paclitaxel or docetaxel; or 5-fluorouracil, epirubicin, and cyclophosphamide).
• All participants had been in the group in the parent study which applied P6 digital acupressure in addition to antiemetics to control CINV.
• All participants had had a nausea intensity score with previous chemotherapy of at least 3.

This was a multisite study conducted at 15 different sites in the United States.

All patients were in active treatment.

The study was design was a descriptive secondary analysis.

• A Patient Information Questionnaire was used to record demographic information and predisposing factors.
• A disease and treatment questionnaire was used to collect medical information.
• Participants recorded nausea and use of P6 digital acupressure each evening in daily logs for 11 days after chemotherapy.
• Nausea was measured on a 0-10 nausea intensity numeric rating scale (NRS) and on the 0-12 nausea score from the Index of Nausea, Vomiting and Retching (INVR). Interrater reliability for these two scales has been reported as having a significant high correlation (r = 0.75–0.95).

• The average amount of acupressure use over 11 days was two times per day.
• Participants used acupressure for an average of seven days after chemotherapy.
• The most frequent day of acupressure was day 3.
• An increase in nausea intensity ratings from days 1–3 was not associated with the frequency of acupressure (incidence rate ratio [IRR] = 0.96; p = 0.02).
• A decrease in nausea intensity ratings for days 4—11 was associated with the frequency of the acupressure (IRR = 1.11; p < 0.01).
• Women who used acupressure more than five times on day 4 experienced the highest nausea intensity over the 11 days, and their peak of nausea intensity was different from the other groups. Hierarchical generalized linear model (HGLM) analysis did not support this difference as significant.
• Age was the only significant predisposing factor for nausea intensity in the acute phase. With each year increase in age, a significant decrease in NIR and the use of acupressure on day 4 was found.

Nausea intensity was not found to be consistently related to frequency of acupressure use.

Types and dosages of antiemetics used were not described.

Based on the results of the parent study and the indepth secondary analysis of the acupressure group, patients with CINV may benefit from P6 acupressure throughout the first 11 days after chemotherapy. Because each patient is different, individualized patient teaching and resources for managing CINV are important.

To evaluate the use of sorbitol as an inexpensive alternative to lactulose for treating constipation in older adults.

Lactulose and 70% sorbitol (0–60 ml daily) were given for four weeks. During the treatment period, patients were instructed to begin taking 30 ml of the study laxative at bedtime, thereafter adjusting the dose as needed from 0–60 ml. Patients were instructed to maintain high dietary fiber and avoid sources of free fructose such as apples and pears.

The length of the wash-in and washout periods was based on previous studies, which showed up to three to four days are required for lactulose to take effect and the carryover effect after cessation of lactulose is about six to seven days. The study began with a two-week lead-in period, during which patients received lactulose in a single-blind fashion. This was followed sequentially by washout period A (two weeks), treatment period A (four weeks), washout period B (two weeks), and treatment period B (four weeks). The purpose of the lead-in period was to ensure (a) the patient tolerated lactulose, (b) the patient understood how to fill out the diary, and (c) the conditions preceding the two treatment periods were similar. At the end of washout period A, patients were randomly assigned to receive one of the two study laxatives in treatment period A, with the other laxative being used in treatment period B.

The primary endpoints of the study were average number of bowel movements per week and the average number of days per week on which bowel movements occurred.

• The study reported on a sample of 40 ambulatory men. However, only 30 patients were accounted for (see Setting).
• Mean patient age was 72 years (range 65–86).
• Patients were included in the study if they had a history of constipation for a duration of at least one year. The study was designed to recruit ambulatory patients with the most severe constipation who were not taking narcotics.
• Twenty-one patients took bulk-forming agents throughout the study (psyllium in all cases).

• Minneapolis Veterans Affairs Medical Center in Minnesota from September 1988 to July 1989
• Five patients were residents of the Minnesota Veterans Home and the other 25 were outpatients.

This was a randomized, double-blind, crossover study.

• A patient diary was used to record bowel consistency (hard, soft, or loose), daily dose of study laxative, use of any other laxative or enema, and occurrence and severity of seven symptom categories (bloating, cramping, excessive flatulence, nausea, diarrhea, fecal incontinence, and other).
• Statistical analysis: t-test method for crossover trials (two-sided alpha)

• Thirty patients completed the study. Nine withdrew prior to randomization because of lactulose intolerance, and one patient dropped out after randomization.
• No significant differences existed between sorbitol and lactulose in any outcome measured except nausea, which increased with lactulose use (p < 0.05).
• Mean number of bowel movements per week was 6.71 with sorbitol and 7.02 with lactulose (95% confidence interval [CI] of the difference [–0.43, 1.06]).
• Mean number of days per week with bowel movements was 5.23 with sorbitol and 5.31 with lactulose (95% CI of the difference [–0.32, 0.48]).

The results supported the hypothesis that sorbitol and lactulose have no clinically or statistically significant difference in laxative effect. Sorbitol can be recommended as a cost-effective alternative to lactulose for the treatment of constipation in older men.

• The study had a short duration and was limited to ambulatory older men. Caution should be used in extrapolating these findings to women, younger patients, or those who are bedridden.
• The withdrawal of patients because they did not tolerate lactulose may have biased the study.
• The sample size was smaller than the 32 patients required to provide sufficient power for statistical significance of the results.