To evaluate the efficacy of aprepitant plus a standard antiemetic regimen (granisetron plus dexamethasone) in preventing CINV for patients with multiple myeloma receiving high-dose chemotherapy and autologous stem-cell transplantation (ASCT)

Patients randomly were assigned to receive either aprepitant (125 mg orally on day 1 and 80 mg orally on days 2–4) plus granisetron (2 mg orally on days 1–4) and dexamethasone (4 mg orally on day 1 and 2 mg orally on days 2–3) or a placebo plus granisetron (2 mg orally on days 1–4) and dexamethasone (8 mg orally on day 1 and 4 mg orally on days 2–3). High-dose chemotherapy (melphalan 100 mg/m²) was administered on days 1–2, and ASCTs were performed on day 4.

• N = 362
• MEAN AGE = 58.1 years
• MALES: 230 (64%), FEMALES: 132 (36%)
• KEY DISEASE CHARACTERISTICS: Multiple myeloma
• OTHER KEY SAMPLE CHARACTERISTICS: High-dose chemotherapy; receiving ASCT

• SITE: Single site    
• SETTING TYPE: Inpatient  
• LOCATION: Large university hospital in Germany

• PHASE OF CARE: Active antitumor treatment

Prospective, placebo-controlled, randomized, double-blinded, parallel-group, single-center study

• Functional Living Index–Emesis (FLI-E) questionnaire to record quality of life
• Daily diary with a 100 mm Visual Analog Scale (VAS) to record episodes and severity of nausea and vomiting

Patients receiving aprepitant plus standard antiemetic therapy were significantly more likely to achieve complete response (no emesis and no rescue therapy within 120 hours of melphalan administration) (p = 0.0042), were significantly more likely to be without major nausea (p = 0.026) and emesis (p = 0.0036) within 120 hours of melphalan administration, and had a higher quality of life (p < 0.001) compared to the placebo plus standard antiemetic therapy group.

The addition of aprepitant to standard antiemetic therapy resulted in significantly less CINV and a positive effect on quality of life.

The addition of aprepitant to standard antiemetic therapy not only reduced CINV but also improved quality of life for patients receiving ASCT.

IV palifermin 60 mcg/kg per day was given for three consecutive days before chemotherapy cycle A2 or B2 and then for three consecutive days after chemotherapy. All patients received granulocyte colony-stimulating factor (G-CSF). Prophylactic treatment consisted of a number of agents, including tetracaine, chamomile, oral hygiene, and amphotericin B suspensions. Authors used previous studies as historical controls.

This study used a retrospective series of 10 patients with B cell acute lymphocytic leukemia (ALL) or aggressive B cell lymphoma. Patients had World Health Organization (WHO) Oral Mucositis grades of 3 or 4 during cycle A1 or B1 of high-dose methotrexate (HDMTX).

Patients were selected retrospectively from September 2004 to March 2007.

• WHO mucositis grading was obtained daily.
• Opioid use was recorded.

• Sixteen episodes of grade 4 and one episode of grade 3 mucositis were observed without palifermin.
• One episode of grade 4, four episodes of grade 3, and four episodes of grade 2 mucositis were observed with palifermin (p < 0.05).
• IV opioids were reduced from 2,403 mg to 640 mg morphine (p < 0.05).
• Duration of higher grade mucositis was reduced slightly from 12.9 days to 11 days (not significant).

• The sample size was very small.
• Historical controls were used.
• Other prophylactic measures may have had effects.
• No discussion of cost was provided.

To study the safety and effectiveness of training with a mechanical arm crank on lymphedema development after axillary node dissection

Patients were randomized to usual care or supervised training sessions with an arm crank. The training group had exercises for strength and endurance for 60 minutes twice weekly for 12 weeks. The training involved either passive motorized training, motor supported self-training, or training by patient-generated power alone. The training modality used depended on patient performance. Study outcome measures were obtained before and after study-related training.

• N = 49   
• MEAN AGE = 57
• FEMALES: 100%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Breast cancer. All underwent axillary node dissection, and the majority had postoperative radiotherapy.

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

PHASE OF CARE: Late effects and survivorship

Randomized, controlled trial

• Body mass index
• Bioelectric impedance analysis (BIA)
• Arm circumference measurement
• Muscular strength—isometric capacity testing for latissimus dorsi and pectoralis muscles 
• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-20 (EORTC QLQ C-30)
• Borg scale for effort during training sessions

An increase in lean body mass was observed in patients in the training group (p = 0.017) and decrease in body fat (p = 0.009). Muscular strength increased in both groups. No significant differences existed between groups in arm volume changes. Both groups showed a significant reduction in arm volume from baseline to the end of the study (p < 0.01).

No increase in lymphedema volume was reported with the training provided with the arm crank. This training did not improve lymphedema management compared to usual care.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• No description of usual care

The findings showed no increase in lymphedema with arm training using a mechanical training device. The use of this device appeared to be safe but was no more effective for arm volume reduction than whatever was provided as usual care.

STUDY PURPOSE: To assess the effects and tolerability of buprenorphine for cancer-related pain in adults and children

• FINAL NUMBER STUDIES INCLUDED = 19 
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,421
• SAMPLE RANGE ACROSS STUDIES: 10–189 patients
• KEY SAMPLE CHARACTERISTICS: Not provided

APPLICATIONS: Palliative care

Five studies looked at sublingual buprenorphine versus another formulation, tramadol (one), or pentazocine (two). Pain ratings did not differ significantly from those for tramadol. Buprenorphine was associated with better pain relief than pentazocine. Transdermal buprenorphine was compared to a placebo, controlled-release morphine, or transdermal fentanyl. Pain scores did not differ significantly from fentanyl and were lower in comparison to controlled-release morphine. Intramuscular, epidural, or IV buprenorphine was not substantially different in pain reduction compared to morphine given via the same routes.

Although buprenorphine evidence was limited and of low quality, the findings of this analysis suggested that buprenorphine was an effective pain reliever. The evidence was insufficient to suggest buprenorphine as a first-line treatment choice.

• Low quality studies
• Very few studies with the same comparisons for evaluation
• Very little evidence in children

Buprenorphine appeared to be an effective analgesic for cancer-related pain although the limited evidence for various formulations and comparisons suggested that it was not the most appropriate choice for first-line treatment. Buprenorphine may be useful in patients who receive opioid switching, or for whom alternatives to standard analgesic choices are needed.

To evaluate the effect of gentle strength training on endurance and psychological outcomes in patients with breast cancer.

Patients were randomized to the intervention or control study groups. Patients in the control group participated weekly in gymnastic exercises, such as chair or floor exercises with various sports equipment. Those in the intervention group were trained with strength endurance training, according to individualized training plans based on a training load of 50% of one repetition maximum on a weekly basis. Both groups continued the weekly training program for six months. Data were collected at baseline, after three months, and after six months.

• Thirty-three participants (100% female) were included. 
• Mean age was 56 years.
• All participants had breast cancer and had completed initial antitumor treatments. 
• Participants were an average of approximately nine months since diagnosis.

• Single site 
• Other setting
• Germany

Patients were undergoing the transition phase after active treatment.

This was a randomized, two-group prospective study.

• Endurance test using a bicycle ergometer
• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-BR-23) module for quality of life (QOL) and fatigue
• Body mass index (BMI)

There was a significant reduction in BMI in both groups. QOL and fatigue scores showed a significant improvement in both groups at three and six months (p < 0.01). There were no significant differences between groups. The pattern of fatigue change showed decline in both groups by three months. At the six-month time point, the intervention group continued to experience a decline, whereas those in the control group showed increased fatigue, although this level was still below that at baseline.

Both conventional gymnastic exercise and gentle strength training were associated with weight reduction and improvement in fatigue and QOL in women with breast cancer.

• The study had a small sample size, with less than 100 participants.    
• Baseline sample/group differences were of import.
• The study had risks of bias due to no control group and no blinding.
• Measurement validity/reliability was questionable.*
• * Baseline QOL measures were higher in the intervention group.  There was no information provided regarding patient adherence to weekly sessions.  Fatigue was only measured with a single item from the instrument used.  It was not clear whether patients had relevant levels of fatigue at baseline or if all exercise was supervised or if individuals performed the sessions on their own.

Findings suggested that both types of exercise were beneficial to patients with breast cancer.  Further research in this area would be beneficial to determine those types of exercise and the timing of exercise related to cancer treatment that are most effective for the prevention and management of fatigue.

To evaluate the effects of a 12-week resistance training intervention in patients with breast cancer during adjuvant chemotherapy

Patients were randomly assigned to the intervention or attention control group. The control group received a supervised group muscle relaxation program with the same session schedule as the intervention group. The exercise intervention involved the use of eight different machine-based progressive resistance exercises without an aerobic component. Both interventions were provided in group settings for 60 minutes twice weekly. Study measures were obtained at baseline and at the end of the intervention period.

• N = 95
• MEAN AGE = 52.7 years (range = 30–71 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All participants had breast cancer. The majority of participants had stage 1 or 2 disease. The mean number of days since surgery was 56. All participants were receiving adjuvant chemotherapy.
• OTHER KEY SAMPLE CHARACTERISTICS: 18% had baseline depression 

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

• PHASE OF CARE: Active antitumor treatment

Randomized, controlled trial

• Fatigue Assessment Questionnaire (FAQ)
• European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
• Center for Epidemiologic Studies (CES-D) for depression
• Trail Making Test (TMT)

The overall between-group difference in fatigue was –5.8. This difference was not statistically significant. There was no overall effect of the intervention on the affective or cognitive dimensions in the fatigue measure. In a subgroup analysis of women who were not depressed at baseline, the between-group difference was –8.1 (p = –0.039). Fatigue increased in the relaxation group. Cognitive performance on the TMT improved in the exercise group compared to the control group, but the difference was not significant. Depression remained unchanged in both groups.

The findings of this study show that resistance exercise can be helpful in reducing fatigue during adjuvant chemotherapy, particularly in patients who have depressive symptoms. There were no apparent effects of the resistance exercise program on fatigue or cognitive function.

• Small sample (< 100)
• Risk of bias (no blinding)
• Key sample group differences that could influence results
• Other limitations/explanation: A significantly larger proportion of patients in the exercise group had higher depression scores at baseline (p = 0.0098). This difference may have affected overall findings.

Findings showed that resistance exercise reduced fatigue during adjuvant chemotherapy. These effects were more pronounced in women who did not have depressive symptoms at baseline. This points to the potential influence of depression on fatigue and the efficacy of interventions for fatigue. These results suggest the need to ensure the effective management of depressive symptoms to manage fatigue during treatment. The interventions studied here did not show an effect on depression or cognitive function.

To assess the effects of oral B vitamin complex for the prevention of chemotherapy-induced peripheral neuropathy (CIPN)

Patients newly diagnosed with cancer who were to receive oxaliplatin, taxanes, or vincristine were randomly assigned to receive B complex vitamins or placebo. The intervention was begun about one week prior to the first cycle of chemotherapy and continued for 12 weeks after chemotherapy was completed. Vitamins or placebo were taken twice daily with or after meals. Evaluations were conducted at baseline, after chemotherapy (two to four weeks), and at 12 weeks after completion of chemotherapy.

• N = 50 at three months, 15 at nine months   
• MEDIAN AGE = 53.81 years (experimental), 55.18 years (control)
• AGE RANGE = 29–75 years
• MALES: 33.3%, FEMALES: 66.7%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Varied tumor types; breast and lymphoma were most common.
• OTHER KEY SAMPLE CHARACTERISTICS: Taxanes were the most frequent treatment in the sample.

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

PHASE OF CARE: Active antitumor treatment

Placebo-controlled, blinded, randomized, controlled trial

• Brief Pain Inventory (BPI)
• European Organization for Research and Treatment in Cancer Quality of Life Questionnaire (EORTC QLQ) 
• Patient Neurotoxicity Questionnaire (PNQ)
• Blood assays for B vitamins
• Total neuropathy score (TNS)

No significant differences existed between groups in total neuropathy scores at any time. Significant differences existed between groups in PNQ results at baseline (for motor) and at 12, 24, and 36 weeks for sensory items (p < 0.05). Blood tests showed that B vitamin supplementation increased levels of thiamine, pyridoxine, cobalamin, and folate compared to placebo.

This study did not provide clear evidence regarding the potential role of B vitamin supplementation for the prevention of chemotherapy-induced neuroxicity.

• Small sample (< 100)
• Measurement validity/reliability questionable
• Subject withdrawals ≥ 10%  
• Assessment tools for CIPN have questionable validity and clinical utility.
• The study was underpowered.

The aim of this study was to assess the prophylactic use of B vitamin supplementation; however, the study sample was insufficient to provide a valid assessment.

To review prospective comparative studies that address infection prevention for high-risk patients undergoing chemotherapy and stem cell transplant recipients to evaluate the evidence for best practice and assess for mortality.

Databases searched were CENTRAL (the Cochrane Library issue 4, 2006), PubMed (1966–2008), and LILACS (1982–2006). Unpublished trials that were presented at the following conferences were also queried: American Society of Hematology (2001–2006), American Society of Clinical Oncology (1995–2006), and European Society for Medical Oncology (2002–2006). The references lists from all included studies were reviewed to identify additional studies. 

Keywords searched were not provided by the authors.

Studies were included if they 

• Were prospective comparative studies that included patients with cancer in the hospital or outpatients who were receiving chemotherapy for solid tumors.
• Reported hematological malignancies.
• Reported stem cell transplant recipients.  
• Compared an intervention to placebo, no treatment, or another intervention, as well as all environmental measures, barrier precautions, and other nonpharmacological measures used for the prevention of infectious diseases.

Studies were excluded if they were nonrandomized studies that compared patients with different types of cancer or compared different treatment protocols (i.e. stem cell transplant versus chemotherapy) or if they assessed pharmacological interventions, such as antimicrobial prophylaxis and mouth rinse preparations, unless these interventions were applied together or as a control for the infection-control interventions.

Forty studies were included.

Method of Study Evaluation

Prevention of infection measures used in the studies were identified and grouped together: control of air quality (air filtration), protective isolation, and suppression of the endogenous flora (antibiotics). Subgroup analyses were performed for two major outcomes: all-cause mortality at 100 days and documented infections.

• The total sample size was 40 studies; the sample range across studies was 45 to 3900.
• Twenty-six studies in the analysis studied protective isolation, 11 assessed outpatient versus inpatient care, and three evaluated other random interventions.  
• Twenty-nine studies assessed patients with acute leukemia, six included patients with other hematologic malignancies, and 22 included hematopoietic stem cell transplant (HSCT) recipients exclusively.
• No study included patients with solid tumors at low risk for infection.

The primary outcome, all-cause mortality, was assessed at 30 days, 100 days, and at the longest follow-up reported in each study. Secondary outcomes included the rate and types of infections (including bacteremia), the need for hospitalization and length of hospital stay, the length of the febrile period, infection-related mortality, bacterial and fungal colonization, and antibiotic and antifungal treatment.

• Protective isolation, including control of air quality, barrier isolation, and endogenous suppression due to antibiotics, were shown to significantly reduce mortality (relative risk [RR] = 0.79; 95% confidence interval [CI] [0.72, 0.87]).
• Antibiotic prophylaxis was the main component mediating the beneficial effect of isolation interventions. Improved survival was only shown when antibiotic and antifungal prophylaxis was used with air quality control or barrier isolation (RR = 0.66; 95% CI [0.55, 0.79] in studies with prophylaxis compared with RR = 0.93; 95% CI [0.75, 1.15] in studies without prophylaxis).
• Protective isolation with prophylactic antibiotics also significantly reduced infection, whereas control of air quality or barrier isolation alone did not.
• Control of air quality did not significantly reduce mold infections.  Outpatient mortality was also significantly lower than inpatient mortality (RR = 0.72; 95% CI [0.55, 0.95]).

A combination of air quality control, barrier isolation, and prophylactic antibiotics is estimated to reduce 30-day all-cause mortality by 40% in high-risk cancer patients, including allogeneic or autologous HSCT recipients and patients with acute leukemia. Prophylactic antibiotic use is the most significant preventive strategy; air quality control and barrier isolation did not show an independent contribution, and their use should be reserved for patients at highest risk of infection. Survival significantly improved with outpatient management, which included the use of prophylactic antibiotics without environmental controls.

The reduced mortality seen in outpatient management may be due to

• Selection bias (healthier patients are able to remain outpatient)
• Decreased risk of infection from hospital pathogens
• Use of antibiotic prophylaxis.

There is no evidence that any of these preventive strategies (air quality control, barrier isolation, or prophylactic antibiotics) are necessary or appropriate for low-risk cancer patients with solid tumors.

To evaluate the effectiveness of a three-week educational intervention on patients' levels of fatigue

The intervention was comprised of a printed educational package that contained basic information about fatigue with three face-to-face two-hour sessions once a week that were tailored to the specific needs of the patient groups. The control group received no educational sessions. They did receive standard face-to-face care provided by a healthcare provider in an outpatient clinic. Study measures were obtained at baseline, immediately after the intervention, and at three months.

• N = 160 (81 control group; 79 intervention group)  
• MEAN AGE = 55.3 years (SD = 25–77 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTIC: Early-stage breast cancer 
• OTHER KEY SAMPLE CHARACTERISTICS: Fatigue score was > 2.5 on a 0–10 numeric rating scale. Most subjects were university/college-educated, married/partnered, lived with someone, and were employed.

• SITE: Single-site    
• SETTING TYPE: Outpatient    
• LOCATION: Norway, university-based breast cancer clinic

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

Randomized, controlled trial

• Demographic questionnaire
• Clinical questionnaire
• Numeric rating scale (Fatigue)
• Fatigue Questionnaire (FQ)
• Lee Fatigue Scale (LFS)

This study demonstrated no statistically significant differences between groups or within groups for any fatigue measures.

More research is needed to identify important variables that might affect the experience of fatigue as well as the effectiveness of the type of psychoeducational interventions in women with breast cancer.

A standardized psychoeducational intervention alone may not be sufficient to affect the experience of fatigue among women with breast cancer. Nurses can use the critique of the methods and instruments used and learn about reasons for withdrawing/not completing interventions/evaluations by research subjects to apply to future studies.

RESOURCE TYPE: Evidence-based guideline

PHASE OF CARE: Active antitumor treatment

Recommends a threshold of 10,000 mcl for prophylactic platelet transfusions in patients undergoing therapy for acute leukemia. It is noted that higher levels may be necessary in newborns or patients with signs of hemorrhage and those undergoing invasive procedures. The same threshold is suggested for individuals with solid tumors, except for those receiving aggressive therapy for bladder tumors. In this case, a threshold of 20,000 mcl is recommended. It is suggested that counts of 40,000–50,000 mcl should be sufficient for major invasive procedures in the absence of coagulation abnormality. For minor procedures such as bone marrow biopsy, a platelet level of 20,000 should be adequate for safety.

The overall threshold suggested for most patient situations for prophylactic platelet transfusion is 10,000 mcl.

In areas such as solid tumors, there is limited evidence.

This guideline provides information about administration of platelets for prevention of bleeding and recommended thresholds for prophylactic transfusions.