Randomized after consent to one of three arms (A, B, or C)

A = chlorhexidine mouthwash (0.1% without alcohol, 10 ml) with taste additives

B = placebo mouthwash (normal saline) with taste additives  

C = crushed ice

Participants were stratified according to age (older than 40 versus younger than 40), smoking or nonsmoking, and use of dental prosthesis. Patients and the physician were blinded with respect to mouthwash versus placebo.

Both rinses were administered for 1 minute TID on days 1–21; crushed ice was administered from 10 minutes before until 35 minutes after the start of chemotherapy.

Study sample included patients with gastric or colorectal cancer receiving bolus 5-FU 425 mg/m² and bolus leucovorin 20 mg/m² (Mayo regimen) for five days every four weeks.

Exclusion criteria were head and neck radiotherapy and symptoms of infections.

 
Arm A: n = 73
Arm B: n = 66
Arm C: n = 67

 

Patients were evaluated when they returned for the second round of treatment on day 28.
 
Patients were evaluated on days 14 and 28. Signs and symptoms from the oral cavity were observed and registered on a daily basis and written into the questionnaires on days 14 and 28.

The treating physician evaluated patients on days 14 and 28 using the NCI Common Toxicity Criteria (CTC).
 

No differences were observed in compliance with regimen or side effects (e.g., headache, taste disturbances).
 
Twenty-three percent of patients in arm B and 43% of patients in arms A and C had no mucositis.

Of the three arms, only one patient had grade 4 mucositis (arm A).
The frequency of grades 3 and 4 were 12% in arm A, 32% in arm B, and 10% in arm C. Frequency was significantly lower in arm A (p < 0.01) and arm C (p < 0.005) compared with arm B. Arms A and C were similar.

No differences were observed between patient or physician scoring.

Median duration of oral mucositis was 3 days (arm A), 5 days (arm B), and –1 day (arm C). Duration was significantly shorter in arm B than in arm A (p = 0.035) and arm C (p = 0.003). No differences were observed between arms A and C.

Neither smoking nor performance status predicted severity of oral mucositis.

Ages were unequal across arms but not statistically different.
 

Power analysis of 15%; decreased CTC mucositis grade 3–4; 75 patients in each arm. The study had 225 evaluable participants, but not all participants returned forms.

Two arms were double blinded. Cryotherapy could not be double blinded but was blind to MD assessment.
 

MEDLINE, PsychINFO, and PSYNDEX electronic databases were used, as well as ancestry method using the search terms caregiver or carer or caregiving, intervention or support or training, and elderly or old age. Study statistics that could be converted to effect sizes also were used.

Seventy-eight studies of caregiver interventions in which an intervention condition was compared with a control group were evaluated.

• The sample represented a mixed caregiver population, primarily of patients with dementia (which included older adults with physical disabilities or mental illness), patients who had experienced a stroke, and patients with cancer.
• The mean or median care recipient age was ≥ 60 years.
• Sample sizes in the intervention condition ranged from 4 to 2,268.

Immediate pre- and post-tests on burden were significant. The effect of multicomponent interventions was significantly larger than those of psychoeducation, respite or day care, training of the care recipient, and miscellaneous interventions. The larger the proportion of adult children participating in the intervention, the greater the improvements in burden. Interventions with older caregivers and caregivers with older care recipients yielded larger improvements of burden. Psychotherapy and psychoeducational interventions also were effective in reducing burden. Interventions delivered to individuals were more effective than interventions offered in group sessions. In studies where caregivers provided support for more hours, less improvement in burden was found.

• Multiple dimensions of burden were not disaggregated.
• Many studies had missing data.
• Delivery characteristics were sometimes confounded.
• A selection bias may have existed.
• The study controlled for only some of the possible moderators.
• Efficacy was not evaluated.

To evaluate chlorhexadine prophylaxis for flouruoracil- (5-FU-) based chemotherapy versus normal saline or cryotherapy

The study involved three arms. Arm A received chlorhexidine mouth rinse three times per day for three weeks (n = 70), Arm B received normal saline placebo (n = 64), and Arm C received cryotherapy with crushed ice for 45 minutes during chemotherapy (n = 63).

• The study reported on 225 randomized patients, 206 of which were evaluable.
• All patients had gastrointestinal cancers.

The study was conducted from 2001–2005.

This was a double-blind, placebo-controlled, randomized study, powered for 225 patients (75 in each arm).

The National Cancer Institute (NCI) Common Toxicity Criteria (CTC)  for oral mucositis was used.

Mucositis grade 3–4 occurred more frequently in arm B (33%) than in arm A (13%) (p < 0.01) and arm C (11%) p > 0.005). Duration was significantly longer in arm B than arm A (p = 0.035) and arm C (p = 0.003).

To assess tanezumab as a potential treatment for cancer pain

This is a report of two studies—one was a phase II study and the other was an open-label extension. Patients had an opioid dose adjustment phase of 3–30 days followed by a three-day assessment period. Once opioid management was stabilized, patients were randomized to receive a single dose of 10 mg tanezumab or matching placebo. Between 8 and 16 weeks, patients were given the option to enroll in the extension study. Pain was assessed at weeks 1, 2, 4, 6, 8, 12, and 16. Patients were followed for 40 weeks.

• N = 59 in phase II study, 41 in extension trial   
• MEAN AGE = 58.9 years
• MALES: 46%, FEMALES: 54%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Cancer types were breast, prostate, multiple myeloma, and renal cell cancer. All had pain from bone metastases.
• OTHER KEY SAMPLE CHARACTERISTICS: Baseline worst pain scores were an average of 6.4.

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: Multiple countries

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Palliative care 

• Double-blind, randomized, controlled trial followed by open-label extension

• 11-point numeric pain rating scale
• Brief Pain Inventory (short form)
• Neuropathy Impairment Score (NIS)

No significant differences between groups in average or worst pain scores were reported, although, after week 4, pain was trending lower for the tenazumab group. No significant differences between groups in analgesic consumption existed. Pain began to increase during the extension period. Adverse events were comparable between groups. Six episodes of abnormal peripheral sensation were reported.

This study did not demonstrate a statistically significant difference in pain with tanezumab compared to placebo; however, between weeks 4 and 8, pain was lower with tanezumab.

• Small sample (< 100)
• Unintended interventions or applicable interventions not described that would influence results
• Subject withdrawals
• No information is provided regarding previous use of any bone-modifying agents

Evidence is currently insufficient to show the efficacy of tanezumab for pain from bone metastases. However, lower pain levels shown suggest that additional research in this area is warranted.

To evaluate the effects of guided meditation and music on patients’ anxiety, pain, and fatigue during breast biopsy

Patients were randomly assigned to meditation, music, or standard care with supportive dialogue. Patients in the meditation and music groups were given headphones. During the procedure, patients in the meditation group listened to an audio recorded medication designed to help patients relax and focus on feelings of kindness and compassion. The music group listened to their choice of music. The standard care control group received supportive dialogue during the procedure. Biopsies were done with local anesthesia. Study assessments were done pre and post biopsy.

• N = 121   
• MEAN AGE = 52.96 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Patients undergoing breast biopsy. Of these, 30% had previous breast biopsy.  
• OTHER KEY SAMPLE CHARACTERISTICS: The majority were Caucasian. The average education level was 15 years.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: North Carolina

• PHASE OF CARE: Diagnostic

• Three-group, randomized, controlled trial

• State-Trait Anxiety Inventory (STAI)
• Numeric pain scale (0–10)
• Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F)
• Questionnaire on the Quality of Physician-Patient Interaction (QQPPI)
• 11-point numeric scale to assess engagement in the study interventions

Anxiety declined in all groups, while those in the meditation group (p = 0.04) and the music group (p = 0.03) had greater decline in anxiety compared to controls. Fatigue declined in all, with no significant differences between groups. Decline in pain differed among the study groups. The music group had greater increases in pain than the meditation group (p = 0.03), and pain increased in the control group. No difference in pain scores existed between the music and control groups. Overall post-procedure pain scores averaged 1.8.

The study findings suggest that a meditation intervention during biopsy may help to reduce patient anxiety and pain.

• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Very low pain scores suggest floor effects in measurement.
• Single point in time measurement of anxiety post-procedure—does not determine longer term effects on anxiety

This study showed that listening to a meditation intervention during breast biopsy was associated with lower anxiety postprocedure. This is a low-risk intervention that may be helpful for patients; however, whether this effect would have lasted for any length of time after the procedure is unknown.

To evaluate the evidence supporting the use of palifermin for its approved indication in patients undergoing hematopoietic stem cell transplantation (HSCT) for hematologic maligancies, and for other populations at risk of oral mucositis

• Databases searched were MEDLINEand PubMed. Also, meeting abstracts for American Society of Clinical Oncology (ASCO) and American Society for Therapeutic Radiology and Oncology (ASTRO) were searched using the keywords mucositis and palifermin.
• Search keywords were oral mucositis, palifermin, and keratinocyte growth factor (KGF).
• Studies were included if they involved only human clinical trials.
• Studies were excluded if they were reviews or preclinical studies.

A total of 100 papers and four abstracts were retrieved. Full papers were used. Studies with level 2 or higher clinical evidence, studies that were not randomized clinical trials (RCTs), case reports, and economic evidence also were used.

• A total of 12 papers and three abstracts were included in the final review.
• The review did not discuss the samples.
• Patients had hematologic malignancies and planned to receive conditioning regimen for an autologous or allogenic HSCT, cycled chemotherapy for the treatment of solid tumors, or radiation therapy with concomitant chemotherapy for the treatment of cancers of the head and neck.

The evidence review supported palefermin use in the amelioration of oral mucositis. Palifermin was associated with a reduced need for opioid analgesics, reduced risk of febrile neutropenia, reduced need for total parenteral nutrition (TPN), improved patient‐reported function, and reduced hospital stay. In addition, palifermin was associated with a decrease in the costs of mucositis-associated complications in autologus HSCT recepients. It must be noted that the this was not a decrease in costs associated with mucositis‐associated complications, but a decrease in costs because of the lower incidence of adverse outcomes in patients treated with palifermin.

Palefermin is effective in the treatment of mucositis and the need to receive mucotoxic conditioning regimens in preparation for HSCT.

RCTs are needed to investigate the benefits of palifermin in patients who are not diagnosed with head and neck cancer, as the risk of significant mucositis is unpredictable in these patients. Also, concerns exist that palifermin has the potential to stimulate primary or secondary tumor growth.

To compare the use of a three-drug antiemetic regimen to a two-drug antiemetic regimen in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with non-Hodgkin lymphoma receiving R-CEOP or CEOP, highly emetogenic regimens (HECs)

• N = 108 enrolled, 90 completed the study.  
• AGE = 40.4 years
• MALES: 68.5%, FEMALES: 31.4%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Non-Hodgkin lymphoma
• OTHER KEY SAMPLE CHARACTERISTICS: Treatment with R-CEOP or CEOP

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

PHASE OF CARE: Active antitumor treatment

Prospective, open-label, randomized, comparative clinical trial

• Diaries–patient self-report
• CTCAE, version 4, for vomiting and retching
• VAS for nausea
• FLI-E questionnaires for quality of life

Complete response (CR) was defined as no emesis and no use of rescue medications. 

• Overall study CR: Aprepitant group 77%, control group 56% (p = 0.03)
• CR acute phase: Aprepitant group 92%, control 78% (p = 0.045)
• CR delayed phase: Aprepitant group 82%, control 64% (p = 0.037)
•  Secondary end point–no emesis:  
• Acute phase: Aprepitant group 94%, control 84% (p = 0.153)
• Delayed phase: Aprepitant group 86%, control 64% (p = 0.003)
• Overall study: Aprepitant group 78%, control 60% (p = 0.02)
• No differences for nausea in the acute phase and overall phase between the groups
• In the delayed phase, 73% of the aprepitant group reported no nausea and 50% of the control group (p = 0.2).
• FLI-E scores for CINV with minimal or no effect on quality of life: Aprepitant group 84%, control 64% (p = 0.02)

CR rate was achieved significantly with the addition of aprepitant to a two-drug antiemetic in both the acute and delayed phases. There were significant differences related to no emesis between the groups but no differences in nausea. For patients taking aprepitant, CINV had less affect on quality of life throughout treatment.

• Small sample (< 100)
• Risk of bias (no blinding)

For patients receiving R-CEOP or CEOP for non-Hodgkin lymphoma, a three-drug regimen was more effective in preventing CINV  than a two-drug regimen and was generally well-tolerated.

STUDY PURPOSE: To evaluate the effectiveness and safety of ramosetron for chemotherapy-induced nausea and vomiting (CINV) through a systematic review of randomized, controlled trials (RCTs)

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 16
• TOTAL PATIENTS INCLUDED IN REVIEW = 2,083
• SAMPLE RANGE ACROSS STUDIES: Variety of ages and diagnoses
• KEY SAMPLE CHARACTERISTICS: Most cisplatin-based regimens in China, Japan, Taiwan, India, and Korea

PHASE OF CARE: Active antitumor treatment

In the acute phase, ramosetron significantly reduced nausea and acute vomiting compared to other 5HT3RAs. In the delayed phase, difference in complete response of nausea existed between ramosetron and other 5-HT3RAs. No significant differences existed between common adverse reactions.

The study concluded that ramosetron for CINV may be as effective and as tolerable as other 5-HT3RAs, but more well-designed RCTs are needed to confirm the effect of ramosetron on acute or delayed CINV in patients with cancer.

The methodological quality of studies was not high (different dosages, missing data, limited information on MEC or low risk).

Ramosetron may be effective for CINV and as tolerable as other 5HT3RAs. More well-designed RCTs are needed to confirm the effect of ramosetron on acute or delayed CINV.

To investigate whether the use of honey provides protection from the effects of radiation-induced mucositis

Databases searched were PubMed, MEDLINE via OVID, EMBASE, CINAHAL via EBSCO, and Cochrane.

Keywords searched were honey and mucositis or stomatitis.

Studies were included in the review if they

• Were randomized controlled trials that investigated protective effects of honey in patients with head and neck cancer undergoing radiation therapy.
• Used Radiation Therapy Oncology Group (RTOG) or World Health Organization (WHO) criteria to evaluate the severity of radiation mucositis.

Studies were excluded if they

• Were nonhuman clinical trials.
• Were nonrandomized controlled trials.
• Involved patients without diagnoses of head and neck cancer.
• Were trials in which the protective effects of honey were not studied.

A total of 15 references were retrieved. Four trials reported on the protective effects of honey. One of these was nonblinded. The remaining three were randomized examiner-blinded, and these three trials were assessed for overall risk of bias using the Cochrane method. Three of the four studies met the inclusion and exclusion criteria for the meta-analysis.

• The final number of studies included was four human trials, but one trial was excluded because it reported only on pain relief, not the protective effects of honey.   
• The total sample across all studies was 120 patients with 40 in each study.
• Studies involved adults with head and neck cancer receiving radiation therapy. In one study, patients were receiving concurrent chemotherapy and radiation. I all studies, patients with systemic illness or prior chemotherapy were excluded.

All patients were undergoing the active treatment phase of care.

Meta-analysis of the of the three trials reported that honey appeared to have protective effects against radiation-induced mucositis by 80% compared to the control group. Overall relative risk of developing mucositis was almost 80% lower (risk ratio, 0.19; 95% confidence interval, 0.098–0.371) in the honey treatment group than in the control group.

Trials were fairly homogeneous (I² = 0%, p = 0.39), so meta-analysis used a fixed-effects model (Mantel-Haenszel method) to calculate a pooled risk ratio.

• A limited number of trials met the criteria for meta-analysis. Individual studies were weak.
• Two of the studies included had a high risk of bias because of plausible bias in several criteria.
• Patients were not blinded because of the taste of honey. 
• Grade 3 or 4 on the RTOG scale was used as the outcome measure of interest.

Further research is needed to strengthen the current evidence prior to any clinical recommendations for practice. They suggested blinding the assessor in future studies.

The purpose of the study was to Investigate efficacy of secondary antifungal prophylaxis (SAP) .  

Primary antifungal prophylaxis was fluconazole 200 mg PO daily. Patients with documented IFI were treated with intensive antifungal therapy. Two of these had complete response prior to futher treatment of primary disease. Thirty-three patients received prophylaxis with voriconazole, 21 received itraconazole, two received micafungin, and one received amphotericin B. The antifungal prophylaxis continued through time of neutropenia and ended when eradication of residual diseases or initiation of salvage therapy due to failure of SAP.

• 57 patients were included.
• 149 cycles of therapy
• Ages ranged from 14-77 years
• 56% were male, 44% were female
• 21 patients had AML, 23 had ALL, 2 had NHL, and 1 patient had MDS-RAEB
• 70% were in complete remission, 30% identified as uncontrolled disease.
• Medical records for all patients hospitalized for more than two weeks were reviewed.
• 57 patients who received 149 cycles of therapy were included.
   

• Single site  
• Inpatient stem cell transplantation center  
• Tianjin, China
   

Active treatment (i.e., chemotherapy or stem cell transplantation)

Retrospective chart review

• Diagnosis of IFI was according to revised EORTC/MSG criteria: proven cases diagnosed according to pathologic or microbiological evidence.  Probably and possible cases documented by radiological and/or microbiological evidence.
• Response to antifungal treatment graded according to criteria defined by complete response (CR), pratical response (PR), stable disease (SD), or progressive disease (PD).
• Relapse defined as recurrence of fungal lesions in historical foci.
• Breakthrough infection defined as emergence of fungal lesions in other than historical foci.

Median follow-up 120 days (12–1,080) revealed 11 failures of SAP, representing 7.4 per 100 cycles of therapy and cumulative incidence of 24.5% at end of follow-up. Four experienced infection progression, three had infection recurrence, and the other four had breakthrough infection. Of the 11 failures, five occurred in the allo-HSCT and six during chemotherapy. High-dose steroids and neutropenia of more than 14 days were identified as risk factors for SAP failure.

SAP demonstrated high efficacy and can protect further chemotherapy and SCT. Two risk factors, high-dose steroids and neutropenia longer than 14 days, were identified as factors of prophylaxis failure and these patients were deemed to require special consideration.

• Small sample size
• Retrospective study design
   

Based on small sample size and study design, evidence is weak in recommendation for practice.