To determine the feasibility of conducting a randomized, controlled trial to assess the efficacy and safety of modafinil for the treatment of fatigue in patients with lung cancer.

Patients with non-small cell lung cancer (NSCLC) took modafinil in a fixed dose-titration schedule (100 mg daily on day 1 and increasing in the second week to 200 mg daily) for 14 days.

• Twenty patients (6 females, 14 males) were included.
• Median age was 74 years. 
• All patients had NSCLC.

• Multisite
• Inpatient
• United Kingdom

This was an intervention feasibility study.

• Chalder Fatigue Questionnaire (CFQ)
• Epworth Sleepiness Scale (ESS)
• Hospital Anxiety and Depression Scale (HADS)
• Functional Assessment of Cancer Therapy-Fatigue (FACT-F)

• There was a change in fatigue between days 0 and 14.
• Mean fatigue decreased from 6.9 to 3.7.
• There were statistically and clinically significant improvements in fatigue scores from days 0 to 7.
• There was no statistically significant change from days 7 to 14.

It is feasible to conduct randomized, controlled trials.

The study had a small sample size, with less than 30 patients.

• This was an inexpensive pharmacologic intervention for cancer-related fatigue.
• Randomized, controlled trials are needed to confirm the benefit.
• The intervention was well tolerated in patients with advanced cancer.
• Poststudy, 10 patients chose to continue taking modafinil.

To evaluate a multimodal mind-body program (MMMT) compared to walking effect on fatigue in women with stage I–IIIA breast cancer

Participants in the intervention group underwent six hours of training in meditation, whole-food cooking, naturopathic strategies, and mindfulness by a multidisciplinary team. A sports therapist supervised a walking program in weeks 1, 3, and 10. Participants were encouraged to walk at home three times per week for 30 minutes. Participants in the control group also underwent a sports therapist-supervised walking program in weeks 1, 3, and 10. They also were encouraged to walk at home three times per week for 30 minutes.

• N = 55   
• AGE: Control mean: 55.3 years; MMMT mean: 58.1 years
• MALES: 0%, FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Average time first diagnosis: 39.7 months control, 61.9 months MMMT; stage I disease: 48% control, 30% MMMT; stage II disease: 44% control, 56.7% MMMT; stage IIIA disease: 0% control, 6.7% MMMT
• OTHER KEY SAMPLE CHARACTERISTICS: 20% smokers in MMMT group, 0 in control; mean fatigue in last month: MMMT 6.5, control 6.7

• SITE: Single site 
• SETTING TYPE: Outpatient 
• LOCATION: University of Duisburg-Essen, Germany

• PHASE OF CARE: Late effects and survivorship

• RCT

• German Fatigue Assessment Questionnaire with visual analog scale
• European Organization for Research and Treatment of Cancer EORTC QLQ-30
• Multidimensional Fatigue Inventory (MFI)
• Hospital Anxiety and Depression Scale (HADS)
• Menopausal Rating Scale

Unusual fatigue in the last week and last month was improved in both groups with no group differences. Anxiety in the MMMT group was improved compared to the control group (p = .043) during treatment but was not maintained in follow-up (p = .422). Both groups showed overall anxiety improvement. Reported pain between groups was improved in MMMT at follow-up compared to control (p = .031).  Menopausal symptoms decreased in both groups. No significant side effects were seen.

A home-based exercise program showed improvement in reported fatigue. The addition of a mind-body component showed no additional benefit.

• Small sample (< 100)
• Risk of bias (no control group)
• Unintended interventions or applicable interventions not described that would influence results
• Key sample group differences that could influence results
• Questionable protocol fidelity
• Subject withdrawals ≥ 10%

Home-based exercise is a reasonable and safe option for patients experiencing cancer-related fatigue.

To compare regimens using fosaprepitant and olanzapine for chemotherapy-induced nausea and vomiting (CINV) prevention

Patients on regimens for the prevention of CINV who were receiving highly emetogenic chemotherapy (HEC) received either a medication regimen of fosaprepitant, ondansetron, and dexamethasone, or a regimen of olanzapine, ondansetron, and dexamethasone. Those on the olanzapine regimen only received dexamethasone on day 1. Both groups had additional rescue medication as needed. All patients were assessed within 24–72 hours for CINV via follow-up phone calls, with results documented in the electronic medical record.

• N = 148
• MEAN AGE = 58.47 years
• AGE RANGE = 21–81 years
• MALES: 53%, FEMALES: 47%
• CURRENT TREATMENT: Chemotherapy, combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: All were receiving HEC. Tumor types were not reported.
• OTHER KEY SAMPLE CHARACTERISTICS: Of the patients, 38.5% were also receiving radiation therapy.

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

• PHASE OF CARE: Active antitumor treatment

• Retrospective cohort noninferiority design

Complete response defined as no emesis after cycle 1. A difference of 15% complete response (CR) rate was used as the limit for noninferiority testing.

The difference in the CR rate between groups was 8.9% in the acute phase, 12.9% in the delayed phase, and 8.6% overall. Statistical analysis showed that results in the olanzapine group were not inferior based on the difference level specified. Comparison of wholesale acquisition costs showed that the olanzapine regimen was less than 4% of the cost of the regimen using fosaprepitant ($8.58 versus $265.59).

The olanzapine regimen tested here was associated with less than a 15% difference in CR rate compared to a regimen containing fosaprepitant.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement validity/reliability questionable
• How CINV was assessed and documented is not described.
• No subgroup analysis for those receiving concomitant radiation therapy
• No information is provided regarding the use of breakthrough medication and any associated costs.
• No information regarding nausea severity

This study showed that a regimen based on olanzapine was not inferior to one with fosaprepitant among patients receiving HEC if a less than 15% difference in CR rate is clinically acceptable. Individuals on the olanzapine had a higher prevalence of delayed phase CINV, though those in the olanzapine regimen also did not receive dexamethasone after day 1. The fosaprepitant regimen was much more expensive than the olanzapine regimen, so it may be a good alternative for patients with limited coverage or financial resources. Additional studies are needed to identify the most cost-effective regimens for CINV prevention, and this work needs to also provide greater focus on the prevention of nausea.

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.