To investigate the impact of dietary counseling or nutritional supplements on morbidity and quality-of-life outcomes in patients with cancer during and three months after radiotherapy (RT)

Group 1 patients received individualized dietary counseling based on regular food groups. Group 2 patients consumed two cans of a high-protein liquid supplement per day in addition to their usual diet. Group 3 patients (control) were instructed to maintain their ad lib intake.

This prospective study design allowed for comparison of the effects of the interventions across the study arms over time. Evaluation took place at three points: baseline, at the end of RT, and three months later. Several types of outcome variables were measured, including nutritional status indicators.

• The study evaluated 111 patients with colorectal cancer referred for preoperative radiotherapy plus 5-fluorouracil//folinic acid administered on the first and last five days.
• The sample included 66 males and 45 females.
• Patient age range was 32–88 years.
• Patients were stratified by cancer stage and then randomized (n = 37 in groups 1, 2, and 3).
• All patients completed the study.

• Single radiation oncology department
• Lisbon, Portugal

The study was a prospective, randomized, controlled trial.

• Nutritional assessment
• Patient-Generated Subjective Global Assessment: to assess symptoms, weight change, alterations in food intake, functional capacity, components of metabolic stress, and physical examination findings
• Anthropometrics: height and weight
• Nutritional requirements and dietary assessment
• World Health Organization formulas
• Diet history: 24-hour food questionnaire
• European Organization for Research and Treatment Cancer Quality of Life questionnaire (EORTC QLQ-C30)

Protein 3 energy intake: at three-month time point, group 1 maintained nutritional intake and groups 2 and 3 returned to baseline. After RT and at three months, rates of anorexia, nausea and vomiting, and diarrhea were higher in group 3. At RT completion, 211 QOL function scores improved in group 1, 3 out of 6 function scores improved in group 2, and all scores worsened in group 3.

Researchers concluded that both interventions positively influenced outcomes. Three months after RT, dietary counseling was the only intervention to sustain a significant impact on patient outcomes.

• The study was limited to patients with colorectal cancer.
• The sample was of mixed disease stage (45 were stage I/II, 66 were stage III/IV), although patients were stratified for this.
• Measurement of outcomes was complicated by the fact that patients were receiving active treatments with RT.
• This type of dietary intervention is available to patients by referral to a registered dietitian. Expertise is required, which may be cost-prohibitive or not available at various settings.

This study examined the effects of individualized dietary counseling in a high-risk group. Whether individualized dietary counseling in other cancer groups will produce the desired outcome of increased appetite needs to be examined.

To determine the effect of daily bathing with chlorhexidine on nosocomial infection rates

Nosocomial infection rates were compared before and after the implementation of a daily chlorhexidine bathing. A solution of 4% chlorhexidine gluconate was diluted in 10 parts water to 1 part cleanser and was used to rinse all body surfaces except the face.

• N = 330
• AGE RANGE = 0–21 years
• MALES: 54.9%, FEMALES: 45.2%
• KEY DISEASE CHARACTERISTICS: Multiple tumor types
• OTHER KEY SAMPLE CHARACTERISTICS: Individuals with fever on admission were excluded from the analysis.

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

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Pediatrics

• Retrospective cohort comparison

• Infections were recorded based on the presence of a fever for more than 24 hours and/or the presence of positive cultures in bodily fluid.
• The presence of a fever with no positive cultures was considered presumed infection.
• The infection rate was quantified as incidence density per 100 days.

The infection rate was lower in the study group compared to historical controls only in those aged 12–21 years (p = 0.008). This age group also showed a higher prevalence of neutropenia (p = 0.039) in the study group. Overall, no significant differences existed in infection rates between study groups.

The results did not show an overall reduction in infections with daily chlorhexidine bathing, although some benefit was seen among older adult patients.

• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Differences in the rate of neutropenia between study cohorts existed.

The findings did not provide definitive evidence that daily chlorhexidine bathing reduces hospital-acquired infections; however, the rates among older adult patients, who also had a higher prevalence of neutropenia, improved. Chlorhexidine bathing is a simple and potentially low cost intervention that may have some benefit for neutropenic patients. Further research in this intervention is warranted.

To evaluate the effect of sublingual fentanyl on breakthrough cancer pain in opioid-tolerant patients; to assess how well patients tolerate sublingual fentanyl

The study included an open-label titration phase, a two-week double-blind efficacy phase, and a long-term open-label safety phase of up to 12 months duration. Sublingual orally disintegrating tablet (ODT) fentanyl was given at 100 mcg and titrated in the open-label phase to a maximum dose of 800 mcg until patients identified a single effective and tolerable dose. In the double-blind phase, patients received seven doses of the study drug and three doses of placebo. The study drug and placebo were identical in appearance. Patients took doses in a randomly assigned sequence. Rescue medication could be administered if needed after two hours. Patients were followed on a daily basis by telephone to monitor use of the study and rescue medications and the incidence of adverse events during the titration phase. Thereafter, investigators monitored patients in person on a monthly basis and at two weeks after monthly by-telephone evaluations. Patients maintained an electronic daily diary. Pain intensity  and pain relief were recorded immediately prior to treatment and at 10, 15, 30, and 60 minutes after use.

• The sample was composed of 66 patients in the double-blind phase and 72 in the long-term phase.
• Mean patient age was 55 years (SD = 11.5 years). Age range was 21–80 years.
• Of all patients, 45.8% were male and 54.2% were female.
• Authors did not report specific diagnoses.
• Of all patients, 84% were Caucasian.

• Multisite
• Outpatient

• Phases of care: end of life, palliative care
• Clinical applications: late effects and survivorship

Randomized placebo-controlled phase III trial

• Eleven-point verbal rating scale, to measure pain severity
• Five-point verbal scale, to measure pain relief
• Patient Global Evaluation of Medication
• Evaluation of adverse events by clinicians

Overall, patients received the study drug for an average of 51 days. Median dose of ODT fentanyl was 600 mcg. A median of three doses were taken per day. The most common treatment-related complications were nausea (12.2%), vomiting (5.3%), and somnolence (4.6%). One patient developed stomatitis, which may have been related to the study drug. Sublingual ODT fentanyl was significantly more effective (p < 0.006) than placebo at all time points and was most effective at 60 minutes (p = 0.0004). Pain relief was significantly better with ODT fentanyl than with placebo (p = 0.0007) at 15 minutes after use and at 30 and 60 minutes.

Sublingual ODT fentanyl was effective in the management of breakthrough pain, and patients tolerated the medication well.

• The study had a small sample, with fewer than 100 patients.
• Authors did not discuss the use of rescue medications.
• Authors provided no information about baseline pain levels. Duration or diagnosis was provided to determine generalizability of findings.  No information is provided regarding background pain management or total opiod doses. The follow-up period was relatively short, and a large number of cases were lost to follow-up.

In this study ODT fentanyl was effective in treating breakthrough pain; therefore, ODT fentanyl may be an appropriate means to manage this problem. The study reported one case of stomatitis, which may have been related to this drug. Nurses should be aware of the potential of stomatitis occurring with a patient's use of ODT fentanyl. The follow-up period in the present study was relatively short. Longer use of ODT fentanyl may pose greater risk of stomatitis.

To assess the efficacy of and determine the side effects related to the use of sublingual fentanyl spray for the treatment of breakthrough cancer pain  

The study involved an open-label titration period followed by a treatment period of up to 26 days. The primary efficacy measures were  summed pain intensity difference at 30 minutes (SPID₃₀), total pain relief at 30 minutes (TOTPAR₃₀), and patient global evaluation of medication study at 30 minutes. Efficacy was observed 5–60 minutes postdose and for side effects throughout. Patients were randomly assigned to the study drug or placebo. After the treatment period, a follow-up assessment was done 30 days after treatments. The fentanyl sublingual spray was titrated from 100 mcg to up to 1600 mcg until an effective dose was reached. Rescue medication was the medication the patient had for breakthrough pain before the study.

• The sample was composed of 130 patients, 98 in the placebo-controlled period. The final assessment was based on 90 patients.
• Mean patient age was 65 years.
• Of all patients, 46.9% were male and 53.1% were female.
• All patients had 1–4 episodes of breakthrough pain daily, which was partially controlled by means of at least five morphine equivalents of opioid.
• The most common cancers in the sample were breast, skin, lung, and head and neck cancers.

• Single site
• Inpatient and outpatient
• Center for Clinical Research, Winston-Salem, North Carolina, United States

• End-of-life care
• Clinical applications: end-of-life and palliative care, elderly care
   

Randomized, double-blind, placebo-controlled study 

• Summed pain intensity difference at 30 minutes (SPID₃₀)
• Total pain relief at 30 minutes (TOTPAR₃₀)

Of 130 patients, 98 entered the double-blind period. Relative to placebo, fentanyl sublingual spray significantly improved mean SPID scores from 5 minutes (p = 0.0219) through 60 minutes (p < 0.0001), including the primary endpoint at 30 minutes (p < 0.0001). The most frequent effective dose was 800 mcg. Side effects reported were nausea, hyperhidrosis, and peripheral edema; however, investigators did not consider any of these effects to be related to the treatment. Side effects occurred in about 4% of patients. Degree of pain relief and speed of pain relief were significantly higher with the study drug (p < 0.0001).

In this study fentanyl sublingual spray was well tolerated and effective in treating breakthrough of cancer pain.

Proper patient assessment prior to recommendation of the treatment is highly important. Oral hygiene is important during treatment with fentanyl spray. Keep an eye on side effects to ensure the comfort of the patient.

To evaluate the efficacy of fentanyl buccal soluble film (FBSF), at doses of 200–1200 mcg, in the management of breakthrough pain (BTP) in patients with cancer who are receiving ongoing opioid therapy

In phase 1, patients were screened, for up to one week, to assess tolerance of FBSF. In phrase 2, the titration phase, patients started with 200 mcg dose that was increased in a stepwise fashion (200, 400, 600, 800, 1200 mcg) until the patient experienced pain relief. Patients were discontinued from the study if a satisfactory dose could not be determined. If a satisfactory dose was achieved for two BTP episodes, patients proceeded to the double-blind phase. The double-blind phase lasted up to two weeks. Each patient received nine doses of FBSF (six of study medication and three of placebo). A computer determined the order of administration. Patients were allowed to use usual rescue medication if they did not receive adequate pain relief in 30 minutes. Study medication was allowed every four hours.

• The safety population consisted of 151 patients; 82 patients were in the efficacy population (double-blind phase).
• The study comprised 394 FBSF-treated episodes and 197 placebo-treated episodes.
• In the safety population, mean patient age was 57.1 years. In the efficacy population, mean patient age was 56.8 years.
• In the safety population, 56% were female and 44% were male. In the efficacy population, 55% were female and 45% were male.
• In regard to diagnosis, the conditions that follow were represented in the sample at the cited percentages: breast cancer, 23%; lung cancer, 17%; colorectal cancer, 11%; gastroesophageal cancer, 7%; pancreatic cancer, 6%; head and neck cancer, 5%; nociceptive pain, 50%; neuropathic pain, 32.5%.

• Multisite
• Outpatient
• Thirty centers in the United States

Randomized placebo-controlled, double-blind, multiple-crossover study

• A 0–10 scale (0 = no pain, 10 = worst pain), to measure pain intensity (PI)
• A 0–4 scale (0 = no relief, 4 = complete relief), to measure pain relief
• A measure of pain intensity difference (PID): baseline pain intensity – pain intensity at assessment point
• The sum of pain intensity difference (SPID): sum of PI differences 30 minutes postdose
• A five-point scale of global satisfaction (poor–excellent), with measures taken at the time of rescue-drug administration and 60 minutes postadministration of study drug
• LSM (least-squares mean) ± SEM (standard error mean) = outcome

• For both groups, PI baseline mean was 6.9 and median was 7.0.
• LSM was greater for FBSF-treated episodes than for placebo-treated episodes (47.9 ± 3.9 versus 38.1 ± 4.3) (p = 0.004).
• Results revealed statistically significant separation from placebo at 15 minutes postdose (p < 0.05) through 60 minutes postdose [the last time point assessed (p < 0.001)].
• PID values for FBSF-treated episodes were greater at all time points and significant at 30 minutes (p < 0.01) through last assessment (p < 0.01).
• The percentage of episodes with 33% or 50% decrease in pain was significant compared to the percentage of those episodes related to placebo.
• Satisfaction was greater with FBSF compared to placebo (mean 2.0 versus 1.5, respectively; p < 0.001).
• Mean (± SEM) number of episodes when rescue medication was used was significantly lower after treatment with FBSF than with placebo (30% ± 3.5% versus 44.6% ± 4.4%, p = 0.002).
• Twenty-three patients, or 15.2%, experienced serious adverse events, but according to investigators no event was related to the study drug. Treatment-related adverse events in the titration phase included the conditions that follow, at the cited percentages of patients affected: nausea, 9%; vomiting, 9.3%; somnolence, 6%; dizziness, 4.6%; headache, 4%. Adverse events in the double-blind phase phase included the conditions that follow, at the cited percentages of patients affected: nausea, 9.9%; vomiting, 9.9%; headache, 1.2%.
• Overall satisfaction was higher for FBSF, although a placebo effect did exist (67.1% for FBSF and 47.1% for placebo).

FBSF was more effective than placebo for the treatment of breakthrough pain in patients with cancer. The treatment was well tolerated.

• The study had a small sample, with fewer than 100 participants.
• Not all patients completed all measures.

FBSF shows favorable and safe results for the treatment of breakthrough pain, but the treatment remains investigational.

To examine the effects of inpatient and outpatient rehabilitation (i.e., physical therapy, psycho-oncological treatment, patient education, medical treatment, group sessions) on quality of life and psychosocial outcomes

Patients who had radical prostatectomy participated in inpatient and/or outpatient rehabilitation within 14 days after completion of acute oncology treatment

• N = 714   
• AGE = 57 years (SD = 4.4)
• MALES: 100%  
• KEY DISEASE CHARACTERISTICS: Prostate cancer stages T1–4, pN0, M0; average KPS 79 (SD = 8.7)
• OTHER KEY SAMPLE CHARACTERISTICS: Patient who had radical prostatectomy aged 18–64 years and were employed. Excluded those with excessive psychological or physical distress or cognitive limitations as assessed by rehabilitation physicians, those who were unable to speak and read German, and those who were diagnosed with a second cancer requiring treatment.

• SITE: Multi-site   
• SETTING TYPE: Multiple settings    
• LOCATION: Four clinics in Germany

PHASE OF CARE: Transition phase after active treatment

• Quasiexperimental repeated measures design with convenience sampling from inpatient and outpatient treatment areas
• No blinding

• European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ)-C30: Two items for subjective cognitive function
• EORTC QLQ-Prostate-specific 25 (PR25)
• Hospital Anxiety and Depression Scale (HADS)

Subjects reported similar cognitive function scores at baseline and one year after rehabilitation. Cohen’s d  was 0.51 and 0.54 respectively (both p < 0.001). They reported higher cognitive function at the end of rehabilitation (F [df 1.8, 1238.2] = 138.1, p < 0.001). Quality of life was higher at a one-year follow-up (p < 0.001). Anxiety was lower at the end of rehabilitation for inpatient and outpatient rehabilitation groups (p < 0.001). Depression was lower at end of rehabilitation and sustained at a one-year follow-up (p = 0.008).

The effect of structured rehabilitation on outcomes in this study was unclear, and no clear differences in outcomes based on whether patients received inpatient or outpatient rehab services were observed.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Risk of bias (no appropriate attentional control condition)  
• Risk of bias (sample characteristics)
• Unintended interventions or applicable interventions not described that would influence results
• Intervention expensive, impractical, or training needs
• Subjective cognitive function measure was limited; objective measures of cognitive function were not used.  
• Because rehabilitation was given as part of standard medical care, many other factors could have influenced the results.

Rehabilitation, whether provided in an inpatient or outpatient setting, improved patients’ perception of quality of life, depression, anxiety, and cognitive function by the end of rehabilitation. Perceived improvements in quality of life and depression persisted at one year after treatment.

To evaluate the role of benzydamine in the prevention of mucositis in patients receiving more than 50 Gy of radiation therapy

Patients were stratified according to receiving radiotherapy or radiotherapy and chemotherapy, and then randomly assigned to control or treatment with benzydamine. All patients were advised to use saline mouth rinses, and those in the treatment group also used 0.15% benzydamine hydrochloride rinse. Both groups were to rinse and gargle with the mixture four to six times daily. Patients were examined weekly until four weeks after completion of the treatment.

• N = 120   
• AGE RANGE = 19–90 years
• MALES: 87.5%, FEMALES: 12.5%
• CURRENT TREATMENT: Radiation, combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: All had head and neck cancer.
• OTHER KEY SAMPLE CHARACTERISTICS: Radiotherapy dosages ranged from 56–70 Gy.

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

PHASE OF CARE: Active antitumor treatment

Randomized, controlled trial

• Common Terminology Criteria for Adverse Events (CTCAE) toxicity, version 4
• World Health Organization (WHO) mucositis grading scales

Patients receiving radiotherapy alone who used benzydamine had a lower prevalence of grade 3 mucositis compared to controls (p = 0.038); however, control patients receiving only radiotherapy also had a longer duration of radiation treatment (p = 0.042, 56 versus 44 days). No significant difference in mucositis outcomes occurred among those receiving both chemotherapy and radiation. Control patients in this group had a longer duration of radiation therapy.

Benzydamine prophylaxis appears to be effective to reduce the severity of oral mucositis among patients receiving radiotherapy alone for head and neck cancer. Effects for patients receiving both chemotherapy and radiation therapy were not seen.

• Baseline sample/group differences of import
• Risk of bias (no blinding)
• Measurement/methods not well described
• Exact measure used in analysis and timing of measurement used not stated
• In both treatment types, patients in the control group had a significantly longer duration of radiation therapy.

Oral rinses with benzydamine were helpful to reduce the prevalence of severe mucositis among patients receiving radiation therapy for head and neck cancer. It is unclear if benzydamine can also be helpful for patients receiving combination chemotherapy and radiation therapy.

To determine if oral melatonin administered at night would reduce fatigue and improve sleep in patients with advanced cancer treated in a palliative care facility

This was a two-part trial. In part one, patients received either melatonin (20 mg) or placebo followed by a washout of two days, then crossed over and received the opposite of the first week of treatment. Part two was an open-label study of patients who completed part one and chose to continue melatonin. Study questionnaires were completed at the beginning and end of each treatment period (days 1, 7 ,10, and 17). In part two, study measures were obtained weekly. Patients were randomly assigned to the order in which they received melatonin or placebo.

• N = 34 by ITT analysis  
• MEAN AGE = 64.5 years
• AGE RANGE = 35–84 years
• MALES: 38%, FEMALES: 62%
• KEY DISEASE CHARACTERISTICS: Breast and lung cancer were most common. All had advanced disease.

• SITE: Single site  
• SETTING TYPE: Inpatient  
• LOCATION: Denmark

• PHASE OF CARE: Active antitumor treatment

• Randomized, placebo-controlled, crossover trial

• Multidimensional Fatigue Inventory (MFI)
• EORTC Cancer Quality of Life Core 15 for palliative care patients (EORTC-QLQ-C15-PAL)

No significant differences were noted in patient outcomes between the placebo and melatonin groups.

Melatonin administration did not improve fatigue, insomnia, or other symptoms in patients with advanced cancer.

• Small sample (less than 100)
• Subject withdrawals 10% or greater
• Multiple and frequent use of the same measurement tools

This study did not show any improvement in fatigue or sleep as a result of melatonin.

Patients smeared 20 mL of pure, natural honey (acidic with a pH of about 3.9) on the inside of their mouths 15 minutes before, 15 minutes after, and six hours after radiation. Patients rinsed honey on oral mucosa and then swallowed it slowly. Patients were randomized to the treatment or control group. Patients also used benzydamine HCL plus supportive oral care measures. A solubility-reducing factor present in honey can activate in the absence of saliva.

• N (experimental group) = 20
• N (control group) = 20
• KEY DISEASE CHARACTERISTICS: Patients with head and neck cancer receiving chemotherapy and radiotherapy
• OTHER KEY SAMPLE CHARACTERISTICS: Radiation dose of 60–66 Gy; chemotherapy: cisplatin 20 mg/m² once a week before radiotherapy

• April 2005–July 2006

• World Health Organization

• Treatment group: No patients developed grade 4 mucositis, and only three (15%) developed grade 3 mucositis.
• Control group: Three patients (15%) developed grade 4 mucositis, and nine (45%) developed grade 3 mucositis.
• Stated as significant, but value not given
• Five patients in the control group had therapy interrupted.
   

• Small sample
• Did not give p values for differences in mucositis
   

• Easy to use
• Cost-effective
• Pleasant

This trial randomized patients to two arms: one group received fluoxetine, and the other group received placebo for five weeks.

Patients with cancer (N = 115) were randomized to two arms: fluoxetine treatment (n = 45) versus placebo (n = 46) for five weeks.

A randomized, controlled, double-blinded trial design was used.

• Hospital Anxiety and Depression Scale (HADS)
• Symptom Checklist–90–Revised (SCL90-R)
• Montgomery-Åsberg Depression Rating Scale (MADRS)
• Hamilton Anxiety Scale (HAS)
• Spitzer Quality of Life Index (SQOLI)

Response rate (HADS) score < 8 after five weeks was not significantly higher in the fluoxetine group compared to the placebo group. There was significant decrease in mean scores on the SCL90-R in the fluoxetine group. There was no difference between groups on MADRS, HAS, or SQOLI.

Lower scores on subscales of the SQL90-R may reflect changes in anxiety levels between groups.

The authors did not mention power of effect size.