GM-CSF 2 mcg/kg (-1) (150 mcg) daily for 14 days starting on day 14 of a 21-day course of RT.

Note: Placebo injections were not given; observer was blinded to treatment.

The study was comprised of 29 patients (GM-CSF = 14).

Power analysis was completed, but not met (n = 17 in each group).

Patients with proven T1 N0 or T2 N0 glottic carcinoma were being treated with radiotherapy using a 16 fraction 3-week regimen.

Required to have a WHO performance status of grade 0 or higher, no renal or hepatic issues, serious infections requiring antibiotics, or likely need for corticosteroids.
 

Prospective, randomized, observer blind phase II trial

• RTOG
• Skin erythema
• Moist and dry desquamation
• Pain on swallowing
• Severity of dysphagia
• Analgesic usage
• Evidence of candida infection and laryngeal edema
• Patients weights before and after treatment
   

Significant difference in the incidence of mucositis p < 0.05, mean time of healing improved but not significant p = 0.25.
No differences in dysphagia, odynophagia, analgesic use, candida infection, of laryngeal edema.
 

• Study sample size was very small.
• Only used for early treatment of laryngeal cancer with radiotherapy using 16 fraction 3-week regimen.
• Frequent side effects related to GMCSF
• No large trials have been conducted.
   

Subcutaneous (SC) morphine 5 mg or placebo in opioid-naïve patients and regular oral morphine dose plus half of the every-four-hour (q4h) dose given SC in patients on regularly scheduled opioids

• The sample was comprised of nine patients (seven opioid naïve and two opioid tolerant).
• Mean patient age was 73 years.
• The sample included four women with advanced cancer and dyspnea resulting from lung involvement.
• All patients had normal Mini-Mental Status Examinations (MMSEs).

The study was conducted in an inpatient geriatric hospital.

The study was a double-blind, placebo controlled, randomized, cross-over trial.

• Dyspnea visual analogue scale (VAS) (100 mm) and Borg scale obtained at baseline and 45 minutes after SC study dose and repeated until 240 minutes
• VAS for pain, somnolence, and anxiety
• Respiratory effort, including rate, cyanosis, and use of accessory muscles
• Pulse oximetry

• Mean change of VAS (–25, p < 0.01) and Borg scale (–1.20, p = 0.03) scores were significantly decreased with morphine compared to placebo.
• Respiratory effort (p = 0.05) and rate (p = 0.02) scores were significantly improved after morphine compared to placebo.
• No significant changes in pain, somnolence, anxiety, or oxygen percent saturation were found.

Intermittent injections of morphine at the doses used reduce cancer-related dyspnea. The changes in respiratory effort and rate but not anxiety support the theory that the benefit of morphine is unlikely related to somnolence or an effect on anxiety.

• This is a well-designed randomized, controlled study with the major limitation of sample size.
• The study points out the difficulty in conducting pharmacologic studies in patients with cancer and dyspnea.

To describe differences in bowel function with oral or IV opioids.

Patients who were admitted to a palliative inpatient unit for pain management had data retrospectively collected related to morphine-induced constipation. After IV morphine was administered and dose requirements were determined, patients were converted to oral morphine and then discharged.

• The study reported on a sample of 11 patients with cancer.
• Mean patient age was 43 years.
• The sample comprised eight men and three women.
• Patients were included in the study if they were admitted to a palliative care unit for IV morphine.
• Patients were excluded if they had gastrointestinal malignancy or disorders.

• Single site
• Inpatient
• India

The study has clinical applicability to end-of-life and palliative care.

This was a retrospective, descriptive study.

Visual analog scale

• Patients on IV morphine did not require laxatives for bowel movements to occur.
• Of patients switched to oral morphine, seven of 11 needed laxatives during their inpatient stay and were discharged with laxative prescriptions.

Patients on IV morphine were less likely to need laxative therapy to promote bowel function compared with patients on oral morphine. All patients on oral morphine needed laxative therapy.

• The sample size was extremely small.
• The design was retrospective and descriptive only.

Implications are limited because of the small sample size and other uncontrolled variables. More research is needed to determine whether IV morphine is less constipating than oral morphine and the applicability of this information in patient care.

To determine if massage therapy was effective relief for chemotherapy-induced nausea and vomiting (CINV) in children with cancer

Patients in the intervention group received a 20 minute massage 24 hours and 30 minutes before a chemotherapy infusion and 24 hours postinfusion. A trained massage therapist used a Swedish massage technique with effleurage, petrissage, friction, and tapping movements. Mild to moderate pressure was used. Subjects were randomized by a randomized number table. Patients could elect to use olive oil with the massage. No music was used during the therapy. The control group received normal care, but the therapist was present 24 hours and 30 minutes before an infusion as well as 24 hours postinfusion. Data were collected during chemotherapy and 48 hours postinfusion.

• N = 70  
• MEAN AGE = 8.6 years
• MALES: 52%, FEMALES: 48%
• KEY DISEASE CHARACTERISTICS: Majority of patients had acute lymphocytic leukemia 
• OTHER KEY SAMPLE CHARACTERISTICS: Pediatrics, ages 4–18 years

• SITE: Single-site  
• SETTING TYPE: Outpatient    
• LOCATION: Iran

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Pediatrics

Randomized, controlled trial

• Baxter Animated Retching Faces (BARF) scale (ages 4–9)
• Visual Analog Scale (VAS) (ages 9–18)

There were no significant differences between the intervention and the control group in terms of gender, type of cancer, or emetic potential of chemotherapy. There was no difference between groups in regard to nausea during chemotherapy. There was a significant difference in frequency (p = 0.001), duration (p = 0.002), and severity (p = 0.002) of nausea 48 hours after chemotherapy. There was no difference in vomiting at the time of chemotherapy, but there was a significant difference in the severity (p = 0.005) and frequency (p = 0.013) of vomiting 48 hours postinfusion.

Massage therapy may effectively decrease nausea and vomiting 48 hours after chemotherapy infusion in children.

• Small sample (< 100)
• Risk of bias (no blinding)
• Other limitations/explanation: Two different measurement instruments were used depending on the age of the child in the study.

Massage therapy, administered both before and after a chemotherapy infusion, may be effective in limiting CINV in the pediatric population. Massage was not effective at relieving anticipatory CINV that occurred at the time of infusion.

To assess the effectiveness of oxymorphone in the treatment of chronic pain

• Databases searched were MEDLINE, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials (CENTRAL).
• Search keywords were oxymorphone, oxymorphone ER, OPANA, oxycodone, randomized trial, randomized controlled study, pain, chronic pain, treatment, analgesia, human, cancer, back pain, and osteoarthritis. In addition, investigators performed manual searches based on reference lists.
• Studies were included in the review if they included level 1 evidence.
• The search did not involve exclusion criteria.

The search retrieved nine studies. Authors chose six studies for analysis. Five of the chosen studies were appropriate for meta-analysis. Only one study involved chronic pain resulting from a malignancy. Investigators, using guidelines published by the National Health Service Centre for Reviews and Dissemination, evaluated allocation procedures, concealment of allocation, blinding procedures,  distribution of known confounders between groups, whether study groups were treated the same except for the intervention, and whether intention-to-treat analysis was performed. Two reviewers independently reviewed and assessed all studies.

• The sample for analysis was composed of 1,426 patients. The sample range was 42–467 patients. Investigators analyzed data from 42 patients who experienced pain related to malignancies.
• The sample included adult patients with chronic low-back pain and pain related to osteoarthritis and cancer. The sample included opioid-naive patients and those who were taking opioids.
• Excluded from the study of cancer pain were patients who had undergone radiotherapy within the last two weeks.

In this study, oxymorphone 40–100 mg was associated with a significant reduction in the pain intensity experienced by patients with chronic pain unrelated to a malignancy. Total mean difference across studies was –12.88 (CI –17.08 through –8.68, p < 0.00001). Studies in which doses were titrated rather than fixed showed greater effect size. Adverse events were mild to moderate and similar to those associated with other opioids. The study of pain associated with malignancy, though small, demonstrated that oxymorphone was effective in the treatment of cancer pain and that switching between oxymorphone and oxycodone was feasible.

Findings suggest that oxymorphone is effective in chronic pain management. Note that the conversion ratio, oxymorphone to oxycodone, was 1:2.

Authors noted the high discontinuation rates in placebo groups; the high rates relate to the fact that some studies do not allow use of rescue medication. This fact has important implications regarding the design of studies in the field of pain management. Authors noted that regulators mandate placebo-controlled trials, and the authors highlighted the ethical concerns that such a requirement raises. In addition, authors noted the lack of placebo-controlled studies of patients with cancer pain.

To contribute preliminary evidence for the feasibility and potential effectiveness of a structured walking intervention on reducing cancer-related fatigue in order to plan for a full-scale study of effectiveness

The study consisted of an eight-week program with three intervention groups: one with the STEPS (a walking program using a pedometer) during rehabilitation, one with STEPS after rehabilitation, and one group with only the rehabilitation program for people with advanced cancer and a > 4 fatigue level on a Visual Analog Scale (VAS).

• SITE: Single-site    
• SETTING TYPE: Outpatient    
• LOCATION: McGill University Health Centre, Montreal, Canada

• PHASE OF CARE: Late effects and survivorship

A pilot randomized trial. The STEPS program was based on the participants’ current walking status and progressed according to fatigue level.

Instruments chosen to measure fatigue and symptoms of anxiety and depression included the following.

• Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System
• Fatigue Symptom Inventory (FSI)/Two-Minute Walk Test (2MWT)
• RAND-36 Survey
• Community Healthy Activities Model Program for Seniors (CHAMPS)
• EuroQol System
• Functional Assessment of Cancer Therapy (FACT-G)
• Hospital Anxiety and Depression Scale (HADS)
• Pittsburgh Sleep Quality Index (PSQI)
• Fatigue Visual Analogue Scale (VAS)

Results demonstrated that the pedometer-facilitated walking intervention adapted to fatigue levels (STEPS program) showed promise as an intervention to decrease cancer-related fatigue.

Compared to rehabilitation alone, the eight-week adaptive walking intervention reduced fatigue and improved physical function and well-being over a 16-week period and was sustained to six months.

• Small sample (< 30)
• Subject withdrawals ≥ 10%

Walking intervention is associated with a trend toward less fatigue; however, this study needs replication in the advanced cancer population. Effectiveness not established.

To compare efficacy and development of bacterial resistance with prophylactic antibiotic regimens of either COT/COL or CIP

Patients with acute myeloid leukemia (AML) were given antibiotic prophylaxis with either 960 mg cotrimoxazole twice daily and colistin 200 mg three times daily or 500 mg ciproloxacin twice daily. Those receiving CIP were also given cotrimoxazole twice daily two times per week for pneumocystis prophylaxis. All received antifungal prophylaxis. Colony-stimulating factors were given to some patients at the doctor's discretion. Patients receiving CIP did not receive antiviral prophylaxis. Infection-related outcomes were compared between these two cohorts. The study included patients over a four-year span of time. Environmental antimicrobial interventions were standard across both groups.

• N = 204  
• MEDIAN AGE = 62 years
• MALES: 59%, FEMALES: 41%
• KEY DISEASE CHARACTERISTICS: All had AML. The majority were receiving induction chemotherapy (61%), and 34% of chemotherapy courses were for consolidation.

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

• PHASE OF CARE: Active antitumor treatment

• Retrospective

• Fever defined at axillary temperature of at least 38º C
• Infections defined as occurrence of fever and detection of bacterial or fungal pathogens in at least one culture from sterile body sites
• Pneumonia defined as fever with infiltrates on radiological imaging
• Common Terminology Criteria for Adverse Events (CTCAE)

In both groups, the incidence of febrile neutropenia was about 80%. There were no differences between groups in infections. There were no differences between groups in detection or colonization of resistant organisms. There were no differences between groups in ICU useor differences in mortality related to underlying disease, infection, or septic shock. In both groups, infection was the major cause of death (70%). Overall, 8% of patients died. There were no differences between groups in treatment toxicity.

Both antibiotic prophylactic regimens resulted in similar patient outcomes, and both appeared to have similar efficacy.

• Risk of bias (no random assignment)

Although antibiotic prophylaxis with quinolones is generally preferred, antibiotic prophylaxis with COT/COL was essentially equally effective in this study, and might be considered an effective combination. Some studies have shown increase in quinolone-resistant organisms with standard quinolone prophylaxis. COT/COL prophylaxis may provide an alternative.

MEDLINE was searched for the 14 medical conditions for which the National Institutes of Health Acupuncture Consensus Development Panel (NIHCDP) concluded acupuncture was effective or could be useful. The two conditions in which acupuncture was found to be effective are the treatment of chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting. The remaining 12 conditions reviewed in the article were the effect of acupuncture on pain and the treatment of other conditions (e.g., addiction, stroke rehabilitation, and asthma).

Three of the studies reviewed examined the effect of P6 acupuncture on CINV. Although the chemotherapy agents were variable and various carcinomas were studied, strong evidence supported the use of acupuncture for greater antiemetic effect than antiemetics alone.

Evidence supports the use of acupuncture in the treatment of CINV and postoperative nausea and vomiting.

To compare the efficacy of two schedules of palonosetron versus ondansetron given by continuous IV infusion for treatment of chemotherapy-induced nausea and vomiting (CINV)

• Patients were randomly assigned to 1 of 3 intervention arms.
  • 8 mg of ondansetron IV bolus over 15 minutes followed by 24 mg of ondansetron given by continuous IV infusion starting 30 minutes before chemotherapy and lasting until 12 hours after chemotherapy infusion ended
  • 0.25 mg of palonosetron as IV bolus over 30 seconds, 30 minutes before start of chemotherapy daily during the chemotherapy cycle
  • 0.25 mg palonosetron as an IV bolus over 30 seconds, 30 minutes before the start of chemotherapy on days 1, 3, and 5 of treatment.
• All patients received 40 mg methylprednisolone as an IV bolus before each cytarabine infusion.
• Patient diaries were used to record episodes of vomiting, severity of nausea, use of rescue medication, and degree of impact on daily activities.
• Patients were followed for 7 days.

• The sample consisted of 143 patients.
• Median age was 53 years.
• The sample consisted of 47.6% female and 52.4% male patients.
• All subjects had acute myeloid leukemia, and all but five patients were undergoing induction therapy with idarubicin plus cytarabine or fludarabine plus cytarabine.

The study was conducted at an inpatient setting at the University of Texas M.D. Andersen Cancer Center.

All patients were in active treatment.

This was a randomized prospective study.

• Patients recorded nausea and vomiting severity in diaries.
• Nausea severity was measured on a Likert-type scale.
• Complete response (CR) was defined as no emesis and no use of rescue medications.
• Partial response (PR) was defined as one or fewer emesis episodes, no use of rescue medication during the study, and no more than grade 2 nausea.

• No significant difference was found in the proportion of patients who achieved a CR among groups.
• On day 1, more than 77% of patients in each group were free of nausea. The proportion of patients without nausea was similar across groups on days 2 through 5. On days 6 and 7, more patients receiving palonosetron than ondansetron were free of nausea (p < 0.03).
• No between-group differences in severity of nausea were recorded during days 1–5.
• Predictors of nausea in multivariate analysis were younger age, (p = 0.02), high-dose cytarabine plus idarubicin (p = 0.04), and prophylactic antibiotics (p = 0.009).
• The most commonly reported adverse events were headache and constipation.

Palonosetron was superior to ondansetron in reducing the prevalence of delayed nausea.

The study has potential bias because no control group or blinding was used.

Daily palonosetron appears to be more effective than the alternative used here for the prevention of delayed nausea. All the regimens here were similar in the early days of the therapy course, but palonosetron was significantly better in later days. Findings suggest that different drugs might be more helpful on different days throughout the course of chemotherapy, in concert with patterns seen in nausea.

To examine the effect of cognitive behavioral therapy (CBT) on sleep-wake outcomes in breast cancer survivors

Women who met criteria for chronic insomnia and had completed breast cancer treatment randomly were assigned to CBT intervention or a placebo behavioral intervention. Individual, weekly CBT sessions consisted of education, stimulus control, sleep hygiene education, and cognitive therapy provided by an advanced practice nurse with specialized training. The placebo intervention was based on desensitization therapy that had been used in previous insomnia trials as a placebo treatment. For both groups, sessions 1, 3, and 6 were provided in person, and sessions 4 and 5 were provided by telephone. Sessions were audiotaped and independently reviewed by a CBT therapist to ensure fidelity. Women were evaluated at three- and six-month follow-ups.

• N = 56
• MEAN AGE = 52 years
• FEMALES:100%
• KEY DISEASE CHARACTERISTICS: All had breast cancer and were 1–36 months post-initial treatment. Most had previous radiation and chemotherapy.
• OTHER KEY SAMPLE CHARACTERISTICS: The majority were Caucasian, well educated, and employed part- or full-time.

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

• PHASE OF CARE: Late effects and survivorship

• Randomized, single-blind RCT with attention control

• Sleep diary
• Piper Fatigue Scale
• Hospital Anxiety and Depression Scale
• Dysfunctional Beliefs and Attitudes About Sleep (DBAS-16)
• Patient knowledge test
• ISI measure of perceived insomnia
• Attentional function index
• EORTC-QLQ-C30

The CBT group did not show a significantly greater improvement in sleep outcomes immediately after the intervention, but scores were significantly better by the follow-up period (p = .003). Sleep efficiency increased by more than 11% in the CBT group, compared to an increase of 6.34% in the control group (d = 0.63). Sleep latency also improved more in the CBT group (d = 0.48, p = .007). No differences between groups were found for anxiety, depression, or fatigue.

Findings show that patients receiving CBT for sleep improved several sleep outcomes compared to individuals receiving a control intervention. The intervention did not demonstrate an effect on anxiety, depression, or fatigue.

• Small sample (less than 100)
• Findings not generalizable
• Other limitations/explanation: The sample had little diversity. The average baseline scores suggested that patients did not have clinically relevant levels of anxiety or depression.

Results of this study provide evidence of a moderate and significant effect of CBT on sleep outcomes among breast cancer survivors. This adds to the body of evidence that suggests effectiveness of this approach in managing sleep-wake disturbances.