To investigate whether melatonin could lower the risk of depressive symptoms in women with breast cancer in a three-month period after surgery with a secondary aim of assessing the effect of melatonin on anxiety, sleep, general well-being, fatigue, pain, and sleepiness in the immediate and long-term postoperative period

This study compared 6 mg oral melatonin versus a placebo daily one hour before bedtime for one week preoperatively and 12 weeks postoperatively (or a placebo administered on the same schedule).

• N = 54 intention to treat (28 intervention, 26 placebo); 43 analyzed per protocol (27 intervention, 16 placebo)
• MEAN AGE = 51 years (melatonin), 60 years (placebo) (SD = 46–68 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer; majority lumpectomy plus sentinel lymph node; majority received chemotherapy; majority did not receive antihormone therapy 

• SETTING TYPE: Outpatient    
• LOCATION: Denmark, Department of Breast Surgery

• PHASE OF CARE: Active antitumor treatment

Randomized, double-blinded, placebo-controlled trial

• Major Depression Inventory (MDI)
• Visual Analog Scale (VAS) and Karolinska Sleepiness Scale (KSS) for anxiety, sleep, general well-being, fatigue, and pain
• ActiGraph
• Sleep diary

The incidence of depressive symptoms (MDI = 21) at one point in the study period was significantly different between groups, as 45% (9/20) of patients had depressive symptoms in the placebo group versus 11% (3/27) in the melatonin group (p =  0.008); relative risk 0.25 (95%, CI: 0.076–0.80). The area under the curve for VAS data on anxiety, sleep, general well-being, fatigue, and pain and KSS for sleepiness in the short-term perioperative period showed no significant differences between the two groups.

This study demonstrated no effects of melatonin on fatigue; it may be useful for the prevention of depression in women with breast cancer.

• Small sample (< 100)
• Key sample group differences that could influence results
• Other limitations/explanation: A large number of patients assessed for eligibility did not meet criteria; depression, not fatigue, was the primary endpoint; and there were more participants in the placebo group ineligible for analysis than the experimental group.

Melatonin is not effective in treating cancer-related fatigue; it may be useful in preventing depression.

To determine the effectiveness of melatonin on postoperative cognitive function and sleep quality in women who underwent breast cancer surgery

The intervention group received 6 mg of melatonin orally one hour before bedtime one week prior to surgery through 12 weeks postoperatively. The control group received a placebo medication packaged by the hospital pharmacy with the same instructions. Both the placebo and melatonin were labeled and administered identically. Neuropsychological testing was conducted within one week preoperatively and after two and 12 weeks postoperatively. Sleep assessments were collected three days preoperatively to eight days postoperatively (short-term) and 2–12 weeks postoperatively (long-term).

• N = 54 (intervention 28, placebo 26)  
• MEAN AGE = 51 years (intervention), 60 years (placebo)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Women who were 30–75 years old undergoing a lumpectomy or mastectomy and were American Society of Anesthesiologists classes I–III
• OTHER KEY SAMPLE CHARACTERISTICS: Exclusions included patients who were pregnant; depression as indicated by the Major Depression Inventory; current chemotherapy; patients taking SSRIs, antithrombotic agents, MAO inhibitors, calcium channel blockers, or insulin; patients with pre-existing neurologic diseases, sleep apnea, another sleep disorder, kidney disease, autoimmune disorders, or an allergy to melatonin

• SITE: Single-site    
• SETTING TYPE: Multiple settings    
• LOCATION: Herlev Hospital Department of Breast Surgery, Copenhagen, Denmark

• PHASE OF CARE: Active antitumor treatment

Double-blinded, randomized, controlled study

• Mini-Mental State Examination (MMSE)
• International Studies of Postoperative Cognitive Dysfunction (ISPOCD) Test Battery
  • Visual verbal learning test 
  • Concept shifting task
  • Letter-digit coding test 
  • Stroop color-word test
• Sleep diary (sleep latency, number of awakenings, total sleep, sleep efficiency) 
• Sleep Visual Analog Scale (VAS)
• Major Depression Scale (MDS)

There were no statistically significant differences between group characteristics. There was no evidence of cognitive impairment two weeks postoperatively in either group; however, there was a decline in cognitive performance (as a composite z-score) in the placebo group, 6.3%, compared to no decline in the intervention group (p = .38). Perioperative sleep efficiency was significantly greater for the intervention group (p = .02). Postoperative total sleep time was greater in the intervention group (p = .03). Side-effect frequency was similar for both groups; however, there was a difference in types of effects reported. Intervention side effects included dizziness (14%), headache (10%), and paresthesias (10%), and the placebo group experienced headache (27%), difficulty falling asleep (13%), and nausea (13%).

Although cognitive impairment was not found to be a significant problem in this sample, subjects who received melatonin had greater sleep efficiency and total sleep time postoperatively than those in the placebo group. In addition, subjects who received melatonin tended to have less cognitive decline although it was not statistically significant.

• Small sample (< 100)
• Subject withdrawals ≥ 10%
• Other limitations/explanation: More subjects in the placebo group withdrew (n = 10) than in the intervention group (n = 1).

Melatonin may be useful as an intervention to reduce cognitive difficulties and improve sleep, but further study is warranted.

To evaluate the effectiveness of a comprehensive exercise program consisting of low-to-moderate intensity aerobic and resistance exercise twice a week for 16 sessions to assess improvements in physical function, fatigue, and mood.

Patients received low-to-moderate aerobic and resistance exercise, education, and support twice weekly. At the start of each session, a specialist obtained blood pressure, oxygen saturation, and heart rate for each patient. Patients performed aerobic exercise on a seated machine or treadmill. Progression was obtained through increased exercise duration by adding small increments of three to five minutes per session as tolerated. All patients were able to progress to 40 minutes of aerobic exercise before the end of 16 sessions. Education included various topics focused on symptom management, coping, and wellness, including support groups, survivorship, resources, spirituality, stress management, chemotherapy, radiation, nutrition, energy conservation, relaxation and imagery, drugs and herbs, fatigue and pain, humor therapy, exercise safety and benefits, diagnostic testing, communication issues, financial issues, complementary therapy, and infection control. Average attendance per month was 12 sessions. Support included peer support, exercise environment conducive to discussion within the group, and facilitation of relationships of sharing and encouragement. The specialist inquired about how patients were coping with their disease, side effects, and treatments.

• The sample was comprised of 39 patients (77% female) in active treatment and cancer survivors beyond treatment.
• Patients were older than 18 years. Mean age was 63 years (range 42–87 years; standard deviation = 10.61 years).
• Patients had 13 different cancer types, with the majority being breast cancer (39%). The most common diagnosed stage was stage III (26%); patients also had stage I (23%), stage II (21%), and stage IV (14%) cancer. One patient had ductal carcinoma in situ (DCIS) of the breast. 
• Of the patients, 24% stated that exercise was new to them and 30% indicated that exercise was not at all new to them.

• Single site
• Cancer Center in a 350-bed teaching hospital in east central Indiana

The study was a retrospective analysis of archived data. Patients were eligible if they had a diagnosis of cancer; type and age of diagnosis were not factors.

• Six-minute walk test
• Profile of Mood States (POMS) Questionnaire to evaluate personal and social integrity
• Piper Fatigue Scale (PFS) Questionnaire to measure conservation of energy pre- and postprogram
• The main variables were physical function, fatigue, and mood.

• Pre- and postprogram outcome measures had significant differences (p < 0.05). Patients had significant improvements in physical function, fatigue, and mood.
• Change in fatigue:  On average, patients reported less fatigue on the PFS compared to before the program. Of the sample, 75% improved and 25% stayed the same.
• The study had a small sample size.
• No control comparison was used.

A comprehensive exercise program consisting of low-to-moderate intensity aerobic and resistance exercise, education, and support twice a week for eight weeks resulted in significant improvements in physical function, fatigue, and mood in patients in active treatment and in cancer survivors beyond treatment.

• The study lacked a control group and uniformity. However, the heterogenicity of the group demonstrated that, regardless of diagnosis and stage, improvements can be achieved.
• Of the patients, 69% had a break in exercise consistency.
• Educational sessions were optional, and not all patients attended educational sessions regularly; therefore, the direct role of education on outcome is unknown.

Further studies may need to be conducted comparing the degree of benefit achieved by patients in a comprehensive program versus a single-component exercise or support group program. The study encouraged the use of low-to-moderate intensity exercise to benefit people with all types of cancer. Further studies need to be completed to determine the best mode, duration, and intensity of exercise for survivors. The authors can say with some certainty that low-to moderate intensity exercise produces significant benefits for people with cancer without causing participant overload or drop-out.

The Cancer Exercise Program (CEP) is based on exercise, education, and support. Patients attended CEP sessions twice a week as able until they completed 16 sessions. Exercise mode was based on patients’ fitness level; individualized heart rate target ranges were supplied. The education component focused on symptom management, coping, survivorship, resources, spirituality, stress management, treatment, and other topics. Education was an optional but encouraged component of the CEP. Peer support was encouraged. The exercise specialist also provided support.

• The sample was composed of 39 participants.
• The sample included 13 cancers.
• Most patients had finished cancer treatment within six months of beginning the program.

• Single site
• 350-bed teaching hospital
• Midwestern city, United States

Nonrandomized retrospective analysis of archived data

• The Revised Piper Fatigue Scale measured fatigue.
• Profile of Mood States questionnaire measured mood.
• Investigators measured fatigue and mood before the first exercise session and after all the sessions. Investigators also measured physical function.

• Patients reported a significant decrease in total mood disturbance after CEP participation, compared to before CEP.
• Of all participants, 80% improved; the total mood disturbance of 20% of patients stayed the same or worsened.
• Fatigue and physical function improved.

• The fact that this study was a retrospective analysis was a limitation.
• The study had a very small sample size, and it lacked a control group. Patients were compared to themselves only.
• The study included patients with various types of cancer.
• Educational sessions were optional.
• The number of sessions attended or the topics covered during sessions attended may have affected outcome.

Desmopressin (DDAVP) was administered 0.3 mcg/kg IV over 30 minutes. Blood levels of coagulation factor FVIII activity, von Willebrand Factor Antigen, collagen-binding activity, and PFA-100^® closure times were measured before and at 60, 120, and 240 minutes after DDAVP administration.

• N = 51  
• AGE = Older than 2 years
• KEY DISEASE CHARACTERISTICS: 26 patients with von Willebrand disease, 15 patients with platelet function defects (PFDs)
• OTHER KEY SAMPLE CHARACTERISTICS: Inclusion baseline platelet count was higher than 50.

• LOCATION: Germany, January 2000–March 2007

• Retrospective study

• Evaluated the results of DDAVP testing in patients with congenital bleeding disorders

Twenty-four of 26 patients in the von Willebrand group (92%) had an overall positive response rate. Fourteen of 15 patients in the PFD group (93%) had a positive response. One patient in the von Willebrand group and two patients in the PFD group were nonresponders. Mild side effects of flushing or headache occurred in some patients. Side effects were not recorded exactly in the chart. Hemostatic effects differed between individuals and were dependent on coagulation disorder.

DDAVP “challenge” testing is recommended before its first therapeutic use in bleeding episodes or surgical procedures.

• No current standardization of DDAVP testing
• Small group number
• Seven-year study
• Specific pediatric subset

To determine if a taurolidine catheter lock can reduce catheter-related bloodstream infection (CRBSI) in children with tunneled central venous catheters (CVCs)

Patients were randomized to receive either locks with 250 IE heparin in 2.5 ml normal saline or with 2.5 ml taurolidine 1.35%/sodium citrate 4%/heparin 100 IE/ml. Catheters were flushed once weekly. Catheter insertion was done according to standards in all patients, and bio-occlusive dressings were changed weekly after the skin was cleansed with chlorhexidine every three days. Tunneled lines and total implantable devices were included.

• N = 112 patients, 129 catheters  
• MEDIAN AGE = 6 years
• AGE RANGE = 0–19 years
• MALES: 61%, FEMALES: 39%
• KEY DISEASE CHARACTERISTICS: Multiple tumor types; the most common was leukemia or lymphoma.
• OTHER KEY SAMPLE CHARACTERISTICS: 113 of the 129 catheters were totally implantable devices.

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

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

• Randomized, two-group, open-label design

• Tunnel infection was defined as inflammation extending more than 2 cm along the tract of the CVC.
• CRBSI was defined as growth of microbes from a sample drawn from the CVC at least two hours before microbial growth was detected in a peripheral blood sample, or cultures in which a pathogen was found in the central sample but not in the peripheral sample.
• Probable CRBSI was determined if a recognized pathogen was cultured from at least one blood sample, or a common skin contaminant was cultured from two or more samples obtained at separate occasions.

There were 33 episodes of CRBSI. The rate of total bloodstream infections per CVC days was seen in those with taurolidine locks (1.2 per 1,000 CVC days) compared to those with heparin locks (2.5 per 1,000 CVC days) (IRR = 0.49. p =.004). The rate of CRBSI in the experimental group was 0.4/1,000 CVC days compared to 1.4/1,000 CVC days (IRR = 0.26, p = .001). CVC survival was similar in both groups, with a median of 256 days in the heparin group and 300 days in the taurolidine group. Power analysis showed that the sample size was sufficient to detect a relative risk of 0.25 with the intervention.

Use of taurolidine citrate catheter locks was effective in preventing CRBSI in pediatric patients with long-term CVCs. The majority of these were totally implantable devices.

• Risk of bias (no blinding)
• Risk of bias(sample characteristics)
• Other limitations/explanation: Open-label design; the majority of patients had totally implantable devices, so it is not clear if findings would apply similarly to only tunneled catheters.

CRBSI is a major concern for patients with cancer who are immunocompromised. Results of this study provide an intervention that appears to prevent CVC-related infections with long term CVCs. Because the majority of catheters in this study were totally implantable devices, it is not clear if this will apply to other long- or short-term CVCs, but further study in these areas is warranted.

The purpose of the study was to compare the effect of catheter locking with taurolidine versus heparin in biofilm formation in central venous catheters.

In the standard arm, catheters were locked with 250 IU heparin in 2.5 ml normal saline while in the experimental arm they were locked with taurolidine 2.5 ml in a sodium citrate and heparin solution. All catheters were either tunneled or totally implanted devices and chosen at the physician’s discretion. Biocclusive dressings were changed every three days and the skin was cleansed with chlorhexidine with dressing changes.

• The sample contained 48 participants, aged 0–19 years.
• All participants were males
• Patients had any oncological disease requiring a tunneled CVC

A single-site inpatient setting in Denmark

• The phase of care was active antitumor treatment
• Application was for pediatrics

Prospective, randomized, controlled, open-labeled study

• After removal, catheters were examined by standardized scanning electron microscopy to assess quantitative biofilm formation. Quantitative and semi-quantitative cultures were also performed using scanning electron microscopy (SEM).
• Catheter-related bloodstream infection (CLABSI) was defined as microbe growth from a blood sample drawn for the CVC at least two hours before microbial growth was detected in a peripheral vein blood sample.

There was no significant difference in the formation of biofilm between the two groups (p = 0.13). A reduction in catheter-related blood stream infections (CRBSIs) was demonstrated in the taurolidine arm (p = 0.03). CVCs locked with heparin were removed after a median of 246 days (range = 40–1,081) and after a median of 301 days (range = 51–590) in those with the experimental lock solution.

The trial confirmed that use of taurolidine as catheter-lock compared with heparin reduced the rate of CRBSIs. This reduction was not related to a reduction in the biofilm formation.

• Small sample size (less than 100)
• Risk of bias (no blinding)
• Risk of bias(sample characteristics)
• Measurement validity/reliability questionable
• All participants in this study were male.
• Also, the number of hematological malignancy were unevenly distributed with a large portion of these patients in the experimental arm. This may have contributed to a higher risk of infection.
• Dehydration of specimens for SEM caused the specimens to become fragile, potentially affecting the accuracy of the study.

No difference in CVC survival was noted, requiring that they will be changed at the same rate as before. Findings suggest that taurolidine used as a catheter lock was associated with lower incidence of CRBSI.

To investigate the effects of calcium and magnesium infusions on oxaliplatin pharmacokinetics and neurotoxicity

Patients were randomized to receive either 1 g calcium and 1 g magnesium IV or placebo 15 minutes before and after a two-hour oxaliplatin infusion on cycle 1, then crossed over to the other intervention on cycle 2. Blood samples were obtained at multiple time points during and after the oxaliplatin infusion for pharmacokinetic analysis. Other study measures were obtained on day 2 and at the end of treatment cycles 1 and 2.

• N = 19
• MEDIAN AGE = 62 years
• AGE RANGE = 31–77 years
• MALES: 60%, FEMALES: 40%
• KEY DISEASE CHARACTERISTICS: Colorectal adenocarcinoma—95% had stage 3 or 4 disease; patients were receiving either a XELOX or modified FOLFOX6—all received the same dosage level of oxaliplatin
• OTHER KEY SAMPLE CHARACTERISTICS: Two patients had diabetes mellitus.

• SITE: Single site 
• SETTING TYPE: Outpatient 
• LOCATION: New Zealand

• PHASE OF CARE: Active antitumor treatment

• Double-blind, placebo-controlled, crossover trial

• EMG with severity score calculation from severity of hyperexcitability and number of muscles affected—four-point severity score
• Patient questionnaire of presence or absence of acute neurotoxicity symptoms

No evidence existed of a pharmacokinetic interaction between calcium and magnesium infusions and oxaliplatin. Most patients demonstrated EMG changes about 24 hours after oxaliplatin. No differences were seen between the experimental and control conditions.

Findings did not show a benefit of calcium and magnesium infusions for prevention of neurotoxicity symptoms from oxaliplatin.

• Small sample (less than 100)

Findings demonstrate that calcium and magnesium infusions did not have a preventive effect on the development of neuropathy symptoms in patients receiving oxaliplatin. Findings also showed that EMG changes happened within 24 hours of treatment. Nurses need to be aware that neuropathic symptoms can develop very quickly and need to assess for such changes early and on a routine basis to identify patients who may need dose reduction or other interventions.

To assess the effect of thalidomide on delayed chemotherapy-induced vomiting

Patients were randomly allocated to treatment with thalidomide 25 mg four times per day and 50 mg at night beginning the day before chemotherapy. Both the intervention and treatment groups were given azasetron 10 mg IV 30 minutes before chemotherapy administration. Patients had received at least one cycle of chemotherapy prior to study inclusion.

• N = 78   
• MEAN AGE = 50.3 years
• AGE RANGE = 26–75
• MALES: 57.69%, FEMALES: 42.31%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Patients were receiving platinum-based chemotherapy. Lung, gastric, and ovarian cancers
• OTHER KEY SAMPLE CHARACTERISTICS: Excluded patients with vomiting related to a brain tumor, gastrointestinal obstruction, etc.

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

PHASE OF CARE: Active antitumor treatment

Randomized, controlled trial

• Common Terminology Criteria for Adverse Events (CTCAE), version 4 (grade 1 considered completely controlled)
• World Health Organization (WHO) adverse reaction grading of chemotherapy side effects

Delayed vomiting was fully or partly controlled in 88% of the treatment group and in 66% of the control group (p = 0.023).

Thalidomide might be helpful to control chemotherapy-induced nausea and vomiting.

• Small sample (< 100)
• Risk of bias (no blinding)
• Measurement/methods not well described
• Timing of data collection not described
• Patients did not receive antiemetics according to established guidelines, and control rates were below those reported with the use of full antiemetic prophylaxis as described in guidelines.

Thalidomide might be useful for the control of chemotherapy-induced nausea and vomiting; however, additional well designed research is needed to determine the role of thalidomide as an option or adjunct to reduce nausea and vomiting.

The data analysis included medical records of 119 patients with lymphedema secondary to breast cancer who were receiving a protocol of complete decongestive therapy (CDT), including manual lymph drainage (MLD), compression bandages, skin care, and exercise. MLD was performed twice weekly by a physical or occupational therapist trained in the Foldi method of lymphatic decongestion. Between sessions, patients wore elastic compression bandages, changed twice daily. Patients were instructed in skin and nail care. Therapy was divided into two phases: induction and maintenance. During the eight-week induction phase, the intervention was performed twice weekly. The maintenance phase was individualized to patient needs. Absolute volume and percentage of volume of lymphedema were compared before and after treatment. The degree of chronic pain and the need for pain medication also were assessed. Using medical records, data were collected for all patients receiving CDT for lymphedema.

Only those with unilateral lymphedema of the upper extremity that resulted from the treatment of breast cancer were included.

The study used a retrospective design.

• Pain was measured on a 1–10 scale.
• Water displacement was used to measure volume.

• Mean initial arm volume was 709 ml, and the percentage of lymph was 31%; the induction phase reduced initial arm volume to 473 ml and 18%.  
• Before therapy, 76 patients had chronic pain, and 41 required oral pain medications, which CDT reduced to 20 and 11, respectively.
• Pain was reduced from 6.9 to 1.1

• Exclusion criteria were not defined.
• The results cannot clearly be attributed to MLD versus physical therapy.
• The study was not randomized.