To determine the effectiveness of laxative administration for constipation in patients receiving palliative care; to differentiate among laxatives being used regarding efficacy for constipation management.

Databases searched were Medline, Embase, CANCERLIT, PubMed, CINAHL, System for Information on Grey Literature in Europe (SIGLE), National Technical Information Service (NTIS), Department of Health and Social Security (DHSS-DATA), Science Citation Index, Cochrane Central Register of Controlled Trials (CENTRAL), Dissertation Abstracts, and the Index to Scientific and Technical Proceedings. Conference proceedings and references of articles reviewed were also hand searched.

Search keywords were palliative care, cathartics (adverse effects; therapeutic use), constipation (drug therapy), and randomized controlled trial as topic. 

Studies were included in the review if they

• Were a randomized controlled trial (RCT) of the efficacy of laxatives in palliative care patients
• Reported on a sample of adult patients receiving palliative care interventions who reported constipation
• Involved the use of any oral or rectal laxatives
• Included the outcome measures patient-reported relief of constipation in terms of frequency and ease of defecation, relief of related symptoms such as distension, appetite improvement, and improvement of quality of life.

Studies were excluded if they included healthy volunteers, patients with constipation as a result of drug misuse, patients with bowel obstruction, or other interventions such as opioid antagonists.

Two hundred twelve studies were initially retrieved. After removal of duplicates and studies that did not meet inclusion criteria, three studies were finally included. Study quality was assessed using the Jadad scale and additional criteria identified including issues of accrual, homogeneity, attrition, interventions, quality of outcome measurement, and clarity of results presentation. The review provided extensive detail on quality assessment findings and rationale for study exclusion. Included studies used senna, lactulose, danthron combined with poloxamer, misrakasneham, and magnesium hydroxide combined with liquid paraffin.

The final sample of three studies involved a total of 162 patients, with study samples ranging from 36 to 75.

• One study found no differences between groups taking senna and lactulose.
• One study found no difference between patients with advanced cancer taking misrakasneham and senna.
• One study of hospice patients with cancer found that those taking lactulose plus senna had significantly higher stool frequency than those using danthron and poloxamer. This pattern was true in patients at varied levels of opioid use. This study used a crossover design and showed that significantly fewer patients reported constipation when taking lactulose plus senna.
• One study in hospice patients with cancer found no difference between patients taking lactulose plus senna versus those taking magnesium hydroxide and liquid paraffin. In patients taking different levels of opioids, a trend to less constipation existed in the lactulose plus senna group, but the trend was not statistically significant.
• No significant differences were found between opioid-level groups in terms of laxative results.
• Diarrhea was reported as an adverse effect in studies for both senna and lactulose.
• Where patient preference was reported, no differences were found between most combinations. Patients preferred lactulose plus senna over magnesium hydroxide and liquid paraffin. The basis of preference was usually taste.
• The authors included a general literature review of constipation treatments.

The treatment of constipation in palliative care patients is not based on sufficient data from RCTs. Recommendations for laxatives may be based as much on cost as on efficacy. Polyethylene glycols are widely used in palliative care despite lack of evidence. The authors did not note evidence in this area in other patient populations that may be applicable.

This review and included studies did not provide sufficient information to draw conclusions about the laxatives in terms of weighing effectiveness versus adverse side effects.

• Little research exists in this area, and very few direct comparisons have been done between laxative classes and combinations to compare efficacy.
• Because of the lack of evidence in this area, determining most effective treatments is difficult.

This area could benefit from research to compare effects and cost effectiveness. Some findings suggested effect and preference for lactulose combinations, whereas lactulose tends to be much more expensive than alternatives.

Test the effect of Tibetan sound meditation on cognitive function

Patients randomly were assigned to the treatment group or a wait list control group. The intervention consisted of 12 meditation sessions that were 60 minutes long and incorporated instructions on developing breathing, awareness, and concentration skills, as well as visualization maneuvers. The intervention was offered twice a week over six weeks. A CD recording and printed materials were provided to the participants with the expectation that they practice the intervention independently at home. Objective and subjective outcome measures were evaluated at baseline and one month after completion of the intervention. Subjective measures also were completed during the last week of the intervention. Class attendance and participant satisfaction were tracked to measure the feasibility of the intervention program.

• N = 42 (18/24)  
• MEAN AGE = 53.6 years
• MALES: 0%, FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All subjects had breast cancer, had received chemotherapy 6–60 months prior to study participation, and were on hormonal therapy at the time of enrollment.
• EDUCATION: Some college or higher: 95.6%, TSM: 74.9%

• SITE: Single-site  
• SETTING TYPE: Outpatient  
• LOCATION: MD Anderson Cancer Center

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

Randomized clinical trial

• Digit span test
• Digit symbol test
• Controlled Oral Word Association Test
• Rey Auditory Verbal Learning Test
• Functional Assessment of Cancer Therapy (FACT)-Cog
• Center for Epidemiologic Studies Depression Scale (CES-D)
• Pittsburgh Sleep Quality Index (PSQI)
• Brief Fatigue Inventory (BFI)
• Medical Outcomes Study 36-item (SF-36)
• Functional Assessment of Chronic Illness Therapy—Spiritual Well-being Scale (FACIT-Sp)

No significant differences were seen between the intervention or control groups in either objective or subjective measures of cognitive function over time. Although significantly less depressive symptoms were found in the treatment group (p = 0.05) during the last week of the intervention, this effect was no longer significant one month later, indicating that the result was not sustainable. No significant differences between groups over time were found for fatigue or sleep-wake disturbances. Although all treatment group participants attended at least 50% of the class sessions, compliance was a variable for both class and individual participation.

Findings from this study do not provide clear support for a significant effect of Tibetan sound meditation on cognitive function, fatigue, or sleep-wake disturbances. However, this intervention may have a limited, short-term effect on decreasing depression.

• Small sample (< 100)
• Risk of bias (no appropriate attentional control condition)
• Unintended interventions or applicable interventions not described that would influence results
• Findings not generalizable
• Subject withdrawals ≥ 10%
• Feasibility may be an issue, as evidenced by subject withdrawal prior to the initiation of the intervention (may indicate that the “treatment” is too burdensome) and the variability in overall treatment participation. Generalization of the result to all patients with cancer is not possible due to the population used for the study.

Although this treatment was not associated with improvements in objective or subjective measures of cognitive function, it was underpowered and lacking consistent patient compliance with the intervention. Further research with larger sample sizes may be warranted to determine effectiveness.

To examine the feasibility and preliminary efficacy of Tibetan yoga practice as a supportive approach for patients and caregiver dyads during radiation therapy for lung cancer

Participants had two to three weekly sessions of yoga for 45–60 minutes over five to six weeks. The program included deep breathing awareness and visualization, guided meditation, compassion-based meditation, and gentle movements coordinated with specific breathing patterns. Patients and caregivers completed study measures at baseline and at the end of the program.

• N = 10 dyads  
• MEAN AGE = 71.22 years (patients, range = 61–82 years); 68.77 years (caregivers, range = 61–78 years)
• MALES: Patients 50%; caregivers 10%, FEMALES: Patients 50%; caregivers 90%
• KEY DISEASE CHARACTERISTICS: All patients had lung cancer and were receiving radiation therapy. 50% had stage IIIb disease. Average time since diagnosis was 2.88 months, range 1.13–5.97 months.
• OTHER KEY SAMPLE CHARACTERISTICS: Slightly greater than 50% of participants had some college level or higher education, 80% were white, and 75% had incomes greater than $50,000 per year.

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

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care  

Single-group, prospective pilot study

• Center for Epidemiologic Studies Depression Scale (CES-D)
• Anxiety dimension of the Brief Symptom Inventory (BSI)
• Pittsburgh Sleep Quality Index (PSQI)
• Brief Fatigue Inventory (BFI)
• Medical Outcomes Study Short-Form Health Survey (SF 36)
• Functional Assessment of Cancer Therapy Spiritual Well Being Scale (FACT-Sp)
• Finding meaning in cancer scale

Ten of 19 consenting dyads completed the study and attended a mean of 12 sessions (range = 6–15). For patients, there was a significant increase in spiritual well-being (d = 1.12, p = .03), improvement in sleep (d = .60), and depressive symptoms (d = .52). There were small effects for anxiety. For caregivers, there were significant decreases in fatigue (d = .89, p = .03) and anxiety (d = .81, p =.04) and some reduction in sleep disturbance (d = .71, p =.08). Class attendance and home practice frequency was not associated with differences seen in symptoms for either patients or caregivers.

A couple-based yoga program was seen as feasible for patients, including those with advanced disease. Medium effect sizes were seen for depressive symptoms and sleep disturbance.

• Small sample (< 30)
• Risk of bias (no control group)
• Subject withdrawals ≥ 10%

Couple-based yoga sessions were shown to be feasible, and findings suggest that this type of supportive care during radiation therapy may be beneficial in some patients and caregivers for symptoms of fatigue, anxiety, depression, and sleep disturbances. The high drop-out rate suggests that many patients may not be interested or able to participate in such a program, but for those who are interested, it may be helpful. The fact, however, that the number of sessions attended and frequency of home practice were not related to the magnitude of results seen causes one to question whether it was the yoga practice or general support and attention provided that caused effects.

The purpose of the study was to compare efficacy of pegfilgrastim and filgrastim administered after chemotherapy in children with Ewing sarcoma. 

All patients received both types of G-CSF in different treatment courses of chemotherapy, which consisted of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE); vincristine, atinomycin D, and ifosfamide (VAI); or vincristine, atcinomycin D, and cyclophosphade (VAC). A single injection of pegfilgrastim 100 mcg/kg subcutaneously or a daily injection of filgrastim 5–10 mcg/kg subcutaneously was administered 48–72 hours after the completion of chemotherapy. Twenty children were included. A total of 178 chemotherapy courses were administered and evaluated, including 134 courses with pegfilgrastim and 44 courses with filgrastim.

• 20 participants
• Median age was 12.8 years, with a range of 9–17 years.
• Females made up 65% of the sample; males made up 35%.
• Participants had  Ewings sarcoma
• Participants' weight range was 28–90 kg  with median weight of 45.2 kg.
   

Single-site location in Marseille, France
 

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

Retrospective chart review

• Proportion of chemotherapy courses with grade 4 neutropenia    
• Duration of grade 4 neutropenia
• Proportion with severe neutropenia
• Proportion with febrile neutropenia
• Duration of antibiotic treatment
• Duration of hospitalization
• Percentage of patients receiving transfusion
   

Considering all types of chemotherapy combined, those courses in which pegfilgrastim was used were associated with a significantly lower incidence versus severe neutropenia (0.21 versus 0.85; p = 0.034), a shorter duration of severe neutropenia (0.49 versus 2.36 days; p = 0.01), and a shorter duration of antibiotic treatment (1.07 versus 4.22 days; p = 0.03) compared with courses with filgrastim. No statistically significant differences were observed for the proportion of febrile neutropenia, duration of hospitalization, or transfusions.

Using pegfilgrastim after chemotherapy courses was associated with significantly reduced frequency and shorter duration of severe neutropenia compared with those courses followed by filgrastim.

•  Small sample (less than 30 participants)
•  Administration of G-CSF was not randomized.

Randomized, controlled trials are needed to confirm the results.

To examine the effects of slow-stroke back massage on the symptom cluster of fatigue, pain, and sleep disturbance

Patients were assigned to massage or usual care control groups according to a fixed approach such that the first three patients entered into the study were assigned to the intervention, the next three to control, and so on. Massage was provided by two oncology nurses who had four months of professional training. The intervention group received 10-minute massage sessions every other day for four weeks in a special room in an outpatient setting. Control patients were given social attention. Data collectors were blinded to the study assignment. Soothing music was provided during the massages.

• N = 60   
• MEAN AGE = 34.5 years
• MALES: 51.7%, FEMALES: 48.3%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: All had acute leukemia and were between the first and third chemotherapy cycles
• OTHER KEY SAMPLE CHARACTERISTICS: Intensity of at least 3 on numeric scales for pain, fatigue, and sleep disorders; and a score of at least 5 on the Pittsburgh Sleep Quality Index (PSQI)

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

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Palliative care 

• Single-blind, randomized, controlled trial

• Numeric rating scales for pain, fatigue, and sleep quality
• Pittsburgh Sleep Quality Index (PSQI)

Repeated measures ANOVA showed a significant difference in pain, fatigue (p = 0.001), and sleep disorder intensity (p = 0.015) from baseline to the end of week 5. By the end of week 4, PSQI scores showed improvement in the intervention group compared to controls (p = 0.003). Trends showed a consistent decline in pain, fatigue, and sleep disturbance intensity during the four weeks in which massage was done in the intervention group, while in the control group, intensity of these symptoms increased.

Sessions of slow-stroke back massage were shown to reduce intensity of pain, fatigue, and sleep disturbance.

• Small sample (< 100)
• Risk of bias (no appropriate attentional control condition)
• Unintended interventions or applicable interventions not described that would influence results
• The effect of the music component cannot be determined.
• It is unclear if the attempted attention control provided was similar in amount of time to time spent with intervention patients.
• Lack of any sample contamination could not be assured. 
• At the end of the four weeks, increasing symptom intensity was shown in the massage group

Massage was shown to be of benefit in dealing with the symptoms of pain, fatigue, and sleep disturbance during the treatment phase for patients with leukemia. Nurses can apply massage as a low-risk intervention. Trend results in this study suggest that massage likely has only short-term effects as symptom intensity levels began to rise after the four-week intervention. Ongoing research is needed to evaluate the optimum frequency and timing  of massage and duration of effects.

To determine the feasibility and effectiveness of speed-feedback therapy on improving cognitive function in elderly patients with cancer

The intervention consisted of subjects pedaling for five minutes on a bicycle ergometer once per week for four weeks compared to usual daily life activities. The bicycle ergometer was linked to a computer with the screen displaying the target speed, revolutions per minute, and a changing path for the subjects to follow. Subject’s actual speed and revolutions were displayed as the subject tried to match the target speed and revolutions on the path on the screen. The exercise load was set at 20 W, and the maximum number of rotations was set at 80 revolutions per minute. Demographic data were collected at baseline. Cognitive function and other assessments were obtained at baseline and at week 4.

• N = 78 (38 intervention, 40 control)
• MEAN AGE = 74.24 years
• MALES: 45%, FEMALES: 55% 
• KEY DISEASE CHARACTERISTICS: All participants were diagnosed with either breast or prostate cancer irrespective of stage or treatment modalities. Most subjects were undergoing treatment (53% intervention, 70% control).
• OTHER KEY SAMPLE CHARACTERISTICS: Average education = 12.11 years

• SITE: Single-site    
• SETTING TYPE: Outpatient    
• LOCATION: Hiroshima University Hospital rehabilitation center, Japan

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

Randomized, controlled trial design; outcomes evaluator blinded to group assignment

• Frontal Assessment Battery (FAB)
• Barthel Index (BI)
• Lawton and Brody Instrumental Activities of Daily Living (IADL)
• Functional Assessment of Cancer Therapy-General (FACT-G) version 4

There were more subjects who underwent radiation therapy in the intervention than the control group (p = .01). There were significant differences between groups in the FAB change score for time effect (F = 24.39, p < .001, partial ɳ² = .247), group effect (F = 9.26, p = .003, partial ɳ² = .109), and interaction (F = 7.88, p = .006, partial ɳ² = .094). Younger age was an independent factor associated with greater improvement in FAB scores (p = .018, β = -.264). There were no differences between groups for BI, IADL, or FACT-G scores at baseline or over time.

Findings from this study suggest that speed-feedback therapy may improve cognitive function. However, this intervention required a bicycle ergometer associated with a computer and training by professionals in a hospital setting, which may impact accessibility and costs. Additional studies in other cancer diagnoses with longitudinal follow-ups to demonstrate sustained cognitive improvements is warranted.

• Small sample (< 100)
• Intervention expensive, impractical, or training needs

Speed-feedback therapy with a bicycle ergometer may be a potential intervention to improve cognitive function, particularly sustained attention. Additional research with larger sample sizes and a longer follow-up period is needed to determine the effectiveness and the sustainability of any improvements in cognitive function.

To review available literature to develop guidelines for the use of laser and other light therapies in patients with cancer

• This review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO).
• Database searched was MEDLINE.
• Search keywords were oral mucositis OR stomatitis AND lasers, laser, low level laser therapy (LLLT), light therapy, phototherapy, light-emitting dioide, visible light, and infrared.

• Patients were in the active antitumor treatment phase of care.
• The study has clinical applicability for pediatric applications.

A total of 692 papers initially were identified, and 24 clinical trials were included in the final review.

• Recommendations were laser therapy in a wavelength around 650 nm, intensity of 40 mW, and treatment of each square cm to tissue energy dose of 2 J/cm³ for prevention of oral mucositis in patients undergoing hematopoietic cell transplantation (HCT). For laser therapy as treatment, no guideline was possible because of insufficient evidence.
• No guidelines for LED and other light sources were provided because of insufficient evidence at the time, but promising findings noted that LED and visible light therapy appeared to interact with human tissue in the same way as LLLT.
• Laser therapy was recommended for prevention of radiation-induced oral mucositis in patients without concomitant chemotherapy with head and neck cancer.
• No guidelines were possible for combination radiation and chemotherapy because of inconsistent findings.
• No guideline were possible for other groups of patients.

• Multiple sources of evidence were relatively flawed studies.
• The authors noted later-breaking evidence that is promising in other groups but not fully included in the review.
• The review included articles through 2010 only.

Guidelines support use of LLLT for the prevention of oral mucositis in patients undergoing HCT and in patients with head and neck cancer receiving radiotherapy. The research in this area involves a variety of laser devices, protocols, and dosage, making it difficult to identify a specific protocol for clinical application. The most effective wavelengths and dosages are not yet clear. Most protocols examined have involved daily and long treatment times.  Based on accumulating evidence, LLLT or other forms of light therapy have the potential to become part of routine treatment.

The process began with a MEDLINE search of research articles from 2002–May 2005. Authors also examined abstracts from American Society of Clinical Oncology, American Society of Hematology, and the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology, as well as the bibliographies of the articles from the MEDLINE search. Articles were included if they involved the use of alternative or natural agents, ice, or laser therapy in the prevention and management of alimentary mucositis.

The initial search identified 167 articles. Of these, 14 were selected and reviewed. These involved one preclinical study on alternative/natural therapy, four clinical studies on cryotherapy, two studies on laser therapy, and seven studies on alternative and natural therapy. The studies were randomized, controlled, and determined to have a low bias potential.

The sample characteristics varied across studies.

Major and minor design flaws prevented the recommendation of scientifically based guidelines. Strong evidence exists for the use of cryotherapy in patients receiving high-dose melphalan (140 mg/m²) as part of the conditioning regimen for hematopoietic stem cell transplantation. Cryotherapy is not appropriate for use with agents with a longer half-life such as methotrexate or doxorubicin. Laser therapy seems promising.

To date, clinical studies with laser therapy have been small, protocols are not standardized, laser devices are different, parameters are varied, and assessment tools are not uniform.

The authors recommended further investigation of the agents and noted the lack of standardized assessment instruments.

To investigate the effect of a six-week intervention program including exercise, relaxation, massage, and body awareness training on anxiety and depression in patients undergoing chemotherapy

Patients were randomly assigned to the intervention group or a wait list control group. Patients in the intervention participated in group supervised exercise sessions for six weeks. Sessions involved fitness training on stationary bicycles of 10.5 metabolic equivalents (MET) and heavy resistance training. Warm up and cool down exercises and stretching were also done. All patients received usual care. Control group patients were not restrained from increasing physical activity and participating in available supportive care activities. Data on depression and anxiety were obtained at baseline and were repeated at week 6.

• The study reported on a sample of 209 patients.
• Mean patient age was 47.5 years, with a range of 20–65 years.
• The sample was 75% female and 25% male.
• Patients had a variety of tumor types; the most frequent were breast and bowel cancers.
• Most patients (71%) were married or living together in a relationship.
• About 17% had a usual activity level of “sedentary” at baseline, and 34% had baseline activity levels of regular physical exercise of at least three hours per week or more.
• Baseline HADS anxiety scores ranged from 0 to 19, and baseline HADS depression scores ranged from 0 to 14; 23.4% were identified as moderate for anxiety, and 11.5% were suspicious or definite cases of depression.

• Multisite
• Outpatient setting
• Denmark

Patients were undergoing the active treatment phase of care.

The study design was post-hoc analysis of data from a randomized controlled trial.

Hospital Anxiety and Depression Scale (HADS)

The intervention group depression score declined a mean of 0.7 points, compared to a decline of 0.24 points on average in the control group (p = 0.015). Patients defined by HADS as borderline or definite cases of depression (n = 24, HADS score ≥ 8) had a mean reduction of –2.53 points, while controls declined an average of 0.25 points (p = 0.021). There were no significant changes or differences between groups in anxiety scores either in the whole sample or in the subgroup defined as baseline borderline or moderate anxiety. Adherence to the exercise sessions was 73.1%.

Exercise may be helpful to reduce depression in patients receiving cancer chemotherapy. No effect on anxiety was observed.

• The study did not have an appropriate control group.
• There was no attentional control.
• Intervention participants worked in groups and had the opportunity for group discussion, etc., so it is unclear what aspects of this multicomponent program contributed to effects seen.
• There is no information about the activity level of control patients.
• No information is provided regarding the use of any medications for anxiety or depression.
• In the overall intervention group, mean score changes were below those identified as clinically relevant for HADs.
• Only 24 patients had baseline scores indicating probable depression, so analysis showing an effect for the intervention was only in a very small group.

Findings suggest that the intervention tested here, including exercise, group support, massage, and body awareness interventions, may be helpful to combat depression, but may not be helpful for anxiety. However, clinically relevant effects were only seen for depression in those patients who had clinically relevant levels of depression scores at baseline. This suggests that such a program may not be useful to prevent depression, but may be helpful in the situation of actual depression. Screening for depression may be useful to identify those individual patients who are most likely to benefit from this type of approach. Further research is needed to test whether combinations of pharmacotherapy, exercise, and psychotherapy are better than separate approaches to manage anxiety and depression.

To determine the effectiveness of a specific structured exercise intervention on patients undergoing chemotherapy

Patients with cancer who were undergoing chemotherapy volunteered to participate in the six-week structured exercise program. The total time of all weekly sessions was nine hours per week. Fitness training, relaxation, body awareness training, and high- or low-intensity programs were offered, and safety measures were incorporated. Participants were assessed for depression and anxiety at baseline and after the six-week intervention.

• The sample was composed of 91 participants.
• The participants were men and women receiving chemotherapy for various cancers. Of all participants, 70% were female.
• Participants self-referred for participation, after seeing posters and pamphlets in clinics.

• Multisite
• Denmark and Sweden

Prospective pre/post-test one-group design

• Hospital Anxiety and Depression scale, anxiety and depression subscales
• Maximal oxygen consumption test (VO₂ max test), to measure aerobic capacity

• Anxiety and depression scores decreased from baseline to six weeks. The decrease of depression scores was more moderate than the decrease of anxiety scores, but both were significant.
• Most participants had low levels of depression and anxiety at baseline.
• VO₂ max scores significantly increased over time. Improvements in VO₂ max scores were associated with improvements in depression but not anxiety.

• The study had a small sample size. The sample contained a disproportionate number of women. Patients self-referred to the study, and those patients may have been more motivated and psychologically intact than others.
• The study had a risk of bias due to no control group.
• Groups contained an unequal number of cancers and different cancer diagnoses.
• Investigators did not collect information about psychopharmacologic drug use. Such drugs could have influenced results.
• Levels of anxiety and depression were low at baseline.