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.

The intervention was a six-week, nine-hour weekly group intervention of high (exercise) and low (massage) intensity. “Talking time” also was included. A trained nurse and physiotherapist administered the intervention.

• The study reported on a sample of 91 patients.
• The sample was comprised of a heterogeneous cancer population receiving chemotherapy.

Denmark

A prospective follow-up design was used (one group, pre/post-test).

• Hospital Anxiety and Depression Scale (HADS) – depression and anxiety subscales
• Aerobic capacity

Anxiety and depression scores improved (p < 0.001). Patients who were physically nonactive improved more on the HADS anxiety subscale than those in the active group. Women improved more on the HADS anxiety subscale than men.

• The study was not randomized.
• The study did not include pharmacologic assessment.
• The sample was 70% female.

In cycle 1, 28 patients received irinotecan plus 1,000 mg oral-activated charcoal (AC) plus 25 ml water the evening before irinotecan and then three times per day for 48 hours after, on an empty stomach. In cycle 2, 24 patients received irinotecan without AC.

This study reported on 52 patients with advanced colorectal cancer receiving 125 mg/m² irinotecan weekly for four weeks with two weeks of rest.

This was a prospective, nonrandomized trial; patients served as their own controls.

• Patient diaries were used to record diarrhea frequency and grading using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) and daily loperamide use.
• Research nurses closely monitored compliance with the loperamide regimen (4 mg at first onset of delayed diarrhea and then 2 mg every 2 hours, 4 mg every 4 hours at night, until patient was diarrhea free for 12 hours) by inspection of provided diaries.

• Administration of AC with irinotecan in cycle 1 was associated with
  • Decreased grade 3 and 4 diarrhea
  • Decreased loperamide use
  • Increased irinotecan dose intensity.
• In cycle 1, 7.1% of patients recorded grade 3-4 diarrhea. In cycle 2, 25% of patients recorded grade 3-4 diarrhea.
• In cycle 1, 46.1% of patients recorded grade 0 diarrhea. In cycle 2, 20.8% of patients recorded grade 0 diarrhea.
• In cycle 1, 98% of patients received their planned doses. In cycle 2, 70% of patients received their planned doses.
• In cycle 1, 25% of patients received more than 10 loperamide cycles. In cycle 2, 54% of patients received more than 10 loperamide cycles.

Any statistical comparison in the efficacy parameters defined in the trial would be associated with large confidence intervals.

• The sample size was small.
• Patients acted as their own controls.
• Irinotecan dose reductions and supportive care are complex.

This was an exploratory trial with small patient numbers; results are hypothesis-generating and require additional confirmation in a larger study.

 To examine effects of a standardized cognitive-behavioral educational intervention on quality of life (QOL) of patients and their caregivers

Patients designated one caregiver as their coparticipant in the study. Dyads were randomly assigned to intervention or standard care control groups. Those in the intervention arm received a copy of The Home Care Guide for Cancer and participated in three educational sessions with a trained educator. The first session was up to seven days prior to or on the day of entry into a clinical trial. Two additional sessions were done within the next 30 days. Sessions were used to reinforce learning by focusing on patient- or caregiver-identified problems. Usual care was not described. Data were collected at baseline and at 30, 60, 90, 120, and 180 days.

• The sample included 441 patient/caregiver dyads, with 331 dyads in the intervention group. 
• Mean age for patients and caregivers was 61.5 years.
• The male sample was 44% patient and 31% caregiver; the female sample was 55% patient and 68% caregiver.
• Patients had various types of cancer, with the most frequent diagnoses being gastrointestinal, genitourinary, and thoracic cancers.
• All patients had advanced-stage disease and were enrolled in phase 1, 2, or 3 clinical trials.
• Of the caregiver sample, 49% worked full- or part-time, 55% provided four or less hours of care per day or week, 70% were spouses, 65% had college or graduate school education, and 29% had an annual income greater than $80,000.

• Mutlisite  
• Outpatient setting
• Multiple cancer centers in the United States
   

• Active treatment
• End of life and palliative care
   

A randomized controlled trial design was used.

• City of Hope Quality of Life Instrument    
• Social Problem-Solving Inventory
   

Approximately 25% of dyads in both groups withdrew from the study by their own choice. Among patients, there was a five-point decline (100-point scale) in QOL over six months, with no difference between study groups. Among caregivers, those in the control group had QOL scores decline more than those in the intervention group (p = 0.02), according to reported predicted decline from baseline. Caregivers did not show any significant changes in problem-solving skills over time in either study group. The intervention was associated with a slower rate of decline in spiritual aspect of the QOL measure. Caregivers overall showed a decrease in rational problem-solving skills over time, and there were no significant differences between groups, suggesting that the slower decline in  QOL with the intervention were not likely a direct result of improved problem-solving skills.

Findings show some potential benefits in the intervention group, but as pointed out by the authors, differences were not likely as a result of improved problem-solving skills, which was the emphasis of the intervention. The study does not demonstrate convincing effects of this intervention for caregivers.

• The study did not have an appropriate control group or attentional control. 
• The study sample had a relatively high drop-out rate.
• Several aspects of the report were confusing: Inclusion criteria stated that patients receiving chemotherapy or radiation therapy were excluded, yet all were on clinical trials involving some type of treatment intervention. Treatments received were not stated. There was no description of usual care for the control situation.
• The study had no blinding, so there was associated risk of bias.
• The statistical analysis used was a predictive model, apparently to enable analysis in the face of missing data; however, there was no description of how much missing data there was or the percent of attendance at sessions. Analysis attempts to compare actual findings in controls with predicted results in the intervention group are not reasonable. There was no direct statistical comparison between groups or examination of demographic differences between groups, which could be expected to affect results.
• The control group was much smaller than the intervention group, questioning power of analysis across groups.
• Subjects tended to be highly educated and in a higher socioeconomic group; findings may not be widely generalizable.

The study's drop-out rate suggests that this intervention may not be practical or acceptable because most of these were by individual participant choice. The study does not provide convincing evidence of effectiveness of this intervention on quality of life for patients or caregivers.