To compare the efficacy and safety of a pegfilgrastim biosimilar to reference pegfilgrastim

Patients were randomized to receive 6 mg of either reference pegfilgrastim or a biosimilar. The colony-stimulating factor (CSF) was given on day 2 of each cycle. ANC was measured on day 1 of cycle 1, then daily until recovery after nadir or until day 15. A margin of one day of neutropenia was established as the margin for noninferiority analysis.

• N = 275   
• MEAN AGE = 48.9 years
• FEMALES: 100%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Patients with breast cancer receiving docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy 

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: European countries

• PHASE OF CARE: Active antitumor treatment

• Noninferiority, randomized, controlled trial

• Consecutive days of neutropenia 
• Depth of absolute neutrophil count (ANC) nadir
• Days to ANC recovery
• Infections

All study outcomes were similar in both groups. Over 95% of both groups had musculoskeletal adverse events, including bone pain, myalgia, arthralgia, and back pain (13.7%–16.1% of patients).

The CSF biosimilar evaluated here demonstrated similar efficacy and safety to that of the reference pegfilgrastim.

Pegfilgrastim and the CSF biosimilar evaluated were shown to be therapeutically equivalent.

To determine if acute exercise reduces state anxiety in breast cancer survivors

Participants recruited were randomly assigned to a light or moderate intensity group and were asked to complete both moderate and light intensity exercise on two different days. Exercise sessions were done by cycling. Prior to exercise, questionnaires for anxiety and self-efficacy were completed. Participants cycled for 20 minutes, staying with standardized heart rate ranges as defined for light and moderate intensity. Questionnaires were repeated after each exercise session following an eight-minute rest.

• The study reported on a sample of 50 participants: 25 breast cancer survivors and 25 age-matched women without a cancer diagnosis.
• Mean participant age was 59 years in the breast cancer survivors and 56 years in the other women.
• Average time since diagnosis of breast cancer was five years.
• Of the sample, 40% had at least a bachelor’s degree and 80% were married or living with a partner.

• Single site
• Canada

The study has clinical applicability for late effects and survivorship.

A randomized, experimental, repeated-measures design was used.

• Spielberger State Anxiety Short Form
• Self-efficacy questionnaire adapted from a previous study: A total efficacy score was calculated by summing confidence ratings by the respondent within a possible score of 100 (reliability – 0.91).

There were no differences between day 1 and 2 for anxiety and self-efficacy. Repeated measures ANOVA on anxiety showed a main effect for time (p < 0.01), with anxiety decreasing across the time of exercise. The intensity of the exercise was not significant. There were no differences between breast cancer survivors and others. Self-efficacy measures showed a main effect for time (p < 0.01), but no differences between breast cancer survivors and others or between exercise intensities. Breast cancer survivors and others reported similar pre-exercise state anxiety levels. There was a significant reciprocal relationship between self-efficacy and state anxiety both pre- and post-exercise (p < 0.05).

Exercise appears to have a short-term effect in reducing anxiety and increasing perception of self-efficacy.

• The study had a small sample, with less than 100 participants.
• The study did not include control observations.
• The study period and intervention was very brief, consisting of only two days of exercise and observations.
• Utility of findings is questionable.
• Participants were generally physically fit and may have been biased toward exercise, limiting applicability of findings.

Studies with longer-term exercise interventions and in participants with higher levels of anxiety may be helpful in exploring these issues. Long-term findings suggest that the specific approach to management of anxiety during the cancer diagnostic phase does not appear to significantly impact anxiety and depression in women with low-risk abnormal findings. The timing of depression might suggest that extended follow-up after diagnostic testing and treatment may be associated with depression for some women. Which of the strategies examined here offer the best balance between benefits and harms is a matter of continuing debate.

The primary aim was to evaluate the safety and efficacy of modafinil in improving cancer-related fatigue (CRF) in patients with cancer.

The secondary aim was to assess the effect of modafinil on depression, quality of life (QOL), functional status, and cognitive function.

After initial assessment for all outcome measures, patients were treated with self-administered modafinil at an initial dose of 100 mg per day during weeks one to two. During weeks three to four, the dose was increased to 200 mg per day. All study parameters were reassessed at week two and at week four (completion of the trial).

• Twenty-seven patients were enrolled, and 19 completed the study.
• Average age was 60 years.
• Of the participants, 37% were male and 63% were female.
• Eastern Cooperative Oncology Group (ECOG) Performance: ECOG 1 was 37%; ECOG 2 was 44%; and ECOG 3 was 19%.

This was an open-label pilot study.

• Primary Aim: Brief Fatigue Inventory (BFI)–Fatigue
• Secondary Aim
  • Cognitive Measures
    • Hopkins Verbal Learning Test (HVLT)—assessed verbal learning and memory
    • Grooved Pegboard Test—fine motor ability and hand-eye coordination
    • Controlled Oral Word Association Test (COWAT)—verbal fluency
    • Trail Making Test (TMT) Parts A & B—visual attention, motor speed, and cognitive flexibility
  • Other Measures
    • Hospital Anxiety and Depression Scale (HADS)—depression
    • Functional Assessment of Cancer Therapy-Brain (FACT-BR)—QOL
    • Barthel Index—functional status
    • ECOG—performance status
    • National Cancer Institute (NCI) Common Toxicity Criteria (CTC), version 2.0––scored severity of detected side effects

BFI was improved at two weeks for 46% of participants, and at four weeks, 75% had a significantly improved score (p = 0.025). FACT-BR showed an improvement in all subsets of well-being except social/family at two and four weeks (p < 0.05). HADS score declined significantly at two and four weeks (p < 0.001). Cognitive function was not significantly changed, except TMT-B showed a trend for an overall improvement. Functional status (Barthel Index) did not change, but overall performance status (ECOG) improved, with 40% of patients improving at least one level. Most side effects were mild. Side effects seen were dizziness, nausea, diarrhea, and heartburn.

Modafinil use was associated with improvement in fatigue, depression, and QOL measures and was well tolerated.

• The study had a small sample size, with an almost 30% drop-out rate.
• The study was an open-label design pilot study.
• No control comparison was included.

To evaluate the effects of a psychosocial support intervention on health-related quality of life (QOL) and fatigue.

Participants were randomized to an intervention or usual care control group. The intervention consisted of education sessions mixed with exercise, relaxation training, massage, qigong, visualization, and social activities, such as concerts and museum and restaurant visits. As reported in a previous pilot study, participants were residents at a spa-type facility during the intervention. The intervention was provided by an interdisciplinary group comprising physicians, psychologists, an art therapist, a massage therapist, a dietician, social workers, and a trained qigong provider for seven days. Follow-up was performed at two, six, and 12 months. Participants in the usual care control were only provided follow-up data collection.

• In total, 360 participants (100% female) were included.             
• Mean age was 58 years (range 30–84).
• All participants had breast cancer. Most had undergone breast-conserving surgery and had received or were receiving radiation therapy.
• Of the participants, 53% were married.

• Single site  
• Inpatient   
• Sweden

• Participants were undergoing the transition phase after active treatment.
• The study has clinical applicability for elderly care.

The study was a randomized, controlled trial.

• Swedish version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), including the 23-item breast cancer module
• Fatigue Questionnaire, Swedish version

Fatigue scores were similar in both groups and declined over time up to 12 months in both groups. There were no differences in fatigue levels over time between the groups. There were no significant effects of the intervention on QOL measures.

The multimodal intervention demonstrated no significant effect on QOL or fatigue.

• The study had risks of bias due to no blinding, no appropriate attentional control condition, and the sample characteristics.
• The findings were not generalizable.
• The intervention was expensive, impractical, and required training.
• Participants tended to self-select for involvement. 
• This type of week-long stay and set of interventions can be expected to be expensive.

The specific approach providing a multifaceted, psychoeducational type of intervention was not shown to affect fatigue or QOL in women with breast cancer. The most effective content, duration, and frequency of psychosocial and multimodal support interventions were not clear.

Long-term follow-up to evaluate quality of life after support group intervention in a randomized group of women with primary breast cancer presenting for postoperative radiotherapy.

The current study is a long-term follow-up 5–9 years after randomization into groups. The intervention and control groups were stratified by chemotherapy or nonchemotherapy treatment. The intervention was a one-week support group with four days of follow-up two months postintervention during residential care at the Foundation of Lustgården Mälardalen. The intervention involved lectures and group discussions about the etiology of cancer, risk factors, treatment, physical and psychological effects, and coping strategies. Patients engaged in physical exercise, relaxation, Qigong, and nonverbal communication exercises, as well as art and dance therapy. All participants completed questionnaires at baseline and follow-up questionnaires at 2, 6, and 12 months postintervention. The control group participated only in routine follow-up at the Department of Oncology or the Department of Surgery.

• N = 382 (final sample); 191 in intervention group and 191 in control group
• AGE RANGE: 30–83
• MALES: 0 %, FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Patients were newly diagnosed with primary breast cancer at the beginning of the parent study.

• SITE: Single site    
• SETTING TYPE: Outpatient   
• LOCATION: Department of Oncology at the Central Hospital in Västeräs, Sweden

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

• Prospective randomized trial
  • Long-term follow-up comparison of test scores at baseline, 12 months, and at end

• Hospital Anxiety and Depression Scale (HADS)
• European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
• European Organisation for Research and Treatment of Cancer Breast Cancer-Specific Quality of Life Questionnaire (QLQ-BR23)
• Fatigue Questionnaire (FQ)

Fatigue symptoms improved over time, which was a significant finding in the intervention and control groups. Being upset about hair loss improved over time in the intervention group. High anxiety scores improved over time and were not significantly different between the two groups in long-term follow-up. Depression scores were high at follow-up for seven women in each group, and no significant difference was found at baseline and postintervention, adjusting for covariates. Neither group showed improvement between the 12-month follow-up and long-term follow-up. 

Effects of support group intervention may provide a sense of security that can fade over time, reversing improvements in anxiety and depression. Treatment-related fatigue may improve over time. Significant improvement was found in cognitive function, body image, and future perspective, but no significant effect was found on levels of anxiety and depression.

• An average of 6.5 years elapsed between the parent study and the follow-up study.
• Participants were lost to follow-up between the parent study and the follow-up study.
• No initial need for an intervention was conducted.

Women who have received chemotherapy have greater symptom severity and may benefit more on global health and cognitive function fatigue, when compared to women who have not received chemotherapy. Additional research is needed to evaluate the influence of exercise and psychosocial support interventions, according to patient needs for content, duration, and an assessment of spiritual well-being using the Functional Assessment of Chronic Illness Therapy (FACIT).

To evaluate the effect of a support program on anxiety and depression in patients with breast cancer

The intervention was a weeklong multidisciplinary residential program. The intervention took place within four months after the end of tumor treatment and ran for seven days, followed by four days of follow-up two months after the initial visit. The team consisted of oncologists, social workers, art therapists, massage therapists, a dietitian, and a mindfulness practitioner.

• The study reported on a sample of 382 female patients with breast cancer; 309 completed the 12-month follow-up.
• Mean ages in the treatment group were 54 years (range = 30–69) and 61 years (range = 34–84).
• Mean ages in the control group were 55 years (range = 38–70) and 62 years (range = 38–83).
• Patients were subgrouped into whether they had chemotherapy or not. Patients had either breast-conserving surgery or mastectomy. Those with breast-conserving surgery or lymph node involvement also received radiation therapy.

• Single site
• Retreat center setting
• Sweden

• Transition phase of care
• Late effects and survivorship

A randomized controlled trial design was used.

Hospital Anxiety and Depression Scale (HADS)–Swedish version

After 12 months, 10% in the intervention group versus 19% in the control group had a high anxiety score (p = 0.055).

Support group intervention including education about the disease and psychological reactions, mixed with art and dance therapy, qigong, and relaxation, was shown to positively influence anxiety levels among patients with breast cancer over time, whereas depression levels were unaffected by the intervention.

• A variety of interventions and providers were used, limiting the ability to transfer the findings to other venues.
• Reproducibility is an issue.
• The study had no appropriate attentional control.

Because of costs and time constraints, the ability of this program to be replicated is suspect. The particular components of the program that provided the most effectiveness were not analyzed and therefore cannot be reproduced or further studied.

Review the effects of low level laser therapy (LLLT) in prevention and treatment of oral mucositis induced by cancer therapy. Meta-analysis was done, and all results are provided.

Databases searched were Medline, EMBASE, CINAHL, PedRo, and Cochrane Controlled Trial Register. Hand searching in physiotherapy and medical journals from several countries also were used.

Search keywords were low level laser therapy, low intensity laser therapy, low energy laser therapy, phototherapy, oral mucositis, cancer, chemotherapy, radiation therapy, and specific laser types.

Studies were included if they

• Involved patients with cancer who had been diagnoses with oral mucositis after chemotherapy or radiation therapy.
• Used treatment with laser therapy with wavelengths of 632–1064 nm.
• Incorporated a randomized parallel group or crossover design, with blinding and placebo control with identical placebo laser.

A total of 149 papers were initially retrieved. Literature was evaluated using the Jadad checklist and inclusion of study funding sources.

A final sample of 11 trials published from 1997–2009 included 415 patients. Samples ranged from 21–70 subjects and included those receiving chemotherapy, radiation therapy, combined therapy, and transplant cases. One study was done in children.

• Six trials involved prevention of OM. The overall effect size was 2.31 in favor of laser (p = 0.02). In one trial, which used less than 1 joule, results did not favor laser use. Subgroup analysis showed positive results with laser whether done before cancer therapy, before and during therapy, or during therapy.
• Five trials assessed duration of OM. Overall effect size was 8.35 in favor of laser therapy (p < 0.00001).
• Seven trials assessed severity of OM. Overall effect size was 4.01 in favor of laser (p < 0.00001). Subgroup analysis showed there was no significant difference in these findings with different wavelengths of infrared LLLT.
• Three trials studied the effect on pain. Effect size was 4.97 in favor of laser (p < 0.00001).
• All analyses showed substantial heterogeneity. LLLT was well tolerated with no serious incidents or withdrawals because of the LLLT treatment.

Moderate to strong evidence was found for effectiveness of LLLT in the prevention of OM, reduced duration and severity of OM, and reduced pain with doses of 1–6 joules per point. Trials aimed at prevention started LLLT seven days before cancer treatment regimens, and effective dosing seen ranged from 1–6 joules. This meta-analysis supported the effectiveness of LLLT in the dosage ranges reported here for the prevention and management of oral mucositis.

The quality of studies was determined to be high; however, substantial variation existed in the actual treatment procedures, number of treatments, timing of treatments, and heterogeneity in the overall findings.

To examine the effects of Withania somnifera (WS) on fatigue and quality of life among patients with breast cancer receiving chemotherapy

WS was supplied as a powder in 500 mg capsules. Patients was asked to take four capsules three times daily for total daily dose of 6 g. Patients were followed for six cycles of chemotherapy. Study measures were conducted at baseline and periodically through treatment. Some measures were conducted on the first day of every cycle, and others were conducted on the first day of cycle 1, 3, and 6. Consecutive patients were alternately assigned to treatment or usual care groups.

• N = 100  
• MEAN AGE = 50.75 years (range = 32–72)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All had breast cancer. Chemotherapy was done as either adjuvant or palliative treatment. Most patients had stage II or III disease. Patients were either on regimens of cyclophosphamide, epirubicin, and 5FU, or taxotere, adriamycin, and 5FU.

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

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS: Palliative care 

• Non-random, open label, two-group comparison

• Piper Fatigue Scale
• Schwartz Cancer Fatigue Scale
• EORTC QOL-C30

Several QOL measures were significantly better in the treatment group compared to controls: physical functioning (p < .001), role functioning (p < .001), insomnia (p < .001), loss of appetite (p = .011), emotional functioning (p < .001), and social functioning (p < .001). Fatigue scores were significantly better as shown by repeated measures ANOVA in the intervention group (p ≤ .003). Ninety-eight percent of intervention patients found the intervention acceptable.

Findings suggest that the herbal treatment of WS is beneficial for the management of fatigue in patients with breast cancer undergoing chemotherapy.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Other limitations/explanation: No information on adherence to the WS regimen; therefore, it is unclear if patients took all of the substance as planned. At baseline, the control group had significantly lower QOL scores.

The herbal treatment of WS, which has been used in Ayurveda medicine, may be beneficial to reduce fatigue in patients with cancer. This particular study has several important limitations; however, results are promising. Additional well-designed research with this herbal remedy is warranted.

To assess the association between palliative care management, symptoms, and quality of life

Clinical records of patients referred for outpatient palliative care who had follow-up visits within 120 days of initial referral were included. Retrospective analysis of clinical data was done.

• N = 266
• MEAN AGE = 57.2 years (SD = 13.8 years)
• MALES: 46%, FEMALES: 54%
• KEY DISEASE CHARACTERISTICS: 59% had metastatic disease. Multiple cancer sites were included, and 68% were on active treatment. Median time since diagnosis was 17 months. Mean time of follow-up after initial visit was 41 days.

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

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

• Retrospective, descriptive

• Edmonton Symptom Assessment Scale

At the time of initial visit, average symptom scores were 2.9–5.8 (10-point scale). At the first follow-up visit, there was an average 0.67-point improvement in pain (p < .001), a 0.67-point improvement in fatigue (p < .001), a 0.94-point improvement in depression (p < .001), and a 0.89-point improvement in anxiety (p < .001). At least 50% of patients reported a greater than one-point improvement in symptoms by the first follow-up visit, and 16%–25% reported a one-point or greater worsening of symptoms. Among 142 patients who had a second follow-up visit, there was continued significant improvement from baseline symptom scores. Patients on active treatment had less improvement in fatigue than others (p = .02).

Most patients who continued follow-up by palliative care demonstrated improvement in pain, fatigue, anxiety, and depression.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias (sample characteristics)
• Other limitations/explanation: The study only included those patients referred who had follow-up visits in the palliative care clinic. It is possible that at least some of those who did not come back for another visit did not have symptom improvement, so results may be overestimated. The opposite also is possible. There was a lot of variability in the timing of follow-ups. A single symptom measure was used repeatedly; it is possible that the study had threats to validity because of testing effect and patient expectations. It is not known if oncologic providers made any changes in medications for symptom management, as palliative care follow-up visits were relatively infrequent.

Palliative care, with attention to symptom management, has been shown to be effective in reducing symptom severity for the majority of patients. It is not clear, however, if formal palliative care services result in better outcomes than attention to symptom management in general. It would be expected that, whether provided by oncology or palliative care providers, focused attention on symptom management would result in improvement of symptoms. The optimum frequency of follow-up and timing for optimal symptom control has not been determined.

To examine the effects of Reiki on pain, anxiety, and global wellness among patients with cancer who are receiving chemotherapy

Reiki sessions were offered to patients in a day oncology and infusion services unit that provided chemotherapy. Patients sat in a chair or lay on a bed during Reiki sessions. Each session lasted approximately 30 minutes. Each patient received a maximum of four Reiki sessions. Prior to each session, Reiki practitioners assessed levels of anxiety and pain according to a numeric scale. After each session, levels of pain and anxiety were recorded on a visual analog scale. The study was done over three years.

• The study reported on a sample of 118 patients, but only 22 completed all sessions.
• Mean patient age was 55 years, with a range of 33–77 years.
• The sample was 57% male and 43% female.
• Patients had various types of cancer, and all were receiving chemotherapy.

• Single site
• Outpatient setting
• Italy

Patients were receiving active antitumor treatment.

A prospective pre/post-test design was used.

• Numeric rating scale
• Visual analog scale (VAS)

Only 48% of patients had more than one Reiki session, and only 22 patients (17%) completed four sessions and were included in statistical analysis. From session 1 to session 4, mean anxiety scores post-Reiki session declined, but scores immediately after each time point were higher than those reported immediately prior to the session.

Findings of this study do not support the effectiveness of Reiki. The study included numerous limitations in study design and methods.

• The study had a small sample size, with fewer than 30 participants.
• The study had risk of bias due to no control group, no blinding, and no random assignment.
• Measurement validity/reliability was questionable.
• The intervention was expensive, impractical, or presented training needs.
• The study reported that pre-session measures, on a numeric scale, were collected by Reiki providers and that post-session measures, per a VAS, were collected by the practitioner. These are two different scales that cannot be directly compared. The study does not make clear what the actual data scale was or the size of the VAS, for interpretation of data.
• Scoring was done by the Reiki practitioners, which could introduce bias. Reiki practitioners required two years of training, one year of additional workshops, and one year of in-hospital practice with tutors.

 This study does not support the effectiveness of Reiki. The study and methods were not well designed or reported.