RESOURCE TYPE: Evidence-based guideline

PROCESS OF DEVELOPMENT: Development according to NICE recommendations. An international expert group identified clinical priorities and questions to scope literature reviews. The draft was made available for public input. GRADES was used to identify the level of evidence and formulate draft recommendations. Consensus on recommendations was obtained using a Delphi technique. The specifics of the literature search strategy are not provided.

No information about results of literature searching are provided.

• Cannabinoids may increase appetite in selected patients, but there is insufficient overall evidence to support their use.
• Progestins seem to stimulate appetite and increase body weight. Progestins should be considered for patients with anorexia.
• Steroids may be beneficial for stimulation of appetite; however, they should be used for short periods, with a maximum of two weeks.

There was limited reporting and no summary of the evidence base for recommendations in this document.

This review provides weak evidence that shows no support for use of cannabinoids to improve appetite in patients with cancer. Individual patients may report some benefit of cannabinoids in terms of appetite, but there is no real evidence to support efficacy for this symptom.

To assess the efficacy of non-hormonal interventions for the treatment of hot flushes in women with a history of breast cancer

TYPE OF STUDY Combined systematic review and meta analysis

• DATABASES: CENTRAL, CINAHL, PsycINFO, LILACS, MEDLINE, EMBASE, WHO clinical trials registry combined with hand search of reference lists of reviews, included articles, conference proceedings and contacts with experts.
• KEYWORDS:  Detailed key words by database listed in appendix - all included randomized controlled trials of therapies for vasomotor symptoms (hot flashes, night sweats) in women with breast cancer
• INCLUSION CRITERIA: Randomized controlled clinical trials of non-hormonal interventions pertaining to women of any age experiencing hot flashes and with or without a history of breast cancer.  Studies that included women without a history of breast cancer were accepted if data on these cases was presented separately or if these women constituted <20% of the study population  
• EXCLUSION CRITERIA: Studies of hormonal interventions and hormone-like interventions including plant phytoestrogens, black cohosh, and tibolone
• METHOD OF STUDY EVALUATION: Evaluated studies according to the Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2; Two persons evaluated each study and extracted information about the studies onto forms; Bias in studies was assessed and noted.
   

TOTAL REFERENCES RETRIEVED : N =1012

• FINAL NUMBER OF STUDIES INCLUDED: N = 16    
• KEY SAMPLE CHARACTERISTICS: All women with breast cancer and reporting vasomotor symptoms. There were inconsistencies in inclusion criteria related to number or severity of hot flashes required for inclusion.

APPLICATIONS Late Effects and Survivorship

• Outcomes inconsistently reported across studies 
• Outcomes included hot flash frequency, severity, bother, interference, hot flash composite scores (frequency x severity). 
• Secondary outcomes were also inconsistently reported and included side effects, recurrence risk, and health-related quality of life

• Clonidine is effective but may have intolerable side effects.
• Gabapentin and SSRIs/SNRIs may be effective but must be weighed against side effects, cost, dosing, and absolute benefit.
• Vitamin E should not be recommended as it was not effective.
• Evidence for other non-pharmacological therapies is limited.

To evaluate the effectiveness of treatments for several cutaneous reactions.

Rash was treated with erythromycin 4% gel, phosphate clindamycin 1.2 g and oil 100 g in cream BID, and oral doxycycline 100 mg daily for two months. Patients with grade 2 or 3 pruritus were treated with antihistamines (e.g., cetirizine). Finally, xerosis was treated with topical antibiotic ointments, soap substitutes, bath oil, and moisturizing emollients.

The study reported on a sample of 34 patients with metastatic colorectal cancer who were receiving cetuximab and irinotecan.

The trial was conducted at two sites in Italy.

This was an open-label, uncontrolled phase 2 trial. A series of cases with significant dermatologic events (DEs) was described, and management of DEs was discussed.

• Skin toxicity was evaluated with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0
• Efficacy was evaluated locally according to the Response Evaluation Criteria in Solid Tumors (RECIST) system.

Rash:

• Twenty of 32 patients (63%) developed a rash characterized by a pustular papular erythematous eruption.
• Onset of eruptions was one to three weeks after therapy initiated.
• In some cases, the investigators observed diffuse erythema with follicular papules and pustules.
• A degree of hyperpigmentation was noted in some patients.
• Bacterial cultures were performed when infection was possible, and no secondary infection appeared concomitantly in the patients.
• Topical antibiotic therapy was performed until resolution of skin toxicity.
• Seven patients required oral doxycycline 100 mg daily for two months.

Pruritus:

• Antihistamines provided relief for patients with grade 2 or 3 pruritus.

Xerosis:

• Xerosis was observed in 16 patients (50%).
• After six to eight weeks of treatment, some patients developed scaly, dry, itchy skin in areas previously affected by the acneform eruptions.
• Topical antibiotic ointments, soap substitutes, bath oil, and treatment with moisturizing emollients controlled the symptoms well.

Interventions were effective in resolving the dermatologic effects of cetuximab and irinotecan.

• This was an uncontrolled, nonrandomized trial.
• A combination of interventions was used; therefore, determining the effectiveness of the individual interventions is difficult.
• The authors stated that no established guidelines exist for the treatment of skin toxicities associated with epidermal growth factor receptor–inhibitor (EGFRI) therapy. Interventions were based on expert opinion.

To assess the feasibility, acceptability, and preliminary effects of a 12-week combined physical activity and relaxation intervention for sedentary, early stage breast cancer survivors after completing all primary treatment.

Early stage breast cancer survivors participated in a 12-week combined physical activity (PA) and relaxation intervention, with baseline and 12- and 24-week assessments. Participants received a theoretically grounded intervention modeled after on the “Moving Forward” intervention based on the principles of the transtheoretical model (TTM) and the social cognitive theory (SCT). Participants were instructed to do moderate-intensity level exercise with pre-/post stretching. The goal was to walk 30 minutes five times a week by the twelfth week of the intervention. The relaxation component included instruction on progressive muscle relaxation (PMR); a CD with PMR instructions was included. Participants were telephoned weekly to provide counseling, a review of their practice activities, reinforcement, identification of barriers, and negation of the next week's goals.

• The sample was comprised of 23 women.
• Mean age was 52.5 years (standard deviation = 8.4 years).
• Most participants were diagnosed with stage I or II, nearly two years prior.
• The majority were partnered, white, and non-Hispanic.
• The sample was relatively well-educated, with most participants receiving at least some college education.

• Multisite
• Outpatient oncology clinics
• East coast, United States

• Patients were undergoing the long-term follow-up phase of care.
• The study has clinical applicability for late effects and survivorship.

The study used a prospective, single-arm, repeated measures design.

• Medical and demographic information obtained from self-report and medical record abstraction
• Seven-Day Physical Activity Recall (7-Day PAR)    
• Pittsburgh Sleep Quality Index (PSQI)
• Stage of Motivational Readiness for PA
• IM Systems-3 dimensional accelerometers (Biotrainer-Pro)
• Profile of Mood States (POMS)
• Intervention feasibility and acceptability assessed via a single item, 1–5 Likert score of satisfaction with the exercise portion of the program; or relaxation component

Participant evaluations of the intervention indicated that it was feasible and acceptable (e.g., 100% would recommend it to others); objective data further supported its feasibility (e.g., 83% completed the trial, and 91% of the intervention calls were received). In addition, when comparing 12- and 24-week follow-up data to baseline data, participants demonstrated significantly increased PA, improved mood and sleep quality, and reduced fatigue (p < 0.05).

The pilot study suggested that the intervention is feasible, acceptable, and produces promising effects on mood, sleep, and fatigue.

• The study had a small sample size, with less than 30 participants.
• The study lacked a control group.
• The sample was racially and socioeconomically homogenous.
• The eligibility criteria were conservative.  

Multibehavior interventions, such as exercise and relaxation, hold promise for cancer survivors and may improve quality of life (i.e., fatigue, sleep, mood, and disturbance).

To assess the feasibility, acceptability, and preliminary effects of a 12-week combined physical activity and relaxation intervention for breast cancer survivors.

Participants met with an intervention coordinator to complete baseline questionnaires and an activity assessment. They were then provided with exercise education about types of exercise and stretches, using a pedometer, setting activity goals, progressive muscle relaxation, and how to record these activities. Participants were then called weekly for 12 weeks during the intervention to provide further counseling.

• The sample was comprised of 19 women.
• Mean age was 52.5 years.
• Participants had breast cancer stage 0 to II.
• Participants had completed cancer therapy and were considered sedentary (moderate activity less than twice weekly or vigorous activity less than once weekly).
• Of the participants, 95.7% were white.

• Multisite
• Oncology clinics

• Participants were undergoing the long-term follow-up phase of care.
• The study has clinical applicability for late effects and survivorship.

The study used a pre-/post design.

• Intervention feasibility was assessed using single-item, 1-to-5 scale, not a standard instrument.
• Seven-day Physical Activity Recall (7-day PAR)
• The Stage of Motivational Readiness for Physical Activity
• IM Systems–three accelerometers (objective measure of physical activity) 
• Profile of Mood States (POMS)
• Pittsburgh Sleep Quality Index (PSQI)

Fatigue was statistically reduced from baseline to weeks 12 (p < 0.05) and 24 (p < 0.01). Sleep quality was also improved from baseline to weeks 12 (p < 0.01) and 24 (p < 0.05).

Participants found the intervention feasible without interrupting their levels of physical activity. Fatigue and sleep quality were improved significantly from baseline, suggesting a benefit from physical activity and relaxation as a combined practice. Further research is needed with control groups.

• The study lacked an appropriate control group.
• The study had a small sample size, with less than 30 participants.

Behavioral interventions for breast cancer survivors are a feasible and safe practice and may improve quality of life in participants. These interventions can be taught by nurses to patients.

To review the literature and define clinical practice guidelines for use of cytokines and growth factor agents for the prevention or treatment of oral mucositis from chemotherapy or radiation therapy in patients with various types of cancer receiving radiation, chemotherapy, or hemapoietic stem cell transplant (HSCT)

In this evidence-based guideline, two independent reviewers scored level of evidence by Somerfield and Hadorn criteria. Following panel consensus, findings were integrated into guidelines.

Databases searched were Ovid, MEDLINE, and hand searching.

Search keywords included all types of cytokines and growth factors.

Inclusion and exclusion criteria were not specified.

Patients were undergoing the active antitumor treatment phase of care.

Out of 1,718 papers that were initially retrieved, 64 studies were included in the systematic review.

Palifermin 60 mcg/kg/day for three days prior to conditioning and three days post-transplantation was recommended in patients receiving HSCT. No guideline was possible for palifermin use in other patient types. For granulocyte colony-stimulating factor (G-CSF), no guideline was possible. No guidelines were possible for granulocyte macrophage colony-stimulating factor (GM-CSF) mouthwash, topical transforming growth factor beta, mil-derived growth factor, epidermal growth factor, interleukin-II, ALT 104, or recombinant human intestinal trefoil factor.

Very limited research has been done in children. Guidelines do not specify if recommendations are for adults and children. Most studies had relatively low levels of evidence. Sample sizes were not reported.

Use of palifermin for mucositis prevention in HSCT recipients was recommended.

The purpose of the article is to examine whether prophylactic administration of IV immunoglobulin (IVIG) reduces mortality, major infections, and the rate of documented microbial infection in patients with lymphoproliferative and plasma cell disorders.

The PubMed, Cochrane Library, and LILACS databases as well as numerous conference proceedings published from 2002–2008. Hand searching of references was also done.

Key words were immunoglobulins, gammaglobulins, specific gammaglobulins names, hematologic neoplasms, or hematologic malignancies, multiple myeloma, plasma cell dyscrasias, leukemia, lymphoma or lumphoproliferative disorders.

Inclusion criteria:

• Randomized, controlled trials comparing an IVIG preparation with placebo, no treatment, another immunoglobulin preparation, or a different administration schedule or dose
• Patients with non-Hodgkin lymphoma, chronic lymphocytic leukemia, hairy cell leukemia, cutaneous lymphomas or Hodgkin lymphoma, monoclonal gammopathy, multiple myeloma, amyloidosis, Waldenstrom macroflobulinemia, cryuglobulinemia, or heavy chain disease.
• Any publication type
• Any language

The search strategy identified 613 trials. Trials were graded according to allocation concealment according to the Cochrane Handbook guidelines. Sixteen trials were considered relevant and included in the initial review. Seven of these were excluded due to duplication, route of administration, and study design.

The final sample included in the systematic review was nine studies. Five studies had usable information for meta analysis. Study samples ranged from 16–42, and the review included a total sample of 408 patients across all studies.

• Only two trials reported all cause mortality at one year, and both showed no difference between study groups.
• There was a statistically significant reduction in occurrence of major infection (RR = 0.45, 95% CI [0.27, 0.75])
• There was a significant, 51% reduction in all clinically documented infections with IVIG (RR = 0.49, 95% CI [0.39, 0.61])
• Polyvalent IVIG was associated with a significant increase in adverse events (RR = 2.37, 95% CI [1.74, 3.24]). Side effects included allergic reactions with anaphylaxis, fever, chills, and gastrointestinal complaints. Adverse events rarely required discontinuation of treatment.

Use of IVIG did not appear to affect overall mortality. The rate of major infections requiring inpatient treatment was significantly lowered by IVIG prophylaxis.

• Reviewed studies were old, done in the 1990s and since that time patient populations and therapeutic protocols have changed. 
• Implications of these findings in the context of current clinical practice are unclear.
• Different trials used different IVIG preparations from various companies, and varied doses were used. 
• These differences could have affected the comparison of trial outcomes in this meta-analysis.

Based on these results, contemporary studies of IVIG prophylaxis are warranted.

To investigate, critically appraise, and rate the evidence regarding agents used for the prevention of mucositis in children

Databases searched included CINAHL, Cochrane library, Ovid MEDLINE, PubMed, BioMed Central, and other internet-based sources. A total of 19 databases were searched.

Search keywords were mucositis, stomatitis, oral inflammation, mouth mucosal inflammation, prophylaxis, management, and prevent; in addition to keywords to identify children and all types of cancer therapy.

Studies were included in the search if they

• Involved English-speaking children.
• Were clinical trials conducted on the prevention of oral mucositis during cancer therapy.

Studies were excluded if they

• Were not in English
• Did not involve children
• Involved only gastrointestinal mucositis.
• Involved treatment of mucositis rather than prevention.
• Were case studies or pilot studies.
• Were commentaries or letters to the editor.
• Involved sample sizes of less than 20 patients.

• The total number of references retrieved was 16,471.
• The authors evaluated the references using the Canadian Task Force on Preventive Health Care evidence-based guidelines.

• The final number of studies was 27. The sample range across studies was not reported.
• Other than inclusion of pediatric cases, no other characteristics were described.

• Patients were undergoing the active antitumor treatment phase of care.
• The study has clinical applicability for pediatrics.

• The studies involved the following interventions.
  • Oral care protocols (n = 5)
  • Chlorhexidine mouthwash (n = 7) 
  • Benzydamine mouthwash (n = 1)
  • Iseganan mouthwash (n = 1),
  • Granulocyte macrophage-colony stimulating factor (GM-CSF) mouthwash (n = 2)
  • Oral glutamine (n = 2)
  • Enteral glutamine (n = 1)
  • Oral propantheline and cryotherapy (n = 1)
  • Oral cryotherapy (n = 1)
  • Oral sucralfate suspension (n = 1)
  • Prostaglandin E2 tablets (n = 1)
  • Chewing gum (n = 1)
  • Laser therapy (n = 3). 
• Good evidential support was found for the use of oral care protocols. Fair support was found for the use of chlorhexidine with some mixed results.
• Only one article was found that studied benzydamine, CSF, and iseganan. The evidence was deemed insufficient to make a recommendation. 
• Good evidential support was found against the use of sucralfate and prostaglandin E2 tablets.
• Evidence regarding laser use and oral and enteral glutamine were mixed.

The authors concluded that oral care protocols should be used; oral sucralfate suspension, prostaglandin E2, and GM-CSF mouthwash should not be considered based on current evidence; and chlorhexidine (without use as part of an oral care protocol), laser therapy, and glutamine should not be considered because of conflicting evidence.

• No disease or treatment factors were reported or considered in the analysis. 
• Some interventions were evaluated in only one study.
• The quality of the evidence in general was highly variable.
• No information was provided on how the outcome for mucositis was measured in the included studies.
• The authors recommendations suggest no use of a specific intervention if findings were conflicting, which assumes that insufficient evidence of effectiveness is equivalent to ineffectiveness.

Findings provide further support for use of oral care protocols. Results provided no other useful recommendations for preventive therapies but identified the need for further research in this area.

To determine the effects of a supervised group exercise intervention on aerobic capacity, anxiety, depression, and quality of life in patients with advanced lung cancer

The intervention consisted of physical and relaxation training in groups of 10–12 patients provided twice weekly for six weeks. Exercises included cycling and strength training supervised by a physiotherapist. Study assessments were done at baseline and at six weeks.

• N = 71
• MEAN AGE = 66 years (range = 31–88 years)
• MALES: 42.8%, FEMALES: 57.2%
• KEY DISEASE CHARACTERISTICS: All patients had advanced inoperable lung cancer and were receiving chemotherapy. Most were receiving carboplatin-based treatment.
• OTHER KEY SAMPLE CHARACTERISTICS: The majority of participants were employed full- or part-time

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

• PHASE OF CARE: Active antitumor treatment

Quasi-experimental

• Peak VO₂ for aerobic capacity
• 6-Minute Walk Test (6MWT)
• FEV₁
• Functional Assessment of Cancer Therapy (FACT) general and L for quality of life
• Hospital Anxiety and Depression Scale (HADS)

There were significant reductions in anxiety scores (ES 0.21, -0.9 change, p = 0.007). There was no effect on depression scores. Aerobic capacity, functional capacity, and muscle strength improved significantly.

The findings of this study suggest that group exercise sessions may benefit the managing anxiety and increase functional capacity among patients with advanced lung cancer. Changes were statistically significant; however, actual change scores were small. The clinical relevance of these changes is not clear.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: Although significant effects were seen, actual changes scores were small, calling into question the actual clinical relevance of findings. There was a withdrawal rate of about 50%, suggesting that this program may not be practical. Patients self-selected to participate in the program, so the sample was potentially biased. The intervention was provided in a group setting, so it is possible that the change in anxiety was related to participating in a group of individuals with the same problems rather than the exercise itself. An analysis of drop-outs showed that baseline functional capacity was significantly higher among those who remained in the program.

The findings of this study suggest that group exercise sessions can improve function and might reduce anxiety among patients with advanced lung cancer. This type of approach may not be feasible or acceptable for patients with very poor baseline functional capabilities. Additional well-designed research in this area would be helpful, and studies should include attentional control conditions to differentiate the affects of group support versus other aspects of the intervention.

To evaluate, postsurgically, the impact of beauty treatments, in combination with routine cancer care, on body image, psychological distress, and coping in patients with breast cancer

Intervention beauty treatments occurred at the hospital during the first week postsurgery. Intervention treatments included manicures, pedicures, makeup, depilation, hairdressing, and massages. The control group received routine medical care. Data collection occurred at baseline (the day before surgery), at six days postsurgery (Time 1), and at three months postsurgery (Time 2).

• The sample was composed of 100 participants; 50 were in the intervention group and 50 were in the control group.
• In the experimental group, 56.7% of participants were between 40 and 60 years old. In the control group, 62.8% of participants were older than 60.
• All participants were female.
• All patients had undergone mastectomy or tumorectomy.

• Single site
• Inpatient
• France

Active treatment

Randomized prospective controlled trial

• French version of the Hospital Anxiety and Depression Scale (HADS), to measure psychological distress.
• Body-Image Questionnaire (BIQ), to measure satisfaction with body image.
• French version of the Mental Adjustment to Cancer (MAC) Scale, to measure coping style. The instrument consists of five subscales: fighting spirit, helplessness and hopelessness, anxious preoccupation, avoidance, and denial.

Depression scores measured by HADS increased significantly over time in both groups (p < 0.001). Anxiety scores measured by HADS decreased significantly over time in both groups (p < 0.001). Investigators noted no significant intergroup difference or interaction effect for both depression and anxiety. Three months after surgery, the intervention group reported higher body-image scores. Patients' perception of helplessness and hopelessness increased over time in the control group but not in the intervention group (p < 0.05).

Overall, this study did not find that beauty treatment had an effect on psychological distress and coping styles.

• The study had a small sample size, with fewer than 100 participants.
• Investigators did not give enough attention to the control group.
• Investigators did not describe randomization procedures. Whether groups were treated sequentially or concurrently is unclear.
• The report presented no justification for the choice of data-collection time points. Patients might have had beauty treatments on their own.
• Investigators did not evaluate the impact that other cancer treatments (chemotherapy or radiation treatment) or other potentially confounding variables may have had on study outcomes.

Cost-effectiveness needs to be examined, particularly given the fact that the investigation yielded no significant findings.