To draw a comparison between the therapeutic effects of treatment modalities (topical steroid, honey, honey plus coffee) in patients with oral mucositis

Patients were randomized to one of three groups that each received a 600 g syrup solution. The solution in the steroid group (S) contained 20, 8 mg Betamethasone solution ampoules. The solution in the honey plus coffee group (HC) contained 300 g of honey plus 20 g of instant coffee. The solution in the honey group (H) contained 300 g of honey. Every three hours for one week, patients were instructed to sip 10 ml of their solution and swallow it. Data were collected prior to the initiation of the intervention and one week later. Patients were not allowed to use any other anti-inflammatory agents during the study. Patients and providers were blinded to the groups.

• N = 75
• AVERAGE AGE = 55.2 years
• MALES: 48%, FEMALES: 52%
• KEY DISEASE CHARACTERISTICS: None presented
• OTHER KEY SAMPLE CHARACTERISTICS: Participants who presented with oral mucositis after chemotherapy during a period of three years at the hospital site; patients with oral mucositis after chemotherapy between 15 and 80 years old

• SITE: Single-site    
• SETTING TYPE: Inpatient    
• LOCATION: Baqiyatallah University Hospital, Tehran, Iran

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Pediatrics, elder care, palliative care 

Double-blinded, randomized clinical trial

• The World Health Organization (WHO) oral toxicity scale was used to grade oral mucositis.
• A physician-rated questionnaire was created and validated for this study (questions not available).

All three regimens significantly reduced oral mucositis at the end of the intervention week (p < .05).

A steroid solution, honey plus coffee solution, or honey only solution reduced the severity of oral mucositis after one week of treatment.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no appropriate attentional control condition)
• Unintended interventions or applicable interventions not described that would influence results
• Key sample group differences that could influence results
• Findings not generalizable
• Other limitations/explanation: The study did not take into account what chemotherapy regimens the participants received or the point in the treatment regimens at which mucositis developed. The study also did not report which disease characteristics the participants had prior to treatment. The study did discuss in great length how each solution was prepared. There was no control group.

Further investigation is needed on this intervention taking into account participants' diseases and chemotherapy regimens received.

To assess the long-term tolerability, acceptability, and consistency of fentanyl-pectin nasal spray (FPNS) in patients with breakthrough cancer pain

Newly enrolled patients participated in four study phases. Phase 1 was screening. Phase 2 consisted of dose titration based on the approach used in controlled trials: The lowest FPNS dose was uptitrated, one dose per episode of pain, to a maximum of 800 mcg per dose until two consecutive episodes of breakthrough cancer pain were successfully treated without causing adverse events. Phase 3 consisted of 16 weeks of open-label treatment: Patients were provided with a four-week supply of FPNS, either 100 mcg/spray or 400 mcg/spray, based on the findings in the titration phase. Patients self-administered FPNS. If FPNS was ineffective, patients could take their usual analgesia. Investigators initiated weekly calls to patients during the first four weeks. In these calls patients and investigators discussed progress, dose adjustments, and side effects. An investigator considered dose adjustment during the participant’s monthly visit. Consideration was based on information in an e-diary, which each patient submitted, and drug-related adverse events. Phase 4 was the end-of-treatment phase. Those previously enrolled in phase III CP043 (FPNS compared to placebo in the United States, Argentina, and Costa Rica) or CP044 (FPNS compared to immediate-release morphine sulphate in the European Union and India) went through phase 3 and phase 4.

• The sample was composed of 403 patients.
• Mean patient age was 53.8 years.
• Of all patients, 53.1% were male and 46.9% were female.
• Patients had to have a histologically confirmed diagnosis of cancer.  
• To be eligible, participants could have more than one type of breakthrough cancer pain or pain in multiple areas; however, only one location and cancer type were considered the target of the medication.
• Participants could not participate if they had
  • Uncontrolled or rapidly escalating background pain or were medically unstable
  • Breakthrough pain not primarily related to cancer
  • Inability to tolerate fentanyl or other opioids
  • History of alcohol or substance abuse
  • Been treated with monoamine oxidase inhibitors or with investigational drugs within the previous 30 days
  • Any disorder or medication use that would adversely affect the normal function of the nasal mucosa

• Multisite
• Outpatient
• A total of 91 centers in Argentina, Costa Rica, the Czech Republic, France, Germany, the United Kingdom, India, Italy, the Netherlands, Poland, Spain, and the United States
   

• Phases of care: multiple
• Clinical applications: late effects and survivorship, end of life, palliative care
   

Multicenter open-label study

• Episode acceptability assessment    
• Breakthrough pain questionnaire
• Electronic diary that recorded patient's overall satisfaction by means of satisfaction scales
• Survey of adverse events recorded in categories (mild, moderate, and severe)
• Objective nasal assessments
• Subjective nasal assessment
   

• Analysis for intent to treat and safety included 403 patients; 356 entered the treatment phase, and 110 completed the full 16 weeks.
• Approximately 25% of the 403 patients experienced treatment-related, treatment-emergent adverse events that were mild to moderate and typical of opioids. Twenty patients stopped treatment because of an adverse event, and nine stopped as a result of an adverse drug reaction.
• Nasal assessments revealed no significant effects.
• Of all treated episodes, 94% required no additional rescue medication. During the study, more than 90% of patients did not have to have their dose increased. Patients were satisfied with overall outcome for 90% of episodes. At 12 weeks, 97% were satisfied with the ease and convenience of FPNS.

Per patient reports, FPNS is generally easy to use and well tolerated for the treatment of breakthrough cancer pain. FPNS doses were relatively stable during this four-month study; typically, multiple dose changes were not required. Spray, as a means of delivery, is a benefit, especially to those who have difficulty taking pills. The FPNS had little effect on the nasal passages. The results of this study appear generalizable, and administration of fentanyl by means of a nasal spray appears to be acceptable in many institutions across the world. All these outcomes indicate that FPNS may be a helpful intervention for the treatment of breakthrough cancer pain.

• The study had a risk of bias due to no appropriate control group.
• Inclusion of individuals with multiple sites and multiple locations of pain and presentation of pain could have affected  outcomes: Focusing on a primary site of pain, for the purpose of a study, is difficult.
• The study was observational and did not include active comparators.
• Selection bias presents a concern, especially considering the acceptability analysis.
   

Education regarding nasal spray administration seems to play a large role in the effectiveness of a spray-delivered intervention. Further research should investigate adverse events, to ensure the well-being of patients.

To investigate constipation and the use of laxatives in patients with chronic cancer pain treated with oral morphine and transdermal fentanyl.

Patients were switched from long-acting morphine to fentanyl patches. Fentanyl doses were calculated with a conversion table based on a 100:1 dose ratio. If the calculated fentanyl dose was higher than 2.4 mg/day = 100 ug/hour (more than 270 mg/day slow-release morphine), more than one patch was used. Patients were treated with oral slow-release morphine for at least six days (morphine phase) until they reported stable pain intensity scores of 40 or less on a visual analog scale (0 = no pain, 100 = worst pain imaginable) for at least two days. Analgesic therapy then was switched from oral morphine to transdermal fentanyl (fentanyl phase). Fentanyl patches were changed regularly after three days. Fentanyl doses were increased when patients reported inadequate pain relief or had to take more than six rescue medications per day. The study was terminated after 30 days of transdermal therapy. Patients who completed the study until day 17 or longer were included in an intraindividual comparison of laxative intake using the Wilcoxon rank test.

• The study reported on a sample of 46 patients (29 males and 17 females).
• Median patient age was 57.5 years (range 31-83).
• Median patient weight was 62.5 kg, and median height was 172 cm.
• Sites of primary cancer included gastrointestinal, head and neck, genitourinary, respiratory, breast, and hematologic.

• Germany, June 1995 to January 1996
• Unclear if inpatient or outpatient; the researcher was based at the University of Cologne.

This was an open, sequential, multi-center study.

• Patient diary recording of intensity on a 0 to 10 visual analog scale three times daily, frequency of breakthrough pain and use of as-needed medications, use of laxatives, and self-assessment of frequency and consistency of defecation.
• European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QOL-C30), with 30 items that assesses nine symptoms and six dimensions of quality of life.
• Blood pressure, heart rate, respiratory rate, and skin reaction at the site of fentanyl application were documented by the treating physician on days 0, 6, 12, 18, 24, and 30.

• Forty-six patients were treated with slow-release morphine (7 were excluded in the morphine phase because stable analgesia could not be achieved), and 39 were switched to transdermal fentanyl.
• Twenty-three patients completed the study. Two patients died from basic disease, 12 were excluded for various reasons, and two did not have enough data available for evaluation.
• The frequency of bowel movements did not change significantly, but the use of laxatives was reduced in 23 and increased in 2 of 28 patients on transdermal fentanyl.
• No significant changes in vital signs were noted.
• Mild-to-moderate skin reaction was noted in five patients.
• The EORTC QOL-C30 symptom scores showed a significant decrease for constipation only.

The use of laxatives was reduced significantly with transdermal fentanyl.

• This was an open study, so prejudices from staff or patients may have biased the results.
• The site of primary tumor was situated in the gastrointestinal tract for about 25% of the patients; in those patients, constipation easily may have been caused by tumor growth.
• It may be questioned whether the conversion from morphine to fentanyl really was equianalgesic. Therefore, less constipation may have been the consequence of lower equianalgesic opioid dosage.
• Results may have been influenced by the high number of patients who dropped out of the study.
• Difference in the degree of constipation experienced by patients between the two analgesics regimens should be confirmed in a randomized, double-blind study that takes into account both constipation and use of laxatives.
• Short-acting morphine was used for breakthrough pain in both arms of the study; as a result, the patients on fentanyl also had morphine on board.
• The laxative used was not standardized; whether this influenced the results is unclear.
• The study was supported by a research grant from a pharmaceutical company.

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.