The purpose of the study was to establish efficacy for the use of fluroquinolones in reducing the occurrence of fever in pediatric patients undergoing chemotherapy.

Patients were randomly assigned to receive 10 mg/kg per day of ciprofloxacine orally or placebo twice daily within five days after beginning chemotherapy. Young children who could not take pills were given a liquid form. Axillary temperatures were to be taken every eight hours. Outpatients were seen weekly for evaluation.

• 95 total patients
• Patients were aged 3 months to 18 years
• Patients had acute lymphoblactic leukemia and lymphoma

A single-site inpatient setting.

• The phase of care was active antitumor treatment
• The application was in pediatrics

The study was a prospective, double-blind, randomized, placebo-controlled trial.

• Bacterial isolation tests for infection sites and rectal swabs.
• Infections classified as microbiologically documented, clinically documented, or fever of unknown origin.

The median duration (IQR) of prophylaxis was longer in the ciprofloxacin group than in the placebo group (18 days [5–30] versus 10 days [3–15], p = 0.031). The number of patients who continued the intervention after discharge from the hospital also was higher in the ciprofloxacin group than in the placebo group (18/45 (40%) versus 10/50). In 71 patients with neutropenia, a lower proportion developed fever in the ciprofloxacin group than in the placebo group (17/34 [50%] versus 27/37 [73%]; absolute difference in risk, -23%; 95% CI [-45%, -0.9%]; p = 0.046). In subgroup analysis of patients with ALL, again the proportion of patients who developed fever was significantly lower in the ciprofloxacin group than in the placebo group (13/24 [54.2%] versus 24/30 [80%],  absolute difference in risk, -25.8%; 95% CI [-50.4%, -1.3%]; p = 0.042).

Ciprofloxacin can prevent fever in neutropenic patients with ALL during the induction phase of chemotherapy with good tolerance and no serious side effects.

The small sample (less than 100) was a limitation.

Ciprofloxacin was associated with lower incidence of fever in pediatric patients with neutropenia, and was not associated with significant side effects. There was no difference among patients who did not develop neutropenia. Patients with previous use of flouroquinolones as treatment may be  at risk of colonization with flouroquinolone-resistant bacteria, so empiric use in the setting of no neutropenia is not necessarily recommended.  Potential adverse effects of flouroquinolone use in children has been identified as a potential concern. This study provides some evidence in this area. Further research of appropriate prophylaxis in pediatric patients with cancer who are at high risk for infection is needed.

Palifermin was administered at 60 mcg/kg per day for three consecutive days before the initiation of conditioning therapy and again after graft infusion.

A group of 30 patients who had been treated with palifermin and undergone allogeneic hematopoietic stem-cell transplantation (HSCT) were retrospectively compared to a control group of 30 consecutive untreated patients receiving myeloablative conditioning.

• Median age of patients was 38 years old, with a range was 18–59 years.
• Patients had the following diagnoses.
  • Acute myelogenous leukemia (AML)/myelodysplastic syndrome (MDS) (n = 40)
  • Acute lymphocytic leukemia (ALL) (n = 14)
  • Chronic myelogenous leukemia (CML) (n = 5)
  • Chronic myelomonocytic (CMML) (n = 1)
• Patients received allogeneic HSCT after CY/TBI or chemotherapy solely.
• No growth factors were given.

The study was conducted from May 2005 to December 2006 in Austria and Germany.

The study was conducted within a compassionate use program.

The World Health Organization (WHO) Oral Toxicity Scale was used.

• Incidence of grade 2–4 WHO oral toxicity was 60% in the palifermin group and 86% in the control group (p = 0.04).
• Grade 3–4 oral toxicity was present in 37% of the palifermin group and 53% of the control group (p = 0.19).
• Mean duration of oral mucositis (OM) was 6 versus 12 days (p = 0.003) in favor of palifermin. 
• Severity of OM was significantly reduced in the study group at 1.73 versus 2.47 (p = 0.03).
• Palifermin was associated with significantly decreased use of opioids. The median cumulative dose  was 150 versus 378 morphine equivalents (p = 0.04). However, the difference in median time of use was not significant at 6 versus 7 (p = NS).
• Total parenteral nutrition (TPN) use was lower in the palifermin group at 26 versus 15 days (p = 0.002). 
• No significant difference was found in incidence and duration of febrile neutropenia, with the palifermin group at 4 days versus 3 days in the control group (p = NS).
• Hematopoietic recovery was not influenced.
• No significant difference was found in graft-versus-host disease (GVHD).

• The authors declared no funding or financial support by company.
• An historical control group was used.
• The sample size was small.
• No discussion of added costs was included.

To synthesize findings from intervention studies for sleep disturbance in patients with cancer and their caregivers.

Databases searched were PubMed, CINAHL, and PsycINFO.

Search keywords were sleep, sleep disturbance, insomnia, intervention, cancer, oncology, and caregivers.

Studies dated through 2010 that evaluated sleep disturbance/sleep quality as the primary or secondary outcome were included.

• The total number of references retrieved was not stated.
• The method of study evaluation was described for the type of intervention, mode of delivery, dose, and duration but not for study quality.
• There were only two studies that affected caregivers.

• The final number of studies included was 49 (47 targeting patients and 2 targeting caregivers). 
• Thirteen studies were included in the meta-analysis (total of 1,202 patients with cancer). 
• The total sample across all studies was 3,205 patients.
• The sample range across studies was 9 to 276 patients (including patients with cancer).
• Patients had various cancer types, phases of treatment, and stages of disease. 
• Women with breast cancer were studied most commonly.

Intervention groupings analyzed via meta-analysis included cognitive-behavioral therapy (CBT), education, exercise, and complementary and alternative therapies. Effect sizes appeared to be slightly over 1.0 for CBT, close to 0 for education, slightly over 1.0 for exercise, and slightly over 0 for complementary and alternative therapies. Specific effect sizes were only shown graphically, and actual data were not presented. No separate analysis of caregiver effects could be determined. Modes of delivery of interventions varied widely across studies.

Findings suggest at least moderate effects of CBT and exercise for improvement in sleep disturbances for patients with cancer. No substantial effects of exercise and education were demonstrated.

The review was limited by the lack of any data regarding heterogeneity in the meta-analysis, variability of interventions, and modes of delivery to enable any firm conclusions.

Insufficient evidence was provided to draw any conclusions regarding intervention effects for caregivers.

To perform an integrative review of four electronic databases to determine the effectiveness of complementary and alternative medical (CAM) interventions, either alone or as an adjunct to pharmacologic therapy, in alleviating procedure-related pain, anxiety, and distress in children and adolescents with cancer

Databases searched were MEDLINE, CINAHL, PsycINFO, and Cochrane Database.

Search keywords were procedure, pain, anxiety, distress, childhood cancer, pediatric oncology, CAM, and complementary therapies.

Studies were included in the review if

• The studies were case reports or reports of a clinical series or reports of clinical trials that included at least one CAM intervention aimed at reducing procedure-related pain, anxiety, or distress
• The studies reported on a CAM intervention in one of the following: bone marrow aspiration or biopsy, lumbar puncture, injection, venipuncture for the purpose of blood sampling or starting an IV, or percutaneous access (excluding surgical procedure) to an implanted vascular device
• The sample included at least some children and adolescents (that is, young people between the ages of 2 and 18 years) with cancer
• The studies were published in English

Excluded from the review were studies that reported on surgical procedures (except percutaneous access to an implanted vascular device) and on the anxiety and distress of a parent.

• Investigators retrieved a total of 195 references.
• Reviewers read each paper and extracted information, including names of authors, publication year, study design, medical procedure performed, CAM modalities studied, description of study sample, level of evidence, and summary of  results.
• Results were analyzed for themes.

• Thirty-two studies—two meta-analyses, 18 experimental studies, 9 quasi-experimental studies, one nonexperimental study, and two case studies—were included in the review.
• The total sample size was 1,760, with a range across studies of 3–514 participants.
• Eleven studies included children with leukemia only; 13 included children with various cancer diagnoses other than leukemia; and 8 included children with a range of pediatric illnesses, including cancer.
• Seven studies reported on children younger than 10 years, 3 studies reported on older children (10–17 years), and 22 studies included both age groups.

• Phase of care: diagnostic
• Clinical applications: pediatrics, procedure-related

Results suggest that mind-body intervention may be effective, alone or as an adjunct to pharmacologic interventions, in managing procedure-related pain, anxiety, and distress in pediatric patients with cancer. In this population the three most commonly studied mind-body modalities were distraction, hypnosis, and imagery.

Although multiple studies demonstrated the value of CAM interventions, many of the studies were small and incorporated multiple CAM therapies as a single intervention. These types of interventions may be useful, particularly when used in combination with pharmacologic agents, but further research is needed to identify which interventions were valuable.

To investigate whether the addition of a neutral, supersaturated, calcium phosphate (CP) mouth rinse benefits the severity and duration of acute mucositis in patients with head and neck cancer treated with (chemo)radiation

Patients in group A were instructed to use caphosol mouth rinse twice daily with 15 ml solution for one minute plus standard care. Patients in group B were instructed to use standard care consisting of gargling with 15 ml of “magic mouth wash” (hydrocortisone, lidocaine, nystatin, propylene glycol, sodium carboxymethylcellulose, aqua admixture) up to six times per day, swallowing one time out of two. Two experienced physicians conducted visual inspection of the oral cavity and visualized oropharyns weekly until two to seven weeks after completion or until mucositis grade 1 or 0.

• N = 58
• MALES: 84.4%, FEMALES: 15.5%
• Patients had all histological subtypes of head and neck cancer.
• Patients were receiving curative radiation (intensity-modulated radiation therapy of 60–72 Gy over six to seven weeks), primary or postoperative oral mucosa or part of oral mucosa in radiation field, concurrent chemotherapy consisting of 100mg/m² cisplatin at weeks one and four, and induction chemotherapy with docetaxel, cisplatin, fluorouracil, or epidermal growth factor receptor monoclonal antibody.
• Patients were excluded from the study if they had received prior head and neck cancer radiation therapy.

• Single site
• Outpatient radiotherapy department at the University Hospital of Leuven, Belgium

PHASE OF CARE: Active antitumor treatment

• Single center
• Prospective randomized controlled (no placebo) study

• The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 3 (NCI CTCAE 3.0)
• Oral pain was scored with a visual analog scale.

No significant differences were found in grade, time of onset, or duration of peak mucositis between groups. Fewer patients in the study arm experienced grade 3 or higher mucositis (59% versus 71%). Mean time to development  of mucositis was 28.6 days in the study group versus 28.7 days in the control group (p = .96). Duration of mucositis was 22.7 days in the study group versus 24.6 days in the control group (p = .62). No significant reduction in the need for analgesics was found.

An oral solution of neutral CP mouth rinse does not reduce frequency, duration, or severity of oral mucositis or pain in patients treated with (chemo)radiation for head and neck cancer. No evidence supports its standard use.

• Small sample (< 100)
• Key sample group differences that could influence results
• Other limitations include the heterogeneity of the patient population and treatment sample and no assessment of patient characteristics that could influence mucositis (poor oral health, alteration salivary production, alcohol use, or existing mucosal damage).

Mucosal damage continues to be an important and debilitating side effect that warrants continued research.

• Six studies looking at the incidence of bone pain associated with GCSFs in cancer patients evaluating diagnosis, dosing, and incidence
• Five studies looking at incidence of bone pain associated with GCSFs in healthy people evaluating dose and incidence
• Three studies involving elderly patients with lymphoma who received GCSFs evaluating chemotherapy regimens with or without GCSFs and incidence
• Six studies evaluating the prevention and treatment of bone pain with GCSFs in varying forms of interventions with a maximum of two studies looking at opioids, one with no reported relief of pain

There was no real difference between pegfilgrastim and daily GCSFs in terms of incidence of bone pain, and most patients will benefit from the use of NSAIDs to control pain. The authors suggest that patients who do not respond to NSAIDs should consider second-line treatment with antihistamines. The study cites a series of four patients and one case study in which this was effective.

Only one study was cited that evaluated the efficacy of antihistamines in relieving or decreasing bone pain associated with GCSFs from 2005. Main evidence is case reports only.

More studies are needed to evaluate the efficacy of antihistamines versus NSAIDs or acetaminophen in relieving bone pain.

The purpose of this study was to determine if a misoprostol oral rinse would reduce the severity of mucositis in patients receiving high-dose chemotherapy for autologous stem cell transplant.

This multi-center study employed a randomized, double blind, placebo controlled, parallel-group design. Participants were assigned to the misoprostol arm or placebo arm. Subjects swished and gargled the misoprostol or placebo solution (in 15 ml of water), held it in their mouths for 60 seconds, and then swallowed. Administration began 45 min. to 2 hours before the initiation of the conditioning regimen and then every 8 hours until 24 hours after the conditioning regimen was complete. All subjects also received instructions on standard care and instructed not to use other oral care for 1 hour after the misoprostol or placebo solution. The Oral Mucositis Index was used to grade mucositis every 2 to 3 days.

The study was comprised of 48 patients, 22 in treatment arm and 26 in placebo group, with an age greater than or equal to 18 years.
MALES 30%, FEMALES 70%
KEY DISEASE CHARACTERISTICS: Lymphoma, multiple myeloma, or solid tumor patient undergoing autologous stem cell transplant.
OTHER KEY SAMPLE CHARACTERISTICS: Patients could not have been receiving cisplantin/carboplatin conditioning regimens or total body irradiation.

SITE: Multi-site

SETTING TYPE: Inpatient

LOCATION: Six participating sites in the United States

PHASE OF CARE: Active antitumor treatment
APPLICATIONS: Palliative care

Randomized, double-blind, placebo-controlled, parallel group design

• Modified Oral Mucositis Index
• Clinical examination by calibrated examiners
• Photographs
• Visual Analog Scale
• Pain Affect Faces Scale
• Length of hospital stay
• Days of parental nutrition

No statistically significant differences in Oral Mucositis Index scores. No statistically significant differences in the peak mucositis severity scores. No statistically significant differences in pain ratings, length of hospital stay, or days of total parenteral nutrition. There were no serious adverse events.

There was not a statistically significant benefit to using a misoprostol rinse in deterring the development or the severity of oral mucositis in patients undergoing autologous stem cell transplant. There was also no decrease in the length of stay or the use of total parenteral nutrition.

Small sample (<100)

Findings not generalizable

Other limitations/*explanation: The patient population was limited to only those cancer patients undergoing autologous stem cell transplant.

This study provides no evidence to support using a misoprostol mouth rinse to prevent the development of mucositis, decrease the severity of mucositis, decrease the length of stay, or decrease the use of total parenteral nutrition in patients undergoing a non-TBI based or non-cisplatin/carboplatin-based conditioning regimen for autologous stem cell transplant.

570 articles were included in this literature review. Literature contained prevention and/or treatment methods for mucositis. Interventions for treatment of mucositis were given, recommendations against an intervention were provided, suggestions in favor of an intervention were supplied, and suggestions against an intervention were given.

Recommendations included a combination of teeth brushing, flossing, mouth rinsing, and use of growth factors and cytokines in treatment of mucositis. The use of anti-inflammatory agents was also recommended. Low level laser therapy was recommended in prevention of mucositis with specific types of cancer treatment. Cryotherapy was also recommended for patients receiving chemotherapy. A list of natural and miscellaneous agents was recommended for treatment and prevention of mucositis.

Limitations of this study include clinical situations that were not seen in the literature review or that are rare in clinical settings. These limitations occur because of conflicting evidence or not enough evidence provided.

Nurses should be assessing patients' pain control, nutritional support, ability to eat, and oral hygiene practices, and should be teaching on the use of oral care products that are essential for prevention.

To investigate the effects of cyclooxygenase-2 (COX-2) inhibition on the severity and morbidity or oral mucositis in patients with head and neck cancer undergoing radiation based on the role of inflammatory pathways in oral mucositis pathogenesis

Patients were randomized using a one-to-one ratio in blocks of 10 to receive either celecoxib or a placebo. The celecoxib and placebo capsules were identical. The first four patients took 200 mg of celecoxib twice per day beginning five days prior to the first day of radiation therapy and continuing for three days after the conclusion of radiation therapy. Dosing was modified for all subsequent patients to 200 mg of oral celecoxib once per day only on the days of radiation therapy from the first to the last day of therapy. Subsequent patients assigned to the control arm took the placebo once per day for the same duration. Data were collected two to three times per week for the six to seven weeks during which radiation occurred.

• N = 40  
• AVERAGE AGE = 54.6 years 
• MALES: 32 (80%), FEMALES: 8 (20%)
• KEY DISEASE CHARACTERISTICS: Head and neck cancer

• SITE: Multi-site    
• SETTING TYPE: Multiple settings    
• LOCATION: Hartford Hospital (outpatient setting)

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

Prospective, randomized, double-blinded, placebo-controlled, parallel-arm trial

• Oral Mucositis Assessment Scale (OMAS)
• World Health Organization (WHO) oral mucositis scale
• National Cancer Institute's Common Toxicity Criteria (NCI-CTC) Scale version 2
• Brief Pain Inventory (BPI)
• Performance Status Scale (PSS)
• Advanced opioid converter

There was no difference in oral mucositis severity between the celecoxib and placebo groups (p = .67).

The use of a COX-2 inhibitor during radiation in patients with head and neck cancer did not reduce the severity of clinical oral mucositis, mouth pain, dietary compromise, or use of opioid analgesics. This study’s power calculation seems to be weak. The dropout and missing data rate (usually 20%) should be added to satisfy the original power calculation. This increases the significant risk of type II error. Without a study with a larger sample size, this practice cannot be recommended.

• Small sample (< 100)
• Risk of bias (sample characteristics): This study has a significant discrepancy for gender distribution. The study was predominantly male patients.
• Other limitations/explanation: The researchers note that because most of the subjects were on high doses of opioids, the small analgesic effect of 200 mg celecoxib daily may not have been enough of a dose to appreciate a response. They do mention that the four subjects that were on higher-dose therapy (celecoxib 200 mg BID) did not discern any effect on oral mucositis.

This is not an effective option for treating radiation-induced mucositis.

The study focused on the secondary prevention of febrile neutropenia with G-CSF and antibiotics.

G-CSF (5 mcg/kg subcutaneous) or G-CSF with antibiotics (ciprofloxacin 500 mg by mouth every eight hours and amoxicillin 500 mg by mouth or clavulanate 125 mg by mouth every eight hours) daily starting 48 hours after chemotherapy and continuing until the absolute neutrophil count is greater than 2,000 cells/mm³. Patients were included in the study for one treatment cycle.
 

• The 48 eligible patients were adults who received chemotherapy for solid tumors and had experienced a prior episode of febrile neutropenia.
• Patients were scheduled to continue on the same regimen without dose reduction.
• Most patients were receiving treatment for breast, ovarian, or lung cancer.

Two sites in Europe.

Prospective, randomized pilot trial.

Patients were evaluated with:

• Regular complete blood counts
• Temperature monitoring once daily
• Observation for adverse effects of the prophylactic antibiotics.

In the event of a fever, the antibiotic prophylaxis was discontinued and a complete clinical evaluation for infection was completed.

No episodes of febrile neutropenia occurred in the G-CSF group, and only one incident of febrile neutropenia was reported in the combined group (p = 1). Reported side effects were similar and mild.

G-CSF reduced the risk of febrile neutropenia recurrence. Antibiotics did not provide any additional benefit in terms of prophylaxis.

• Not placebo controlled, not blinded.
• Patients were not stratified, and the groups were not balanced, particularly by disease and the number of prior chemotherapy cycles.
• The study was inadequately powered, since the frequency of the outcome measure was close to none (febrile neutropenia episodes).
• Cost implications were discussed but not in detail.