To determine if 0.65 g/kg enteral glutamine daily for 7 days is effective in reducing the incidence and severity of mucositis in pediatric oncology patients when given with chemotherapy

Patients received one course of chemotherapy with glutamine and an identical course without. Alternate patients were given glutamine with course 1 or with course 2.

• The study was comprised of 76 patients, aged 1–21 years.
• The sample was 56% male and 44% female.
• Cancer diagnoses were acute myelogenous leukemia (AML), B-cell non-Hodgkin lymphoma (NHL), Ewing’s sarcoma/primitive neuroectodermal tumor (PNET), rhabdomyosarcoma, osteosarcoma, and other.

The study was conducted at a single site at Yorkshire Regional Centre for Pediatric Oncology and Hematology in the United Kingdom.

Patients were undergoing the active treatment phase of care.

This was a randomized study using the patients as their own controls.

• Patient/parent diaries were used from day 1-21 using Common Toxicity Criteria for nausea, vomiting, diarrhea, oral mucositis, and abdominal pain.   
• Plasma ammonia and glutamine levels were recorded.
• Clinical measurements of weight, height, percentage weight/height, mid-upper arm circumference, total parenteral nutrition (TPN) use, enteral feeding, and other complicatios that could affect eating tolerance during enteral feeding.

No difference was found between the five symptoms or for the total number of children with each symptom.

Oral glutamine did not improve the nutritional status of patients in the study. Even though subjective toxicity scores showed more problems if glutamine was not used, because of the small sample size, the difference was not significant. In addition, 62% took glutamine via enteral feeding tube, therefore eliminating the local effect on the oral mucosa.

• The sample size was small with fewer than 100 patients.
• The study lacked a placebo.
• A number of patients were unable to complete the study.
• Randomizing all potential patients was not possible because of the need to urgently start treatment for some patients.

Further study into what factors resulted in the decreased use of TPN could be of benefit. Further studies are needed to investigate the use of oral glutamine using larger and more diverse populations.

TOTAL REFERENCES RETRIEVED: 470

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Several authors were involved in the review. The initial search was completed by one author; subsequently, two authors performed a secondary screening of identified studies. Lastly, two authors, using the Cochrane “risk of bias” tool, evaluated the remaining studies. Meta-analysis was not done given the heterogeneity of the data.

• FINAL NUMBER STUDIES INCLUDED = 3
• TOTAL PATIENTS INCLUDED IN REVIEW = 86
• KEY SAMPLE CHARACTERISTICS: Sample sizes ranged from 12 to 56 patients of all ages published in the years 1983–1995. Patients included those with APL, acute leukemia, and de novo AML. Two studies compared TXA and placebo; one compared EACA and placebo.

PHASE OF CARE: Transition phase after active treatment
 
APPLICATIONS: Pediatrics, elder care

The authors determined the evidence for efficacy (prevention of bleeding) and safety (lack of thrombosis) to be low-grade. Three studies demonstrated a reduced risk of bleeding, a reduction in platelet transfusion, and a lack of development of thromboembolism.

The findings suggest that antifibrinolytics may reduce bleeding and the need for platelet transfusions. There was no evidence for an increased risk of blood clots secondary to antifibrinolytics. Whether the antifibrinolytics reduced the need for other types of transfusions is unclear. The findings support the need for larger trials.

The small sample size was deemed to be below the optimal information size, and thus is a major limitation.

Nurses are involved in the care of patients with hematologic malignancies at risk of bleeding. It is imperative that nurses become knowledgeable regarding the use of agents that may mitigate this risk.

To explore the efficacy of pegfilgrastim to accelerate neutrophil engraftment following stem cell autotransplant.

Patients were given pegfilgrastim 6 mg subcutaneously the day after autologous peripheral stem cell transplant (ASCT). Controls, who were matched for age, gender, disease, high-dose chemotherapy regimen, peripheral blood stem cell dose, and number of prior therapy lines, received filgrastim beginning five to seven days (median = 7) posttransplant. Filgrastim therapy continued daily for 4 to 10 (median = 6.5) doses.

• A total of 80 patients (62.2% male, 38.8% female) who received intervention (pegfilgrastim; N = 40) and matched controls (filgrastim; N = 40) were included.   
• Mean age was 52.8 years (range 21.3–70.6).
• Half of the patients in each group had multiple myeloma (n = 20) and half had lymphoma (n = 20). The lymphoma group was subdivided into Hodgkin lymphoma (pegfilgrastim group [n = 8], filgrastim group [n = 7]) and non-Hodgkin lymphoma (pegfilgrastim group [n = 12], filgrastim group [n = 13]).

• Multi-site  
• Inpatient   
• Switzerland

Patients were undergoing the active treatment phase of care.

This study was a matched control clinical trial.

Time to neutrophil engraftment was defined as the time to the first of three consecutive days of an absolute neutrophil count (ANC) greater than or equal to 0.5x10⁹/L. No specific measurement tools were used other than checking laboratory values.

The pegfilgrastim group had a significantly shorter median time to neutrophil engraftment than the filgrastim group (9.5 versus 11 days, respectively; p < 0.0001), median duration of neutropenia (6 versus 7 days, respectively; p = 0.0001), median duration of intravenous antibiotic therapy (4 versus 6.5 days, respectively; p = 0.0007), and median hospitalization duration (13 versus 14 days, respectively; p=0.0184). The pegfilgrastim and filgrastim groups had a similar median time to platelet engraftment (11.5 versus 11 days, respectively; p=0.42) and median duration of fever (3 versus 3 days, respectively; p=0.35). The two groups required an equal number of red blood cell and platelet transfusions.

Treatment with pegfilgrastim started the day after ASCT results in earlier neutrophil engraftment and reduced neutropenia compared to patients who received filgrastim beginning five to seven days posttransplant. These differences were more pronounced in patients with multiple myeloma than in those with lymphoma, suggesting that interventions may need to be adjusted based on diagnosis.

• Toxicity outcomes were not compared between the pegfilgrastim- and filgrastim-treated groups.
• Small sample (<100)
• Pegfilgrastim was provided free of charge by the manufacturer. There was no cost difference analysis between the pegfilgrastim- and filgrastim-treated populations. 
• No blinding, with associated risk of bias
   

Infection is a potentially life-threatening risk of ASCT. The longer the period of time between chemotherapy-induced pancytopenia and neutrophil engraftment, the greater the risk.  Findings suggest that pegfilgrastim may be more effective with a single injection rather than multi-day injections with filgrastim.

Fourteen allogeneic patients with 15 episodes of diffuse alveolar hemorrhage (DAH) were treated with Solu-Medrol^®; eight of these patients also received aminocaproic acid 1,000 mg IV every six hours.
 

• MEDIAN AGE = 41 years
• OTHER KEY SAMPLE CHARACTERISTICS: Patients who have undergone allogeneic hematopoietic stem cell transplantation; time to DAH from transplant was 40.5 days (range: 11–177 days); failure to improve was the most common reason for adding aminocaproic acid.
   

• Retrospective study

• 100-day mortality
• Median transplant survival
   

Overall 100-day survival was 60%, and the median transplantation survival was 99 days. Patients treated with aminocaproic acid improved to a 100-day mortality of 44% and 167-day median transplant survival, compared to those not treated with aminocaproic acid with an 83% 100-day mortality and 96.5-day median transplant survival.

• Respiratory failure cause of death in 89%
• Median coagulation parameters were near normal; range with no difference in the two groups
• Small sample size
• Retrospective in nature
   

To determine the effect of postoperative intravenous sufentanil for patient-controlled analgesia (PCA) use combined with music therapy on pain and hemodynamics in patients with lung cancer after surgery

Before operation, a music therapist guided patient to hypnosis with music-assisted progressive muscle relation. During the operation, the music intervention was suspended. At three, seven, 15, and 19 hours after the operation, the music intervention was implemented in one-hour sessions in the intensive care unit.

• N = 60  
• AVERAGE AGE = 53.8 years (SD = 11.2 years) control; 53.5 years (SD = 10.7 years) music
• MALES: 58%, FEMALES: 42%
• KEY DISEASE CHARACTERISTICS: Patients with stages 1 and 2 lung cancer receiving resection
• OTHER KEY SAMPLE CHARACTERISTICS: Exclusion criteria included opioid allergies, blood coagulation dysfunction, asthma, peptic ulcers, liver and kidney disease, hearing impairments, alcohol or drug abuse, mental illness or memory dysfunction, inability to operate PCA, and professional music background.

• SITE: Single site    
• SETTING TYPE: Inpatient    
• LOCATION: Intensive care units

• PHASE OF CARE: Multiple phases of care

Randomized, controlled, single-blinded trial

• Self-Rating Anxiety Scale (SAS)
• Visual Analog Scale (VAS)
• Hemodynamic measurements included systolic blood pressure, diastolic blood pressure, heart rate, arterial oxygen saturation, and respiratory rate.
• Sufentanil consumption and adverse reactions

Participants in the music therapy group had significantly lower VAS scores, blood pressure, heart rate, SAS scores, postoperative analgesic use, and sufentanil doses within 24 hours after surgery when compared to the control group.

Intravenous sufentanil PCA combined with music therapy improved PCA use after lung cancer surgery. Lower doses of sufentanil and less frequent PCA use were reported. In addition, combined therapy reduced blood pressure and heart rate.

• Small sample (< 100)
• Risk of bias (no blinding)
• Measurement validity/reliability questionable

This study suggested that combined music and sufentanil therapy can effectively improve PCA effects and reduce the dose of sufentanil needed while decreasing the blood pressure and heart rate in patients who received lung cancer resections.

The purpose of this study was to assess the efficacy of fluconazole compared to itraconazole in neutropenic patients with hematologic malignancies.

MEDLINE, EMBASE, the Cochrane-controlled trials register, and the Cochrane Library and Science Citation Index were searched.

Key words included itraconazole, fluconazole, hematologic malignancies, meta-analysis.

Only studies published as an abstract or journal article after 2009 were included. Studies not published as an abstract or in a journal were excluded, as were any studies prior to 2009.

6,574 total reference were retreived. 

Two independent reviewers extracted data and entered that data into a freeware program (Review Manager 5.0). Differences expressed as the risk ratio with 95% confidence interval (CI); heterogeneity was checked by using a Q-test; random effects model was used prior to pooling of data; sensitivity analysis to assess if modification of inclusion criteria affected final result; publication bias was assessed by funnel plots.
 

• After exclusion, 9 studies remained in the total sample. 
• Total amount of subjects was 2,254.
• Size of the sample ranged across studies from 59–581.
• Fluconazole dosing ranged from 100 mg PO daily to 400 mg daily; itraconazole dosing ranged from 2.5 mg/kg every 12 hours to 400 mg per day; no other sample characteristics were given (i.e., age, gender, etc.).

Active treatment

Results suggested that prophylaxis with itraconazole is more effective than prophylaxis with fluconazole in prevention of fungal infections and invasive fungal infections (RR = 1.33, 95% CI [1.02, 1.73], p = 0.03). No differences were noted in overall mortality, fungal-related mortality, or proven fungal infections. Fewer patients on fluconazole were withdrawn from studies due to adverse events (RR = 0.45, 95% CI [0.27, 0.75], p = 0.002).

 As there were no differences in mortality or proven fungal infections, it is unclear what outcome was used that showed a difference in efficacy.

• Heterogeneity is a potential problem
• Dosages and duration of both itraconazole and fluconazole were varied throughout.
• No definitions of outcomes used is provided.

While the results support itraconazole, the medication is associated with higher adverse effects.

STUDY PURPOSE: To review randomized, controlled trials on the current evidence on the therapeutic effects of acupoints stimulation for patients with cancer with anxiety and depression

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 11
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,073
• SAMPLE RANGE ACROSS STUDIES: 30–302
• KEY SAMPLE CHARACTERISTICS: Six studies were of breast cancer; one, lung; one, gynecologic; and three involved more than two types of cancer. Eight had a two-arm design, and three had a three-arm design. All assessed anxiety and/or depression.

APPLICATIONS: Palliative care

Overall, the findings really did not support acupoints as a useful approach for managing anxiety and depression. Although it has limited risks, it may be useful in patients who do not tolerate oral medications. Results should be interpreted with caution because of the limitations identified. Still, much needs to be researched in this area. Study heterogeneity and lack of standardization of care and design are some of the major limitations to this meta-analysis. Further studies including controls for environmental as well as study site differences are needed before these results can be interpreted. Generalizability is not possible outside of the current study demographics, which should also be taken into account for future studies.

• Limited number of studies included
• Mostly low quality/high risk of bias studies
• High heterogeneity

Acupoints could be a safe intervention used in clinical practice for patients with cancer who experience anxiety and depression. No serious harm was reported, so it could be used as an alternative to medications when patients do not tolerate. Still, much research needs to be conducted in this area.

To compare the cost-effectiveness of various strategies of myeloid growth factor prophylaxis for reducing the risk of febrile neutropenia (FN) in patients with non-Hodgkin lymphoma in Singapore who are undergoing R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy with curative intent

Seven prophylaxis strategies were evaluated: (a) primary prophylaxis (PP) with biosimilar filgrastim throughout all cycles of chemotherapy, (b) PP with biosimilar filgrastim during the first two cycles of chemotherapy, (c) secondary prophylaxis (SP) with biosimilar filgrastim, (d) PP with pegfilgrastim throughout all cycles of chemotherapy, (e) PP with pegfilgrastim during the first two cycles of chemotherapy, (f) SP with pegfilgrastim, and (g) no prophylaxis (NP). Cost-effectiveness was expressed as the cost per episode of FN avoided over six cycles of chemotherapy.

• N = N/A   
• AGE = N/A
• MALES: N/A, FEMALES: N/A
• CURRENT TREATMENT: Chemotherapy, immunotherapy
• KEY DISEASE CHARACTERISTICS: Patients with non-Hodgkin lymphoma (NHL) treated with R-CHOP

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

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

• Case-controlled study using published data set to estimate the rate of FN
• A mathematical model was used to compare anticipated costs.

A Markov model was constructed with TreeAge Pro 2013 to compare seven prophylaxis strategies for FN. Primary prophylaxis was defined as the routine administration of a granulocyte–colony-stimulating factor (G-CSF) with each cycle of chemotherapy, regardless of whether the patient had previously experienced an episode of FN. Secondary prophylaxis was defined as the initiation of a G-CSF in subsequent cycles of chemotherapy after the patient experienced a FN episode. The model target population was a hypothetical cohort of patients with NHL (mean age = 55 years) undergoing R-CHOP as a curative treatment. The time horizon of this model was 18 weeks, which was the period of six chemotherapy cycles. The Markov model was used with a cycle length of one week (seven days). Data from observational studies were used to determine the anticipated rate of FN.

The costs associated with the strategies were $3,813 (strategy 2), $4,056 (strategy 5), $4,545 (strategy 1), and $5,331 (strategy 4), respectively. The incremental cost-effectiveness ratios were $13,532 for strategy 5 versus strategy 2, $22,565 for strategy 1 versus strategy 5, and $30,452 for strategy 4 versus strategy 1, respectively, per episode of FN avoided. Strategy 2 was the most cost-effective.

The routine use of prophylactic G-CSF in the first two cycles of R-CHOP for NHL was more cost-effective than the routine use of G-CSF for all cycles of chemotherapy, with minimal clinical significance on efficacy. Routine use of prophylactic G-CSF during the first two cycles of R-CHOP for NHL or during all cycles of R-CHOP was more cost-effective than no prophylaxis.

• Risk of bias (no random assignment)
• This study used a mathematical model with data sets to predict the costs associated with G-SCF use.
• The study did not enroll patients to evaluate outcomes.
• The authors assumed that using a biosimilar filgrastim for seven days would have the same outcomes as pegfilgrastim.

Using G-CSF is a cost-effective way to prevent FN in patients undergoing R-CHOP chemotherapy. Cost-effectiveness is further improved when a G-CSF is used during the first two cycles, but this may produce different clinical benefits, requiring further study.

To examine the effects of a multidisciplinary intervention on fatigue

The intervention group received training in individual sessions at week one, three, and six. A physical therapist provided education in deep breathing and designed a program of physical exercises to do at home. A nutritionist assessed needs and educated patients in nutrition during therapy. A nurse met with the patient, providing general psychoeducational intervention. All specialists had sessions with the patient at all study time points.

• N = 60   
• MEAN AGE = 56.1 years
• AGE RANGE: 45–65 years
• MALES: 68.3%, FEMALES: 31.7%
• KEY DISEASE CHARACTERISTICS: Lung cancer, undergoing chemotherapy
• OTHER KEY SAMPLE CHARACTERISTICS: Fatigue, pain, and peripheral neuropathy were the most frequent symptoms at baseline.

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

• PHASE OF CARE: Active antitumor treatment

• RCT

• Piper Fatigue Scale

At the end of the study, the trial group had a lower fatigue score than controls (p = .036).

A multidisciplinary intervention to promote self-care may reduce symptoms of fatigue.

• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Other limitations/explanation: No information about patients' actual practice of exercise and other recommendations is provided. No baseline fatigue levels are provided.

Education provided by a multidisciplinary group may be beneficial and positively impact fatigue during cancer therapy.

The purpose of the study was to evaluate whether oral glutamine reduced the incidence and severity of peripheral neuropathy in patients receiving oxaliplatin.

A total sample size of 86 patients with colorectal cancer were enrolled. Forty-two patients received glutamine and 44 did not. Patients received oxaliplatin 85 mgm/m², 5-FU  bolus 500 mgm/m², and folinic acid 20 mgm/m². Patients received glutamine 15 g twice a day for seven days every two weeks starting on the day of treatment. Patients were assessed at baseline for neurological toxicity and electrophysiological toxicity and again assessed at cycles 2, 4, and 6.

The 86 patients enrolled in the study had adenocarcinoma of the colon or rectum.

The study took place from September 2004 to December 2005.

The study had a non-randomized, pilot design.

Glutamine supplementation significantly reduced the incidence and severity of oxaliplatin-induced neuropathy. After two cycles of treatment, grade 1–2 sensory neuropathy was significantly lower in the intervention group versus the control group. The percentage of grade 3–4 sensory neuropathy was lower in the glutamine group after four cycles of treatment and remained that way for six cycles. In addition, glutamine supplements lowered peripheral nerve hyperexcitability and interference with activities of daily living. Glutamine supplementation also reduces the need for oxaliplatin dose reduction without affecting response to chemotherapy and survival.

• Concerns exist concerning glutamine supplements possibly protecting tumor cells from the cytotoxic effects of chemotherapy.
• The study was a non-placebo controlled, non-blinded study with a relatively small sample size; therefore, causality cannot be inferred.
• There was no between-group difference detected. 

Glutamine is a potential neuroprotective agent that needs to be studied in larger populations in a randomized, placebo-controlled trial.