The purpose of the study was to determine what role glutamine plays in preventing peripheral neuropathy.

The author searched PubMed from 1990 to May 2008 with the key words glutamine, chemotherapy, peripheral neuropathy, neurotoxicity, safety, paclitaxel, platinum compounds, and vinca alkloids. To be included, studies had to evaluate the role of oral glutamine in preventing and treating chemotherapy-induced peripheral neuropathy (CIPN). Studies were excluded if they used glutamine in the reduction of other radiation or chemotherapy-induced related toxicities such as mucositis, cardiotoxicity, diarrhea, and cachexia.

Three clinical trials were reviewed for sample, inclusion/exclusion criteria, study design, and results given. No type of measurement was used to review the study quality. Of note, the article did not state if other studies were found in the literature review.

• The total sample of the three studies combined was 195 patients.
• Patients in study 1 had stage IV breast cancer, no mention of stage was made in study 2, and patients in study 3 had metastatic colon cancer.
• In study 1, 33 patients on glutamine and 30 not on glutamine received a first cycle of high-dose paclitaxel.
• In study 2, 29 patients were placed in a control group and 17 in a glutamine group receiving first cycle of high-dose paclitaxel.
• In study 3, 42 patients received glutamine and 44 did not, receiving one cycle (two doses) of oxaliplatin.

Study 1 suggested that glutamine helps to decrease symptoms of peripheral neuropathy.  Study 2 suggested that glutamine can help prevent some symptoms of CIPN. And, finally, study 3 suggested that glutamine may reduce the occurrence of CPIN.

Although each study had a small sample size, glutamine did appear to help reduce symptoms of neuropathy. However, the systematic review concluded that a lack of sufficient evidence existed to recommend oral glutamine for the prevention of CIPN. Glutamine could be beneficial in patients receiving high-dose paclitaxel and oxaliplatin.

• Regarding limitations, none of the studies were placebo-controlled and endpoints were subjective.
• Criteria to evaluate CPIN differed among all three studies and no standard tool or measure was used to document CPIN.
• The long-term effect of glutamine was not studied, and the symptoms may have been reversed after chemotherapy discontinuation.
• The use of only one database likely hindered the research, as did the small number of studies included.

The safety and tolerability of glutamine was not mentioned.

To determine if e amino-caproic acid (EACA) will reduce perioperative blood loss in patients with cancer undergoing orthopedic surgery (intraoperative plus 48 hours)

• N = 69
• OTHER KEY SAMPLE CHARACTERISTICS: Undergoing major orthopedic surgery

• LOCATION: Memorial Sloan-Kettering Cancer Center

• Randomized, double-blind, placebo-controlled trial of IV aprotinin, EACA, or saline placebo

• D-dimer levels, red blood cells (RBCs) transfused, and bleeding, which was defined as hemoglobin, hematocrit, platelet count, prothrombin time, PPT
• Measurements occurred at three times: preoperative, postanesthesia care unit, and postoperative on day two
   

Blood loss and RBC units transfused did not differ. The two treated groups had a significantly lower D-dimer level (P < 0.01).

• Sample size
• Power insufficient, especially with three arms

To evaluate the efficacy of low-level laser therapy (LLLT) to reduce the severity of chemotherapy-related oral mucositis in children

Patients were randomized to receive LLLT or sham control interventions. Therapy began on day 1 of diagnosis of oral mucositis and was continued daily for the next three days. Study assessments were done immediately before beginning laser therapy, on day 4 after completion of laser therapy, and on day 7. Individuals who applied the laser treatment were not involved in mucositis data collection.

• N = 123   
• MEAN AGE = 9.54 years
• MALES: 45.5%, FEMALES: 54.5%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Thirty percent were undergoing hematopoietic cell transplantation (HCT), and the majority were being treated for leukemia or lymphoma.

• SITE: Single site   
• SETTING TYPE: Multiple settings    
• LOCATION: Italy

• PHASE OF CARE: Active antitumor treatment

• Double-blind, sham-controlled, randomized controlled trial

• World Health Organization (WHO) Toxicity Scale 
• Visual analog scale (VAS) faces scale for pain severity
• Analgesics used

Progressive decline in mucositis severity occurred in both groups, and no significant difference in grading existed between groups. Pain scores were lower in those treated with laser therapy (p < 0.05), and those getting LLLT required less analgesia.

The findings suggested that LLLT may help the management of pain from oral mucositis among children receiving chemotherapy.

• Unintended interventions or applicable interventions not described that would influence results
• Measurement/methods not well described
• No subgroup analysis was conducted according to the type of analgesia consumed—some were getting morphine and some were getting Tylenol. No subgroup analysis according to disease type or chemotherapeutic agents was received. No information was provided on chemotherapy used.

The findings did not show the efficacy of LLLT among children to reduce the severity of oral mucositis. Further well-designed research is needed to determine if a role exists for LLLT in children receiving chemotherapy.

To determine the feasibility of using electroencephalography (EEG) biofeedback (neurofeedback) and identify its potential effects on cognitive impairment, sleep quality, fatigue, and psychological symptoms.

Neurofeedback was provided using an EEG system that detects and alerts the brain of phase changes to increase brain flexibility and resilience. Single EEG sensors, placed at the left C3 and right C4 for each brain hemisphere, analyze EEG activity for identification of phase state changes in the brain. During the session, the patient listened to music while sitting quietly; brief interruptions of the music signal alerted the patient that the software detected phase changes and was providing the brain feedback. No patient response or action was required because it is believed that the brain uses the feedback for its own self-organization without conscious action. Patients had twice weekly sessions for 10 weeks. Assessments were performed prior to beginning the sessions and during the fourth, seventh, and tenth week of sessions.

• The study included 23 Caucasian women with a median age of 56 years (range 43–70).
• All patients were breast cancer survivors with self-reported cognitive impairment since diagnosis.
• Median time since last chemotherapy was 24 months (range 9–59).
• Of the patients, 26% were taking antidepressants and 39% were taking sleep medication.

The study was conducted at a single outpatient site in Ohio. 

The study has clinical applicability for late effects and survivorship.

The study used a feasibility quasiexperimental design.

• Functional Assessment of Cancer Therapy–Cognitive Function (FACT-C)
• Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F)
• Pittsburgh Sleep Quality Index (PSQI)
• Brief Symptom Inventory (BSI)

Significant symptom presence and dysfunction were reported by this sample at baseline, as compared to normative data. Baseline comparisons to normative sample showed significant differences from the norms in all measures, indicating significant dysfunction. FACT, FACIT, and PSQI scores improved over time, although not at a constant rate over longitudinal time points. At study conclusion, symptom report of dysfunction no longer differed significantly from normative populations on three of four FACT-C subscales, FACIT, and PSQI. The proportion of patients using sleep medications declined from 39% to 17% by study conclusion. No adverse effects of the intervention were identified.

EEG neurofeedback was shown to be feasible and potentially beneficial for improving cognitive function, sleep, and fatigue in breast cancer survivors.

• The study had a small sample size, with less than 30 patients.
• The study had risks of bias due to no control group, no blinding, and no random assignment.
• Unintended interventions or applicable interventions were not described that would influence the results.
• The intervention was expensive, impractical, or required training.
• Findings were not generalizable.
• This intervention requires specialized equipment, training, and setting to provide EEG feedback sessions.
• It was not stated whether patients were receiving any other interventions aimed at these symptoms.
• Cognitive function was measured only with self-report instruments with repeated measures design; thus, self-reported improvements may be because of testing effects.
• No objective cognitive function instruments were used to determine cognitive impairment at time of baseline or improvement in cognitive function over time.
• The sample was a homogenous group of patients, potentially limiting generalizability to other patient groups.

This study reported a potentially promising intervention that may have a positive effect on several symptoms experienced by breast cancer survivors. Additional well-designed clinical trials are needed to assess the efficacy of this approach.

To determine the efficacy and safety of loading dose IV ibandronate in women with metastatic breast cancer and bone metastases

Ibandronate 6 mg per day was administered for 15 minutes on days 1, 2, and 3 of the study, and patients were followed up until day 14 of the study. Pain was assessed by visual analog scale (VAS) and functional performance index on days 1, 7, and 14. Patients were supplied with a pain diary and instructed to record at the same time each evening. Assessments for opioid use were performed using the Morphine Equivalent Daily Dose (MEDD) index.

• N = 13   
• AGE = 18 years or older
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Painful bone metastases

• SITE: Multi-site 
• SETTING TYPE: Outpatient 
• LOCATION: Turkey

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Palliative care

• Phase II, open- label, single-arm study for women with breast cancer and painful bone metastases

• VAS
• Karnofsky Performance Scale Index
• Patient diary
• MEDD
• Lab tests (e.g., red and white cell counts, thrombocyte and neutrophil count, hemoglobin and hematocrit levels, alanine transaminase, aspartate aminotransferase, alkaline phosphatase, gamma-glut, total protein, blood urea nitrogen, Cr, Mg, Ph, Ca, CrCl)

Pain intensity decreased on days 7 and 14 versus day 1 using the VAS. Mean Karnofsky index score increased (80.8 [SD = 13.1] and 80.8 [SD = 13.2] on days 7 and 14 versus 77.7 [SD = 11.7] on day 1; p < 0.005 on both days).

This study demonstrates the short-term safety of an intensive ibandronate dosing schedule as indicated by the good tolerability profile and lack of effect on safety parameters including hematology, blood chemistry, and urine analysis. Intensive ibandronate therapy provides a well-tolerated alternative treatment option to analgesic use for patients requiring rapid relief of moderate to severe metastatic bone pain, particularly patients experiencing breakthrough or opioid-resistant pain.

• Small sample (less than 30)

Ibandronate therapy provides alternative pain relief to patients with breast cancer who have bone metastases and, thus, should improve quality of life with good tolerance and no renal safety concerns.

• Patients were given a tetracaine gel consisting of tetracaine HCL 1.5%, miconazole 2%, ethanol 5%, glycerin 10%, saccharin 0.6%, water 65.3%, starch 15%, tween 20.5%, and flavor 0.5%.
• Patients were instructed to apply the gel on oral mucosa after using mouthwash and 30 minutes before and after meals, approximately six times per day. Gel use was continued until resolution of pain.
• Patients were placed into two groups for statistical analysis: no pain relief (grade 1) or presence of pain relief (grade 2, 3, and 4).

• The studied consisted of 50 patients with head and neck cancer.
• Median age was 61  years with a range of 28–73.
• Patients were receiving external beam radiation therapy (XRT) and had oral mucositis of grade 2 or more. Twenty-two patients (44%) had grade 2 mucositis, and 28 patients (56%) had grade 3 or more mucositis.

The study was conducted between July 2000 and December 2003.

This was a prospective, descriptive study.

• Patients were given a questionnaire to evaluate the effectiveness of the gel using a 1–4 verbal subjective scale with grade 1 = no pain relief and grade 4 = highest grade of pain relief.
• The feasibility and toxicity profile of the tetracaine gel in reducing oral pain were evaluated after a week of gel administration.
• Other indirect parameters included the necessity of drug administration, gastrostomy-tube or parental infusion, weight loss, and interruption of XRT.
• The radiation oncologist used the Radiation Therapy Oncology Group-European Organization for Research and Treatment of Cancer (RTOG-EORTC) scale to evaluate results and determined other supportive therapy.

• A majority of patients (79.2%) reported a reduction in oral cavity pain, and 82.9% reported no side effect. Most patients (71%) had no difficulty in gel application. Some patients reported unpleasant taste (12%) and interference with food taste (39%).
• Planned XRT was less interrupted, although this was difficult to evaluate because of the lack of a control group.

• The study did not include a control group.
• The sample size was small.

To evaluate if discontinuing systematic VRE surveillance and contact isolation of colonized patients affects the incidence of vancomycin-resistant enterococcus (VRE) faecium bacteremia

• N = 2,319   
• AGE = 5–94 years
• MALES: 58/59%, FEMALES: 42/41%
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: Hematologic malignancies: leukemia, lymphoma, BMT
• OTHER KEY SAMPLE CHARACTERISTICS: Underlying malignancies were ALL/AML, CML/MDS/MPD, HL/NHL/CLL, and plasma cell malignancies. No significant differences existed in either group.

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Buffalo, NY

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Pediatrics, elder care, palliative care

Prospective nonrandomized observational study comparing the incidence of VRE faecium bacteremia in colonized patients with hematologic malignancies during the period of active surveillance/contact precautions versus no active surveillance/contact precautions

Comparing study periods, no significant difference existed in incidence of VRE bacteremia, MRSA bacteremia, and C-diff. Antibiotic utilization was not significantly different between study periods. Levofloxacin prophylaxis had no affect on the incidence of VRE bacteremia. Daily chlorhexidine bathing showed no effect on VRE colonization/bacteremia. No significant difference existed in aggregate antibiotic use and incidence of bacteremia ≤ 30 days prior between study periods. Nursing hours/patient day was not significantly different during study periods. No significant difference existed in patient demographics, patients per service, or underlying hematologic malignancies between study groups/periods.

In a single-site institution (with sporadic molecular epidemiology of VRE faecium in patients with hematologic malignancies), the incidence of VRE faecium bacteremia was not significantly different comparing study periods—active surveillance/contact precaution per institutional policy and after discontinuation of policy. Incidence of MRSA bacteremia and C-Diff remained stable.

• Baseline sample/group differences of import
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Unintended interventions or applicable interventions not described that would influence results
• Findings not generalizable
• Single-site study
• Only hematologic malignancies, not generalizable to other cancer types
• Predictive ability limited because of different sequential groups rather than the same group with time matched controls
• Nursing hours/day does not clearly estimate care burden/nurse/patient ratio
• Rates of colonization comparing groups not provided
• Treatment phase or types not collected comparing groups
• Lack of data on compliance with hand hygiene and lack of molecular epidemiologic data on VRE isolates from the second study period
• Role of active surveillance and contact precautions was not examined in clonal outbreaks, so the study may not be applicable to other patient populations with cancer or in outbreaks with different molecular data

A single-site study revealed that VRE bacteremia incidence in hematologic malignancy inpatients was not affected by VRE surveillance/contact precautions. Nursing practice measured as hours/patient day was not an effective measure for influencing nursing-sensitive infection-related outcomes. Larger multisite trials that include nursing-sensitive measures are needed to identify the most effective practices essential to prevent/control VRE bacteremia in high-risk patients.

To provide information about patterns of granulocyte colony-stimulating factors (G-CSF) use in Spanish oncology clinical practice and to compare neutropenia-related outcomes in patients treated daily with G-CSF with patients receiving nondaily G-CSF (pegfilgrastim)

Medical records were reviewed for data collection and analysis of outcomes in patients who received pegfilgrastim compared to those who received daily G-CSF.

• N = 391 patients from 34 participating centers 
• AGE: Older than 18 years
• MALES: 46.4% in daily G-CSF group, 31.8% in pegfilgrastim group  
• KEY DISEASE CHARACTERISTICS: Solid tumors excluding breast
• OTHER KEY SAMPLE CHARACTERISTICS: Had chemotherapy with at least one concomitant G-CSF administration more than two months prior; 79.3% had stage 3 or 4 disease

• SITE: Multi-site
• SETTING TYPE: Outpatient
• LOCATION: Spain

• PHASE OF CARE: Active treatment

• Retrospective, multi-center, observational
  • Each investigator reviewed the most recent charts of five patients treated with daily G-CSF and of another five most recently treated with pegfilgrastim.

• Percentage of patients with grade 3 or 4 neutropenia (absolute neutrophil count [ANC], .0 x 10⁹/L) and incidence of febrile neutropenia (FN), defined as ANC 0.5 x 10⁹/L and temperature 38°C or higher during the same day
• Percentage of patients experiencing dose delays (more than three days during any cycle) and dose reductions (less than 84% of planned dose)
• Percentage of patients with dose intensity was 85% or higher (defined as 85% or more of planned dose for all agents in regimen and three days or less of dose delay)
• FN-related hospitalizations and response to chemotherapy—complete, partial, or nonresponse per physician’s criterion

In the multivariate analysis following adjustment for possible confounding factors, a significantly higher risk (OR 1.73, 95% CI 1.004–2.97) of severe neutropenia was associated with daily G-CF versus pegfIlgrastim. The patient group receiving daily G-CSF had a 73% higher probability of grade 3 or 4 neutropenia. Patients receiving daily G-CSF experienced a greater number of dose reductions (38.4% versus 31/6%, p = 0.116) and delays (54.7% versus 41.7%, p = 0.013). Chemotherapy dose intensity of less than 85% also was greater in the daily G-CSF group (39.4% versus 28.9%,p = 0.030). Response rates also were lower in the daily G-CSF group. Complete responses were 17% for daily G-CSF versus 26.4% for the pegfilgrastim group (p = 0.028) and partial response was 41.2% for daily G-CSF versus 52% for the pegfilgrastim group (p = 0.009), again demonstrating better response in the pegfilgrastim group. The two main adverse reactions reported were bone pain and asthenia, with a higher incidence noted in the daily G-CSF group (6.2% versus 1.7%, p = 0.025). Patients receiving at least five days of daily G-CSF, versus those who received fewer than five days, experienced better outcomes.

G-CSF and pegfilgrastim can reduce the incidence and adverse outcomes of treatment-related neutropenia. If G-CSF is stopped prematurely, the efficacy is compromised. This study demonstrates that G-CSF often is initiated later than recommended following chemotherapy, and patients receive fewer days per cycle than required for optimum efficacy.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement validity/reliability questionable

Daily G-CSF and pegfilgrastim are used prophylactically to reduce grade 3 or 4 neutropenia, incidence of FN, dose delays and reductions, and FN-related hospitalizations, and to increase response to chemotherapy, measured as complete, partial, or nonresponse per physician’s criterion. Suboptimal dosing is more prevalent with daily G-CSF because of starting later than recommended following myelosuppressive chemotherapy and stopping too early.

To test the feasibility of providing a psychoeducational intervention for people with head and neck cancer.

The NuCare coping strategies program used a self-study book and audiocassette designed to enhance personal control and teach emotional and instrumental coping responses. It consisted of training in problem solving, relaxation, coping skills, goal setting, communication, social support, and lifestyle factors. Three participants chose to receive it in a small group format, 33 chose one-on-one sessions with a therapist, and 23 chose a home format with no therapist. The outcomes measured were quality of life (QOL), anxiety, and depression.

• The study was comprised of 66 patients with head and neck cancer; 59 completed the program and 50 gave outcome data.
• No age, gender, race, or ethnicity demographics were provided.

The study was conducted at the head and neck oncology outpatient clinic of the Montreal Jewish General Hospital, Quebec, Canada.

Patients were undergoing the active treatment phase of care and were evaluated at baseline and three-month follow-up.

This was a prospective, nonrandomized, one-group, feasibility study.

The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLC-C30) was used to measure QOL and sleep.

Patients reported improvement in physical and social functioning and global QOL, sleep disturbance, fatigue, and depressive symptoms.

• Patients were able to choose which format was used.
• The pilot study was not designed to test the effectiveness of the intervention.
• Special training of the research nurse was required.
• There was no cost to patients.

Participants were offered the Nucare coping strategies program (teaches people to cope with cancer, based on the McGill Model of Nursing) in one of three formats:  small group; one on one; and one on one with therapy (home version with materials).  There was no control arm.  Data were taken at baseline and two and three months following the intervention outcome.  Participants chose the study arm.

• Fifty-nine participants completed the study, and there were outcomes data for 50.
• Gender, race, and income were not described. 
• Participants had head and neck cancer.

This was a nonrandomized, no control pilot, feasibility study for delivery in which participants wanted the intervention.

European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30)

Fatigue was improved in 17 (38%) patients overall, and improvement was equal in self (home) to that seen with the use of a therapist.

• Only one cancer group was studied.
• There were costs associated with the use of a therapist.