To compare the tolerability and efficacy of two different titrations of paroxetine in a population of patients with cancer who have depression

Patients who were randomized to slow up-titration started paroxetine 2.5 mg/day, increasing the daily dose by 2.5 mg each third day, until 10 mg/day was reached on day 8. On day 9, the dosage was increased to 15 mg/day, and on day 11, patients reached the full dose of 20 mg/day.

Patients who were randomized to standard up-titration started with 10 mg/day of paroxetine and increased the daily dose to 20 mg/day on day 8.

• The sample size was 20.
• The median age of the slow up-titration group was 60 (range = 40–78), and the median age of the standard up-titration group was 64 (range = 43–78).
• The sample was 30% male and 70% female.
• Cancer types included breast (30%), lung (20%), colorectal (20%), hematologic (10%), head and neck (6.7%), gastric (3.3%), dermatologic (3%), and others (6.7%).
• 46.7% had no active disease, 30% had local active disease, and 23.3% had metastatic disease. 
• For inclusion, patients had to have any stage of cancer and a major depressive disorder or adjustment disorder with depressed mood. By DMS criteria, 30% had major depression and 50% had adjustment disorder with depressed mood.

• Single site
• Outpatient setting  
• Turin, Italy
   

• Active treatment
• Late effects and survivorship
   

Open randomized trial  

• Dosage Record and Treatment Emergent Symptom Scale
• Subjective Side Effects From Medication Scales
• Hospital Anxiety and Depression Scale
• Montgomery Asberg Depression Rating Scale (MADRS)
• European Organization for Research and Treatment of Cancer–Quality-of-Life Questionnaire Core 30
• Hamilton Rating Scale for Anxiety (Clinical Global Impression and Patient Global Impression of Improvement)
   

Both treatment groups showed a significant mood improvement. A significantly higher rate of patients in the slow up-titration group2, compared to the standard titration group, showed no side effects after two weeks (p = 0.005). A total of 46.7% of subjects used in the intent-to-treat analysis were considered responders, according to MADRS results. Nine patients (30%) dropped out because of side effects that included gastrointestinal problems, dizziness, confusion, restlessness, and tremors. The majority of side effects appeared within the first two weeks.

Slow paroxetine up-titration is better tolerated and at least as effective as the standard paroxetine up-titration in patients with cancer who have depression. Fewer than half the patients in the final sample were identified as responders to treatment, and a third discontinued the treatment because of the drug's side effects.

• The sample was small, containing fewer than 30 participants.
• No control group was used. 
• The drop-out rate was high. 
• At baseline patients' severity of depressive symptoms at baseline varied.

Slow up-titration is better tolerated and may support patient compliance.

A large proportion of patients had side effects that caused them to discontinue treatment. In the general population, side effects from antidepressants are associated with discontinuation of treatment. In patients with cancer who may already have significant symptom burden, the benefits of antidepressant treatment need to be considered in this context.

Among patients with cancer, it is not yet clear which patients actually benefit from medication to counter depressive symptoms.

To evaluate the acceptability and estimate the effect size of a multidisciplinary quality-of-life intervention for men with biochemical recurrence of prostate cancer

The intervention involved eight multidisciplinary group sessions consisting of education, goal setting, relaxation training, problem solving, social support, physical activity, and mood management.

• The sample was comprised of 57 men diagnosed with prostate cancer with biochemical recurrence.
• Median age of sample was 76 years.
• Men had prostate-specific antigen only recurrence post surgery or radiation without clinical or x-ray evidence of metastases.
• The sample was 89% white, 10% black, and 1% other.
• Thirty-nine percent had graduated college.

• Outpatient clinic
• Florida

Biochemical relapse phase

A randomized controlled trial design was used.

• Functional Assessment of Cancer Therapy–Prostate (47-item measure of prostate-specific quality of life)
• Memorial Anxiety Scale for Prostate Cancer (18 items)
• Perceived Stress Scale–10 (10 items)
• Profile of Mood States–Brief (30 items)

• No difference was reported between groups.
• Intervention effect size was 0.45 at the end of treatment.

The results did not provide strong support for a meaningful effect of the intervention provided here on anxiety or quality of life in patients with biochemical recurrence of prostate cancer. Findings suggest that this type of intervention is acceptable to the patient population, since there was a high rate of attendance.

• No data or statistical analysis were reported to determine between group differences.
• The study had no appropriate attentional control.

Given the lack of durability, the intense, multidisciplinary nature of this intervention may not be the best use of limited resources. Further, such a multidisciplinary intervention may be difficult to replicate in the community setting.

PROCESS OF DEVELOPMENT: An interdisciplinary panel of experts in cancer pain management prepared these guidelines. When unavailable, recommendations were not made or were made on the recommendation of experts in that area.

• Make patient and family caregiver education about pain management a part of the treatment plan, and encourage patient and family caregivers to participate actively in pain management. 
• Collaborate with patients and family caregivers, taking costs and availability of treatment options into account when selecting pain management strategies. (Panel consensus)

• Perform a comprehensive pain assessment of all patients with cancer at each outpatient visit or hospital admission and use each patient’s self-report as the foundation for the assessment. 
• Include in the comprehensive pain assessment a detailed history to determine the presence of persistent and breakthrough pain and its effects on function; a psychosocial assessment; a physical examination; and a diagnostic evaluation of signs and symptoms associated with common cancer pain presentations and syndromes. 

• Develop a systematic approach to cancer pain management and teach patients and family caregivers how to use effective strategies to achieve optimal pain control.
• Begin a bowel regimen to prevent constipation when the patient is started on an opioid analgesic. 
• Administer a long-acting opioid on an around-the-clock basis, along with an immediate-release opioid to be used on an as-needed basis, for breakthrough pain once the patient’s pain intensity and dose are stabilized. 
• Do not use meperidine in the management of chronic cancer pain. 
• Adjust opioid doses for each patient to achieve pain relief with an acceptable level of side effects. 
• Avoid intramuscular administration because it is painful and absorption is unreliable.
• Use optimally titrated doses of opioids and maximal safe and tolerable doses of coanalgesics through other routes of administration before considering spinal analgesics. (Panel consensus)
• Monitor for and prophylactically treat opioid-induced side effects.
• Clarify myths and misconceptions about pain management, and reassure patients and family caregivers that cancer pain can be relieved and that addiction and tolerance are not problems associated with effective cancer pain management.
• Use cognitive and behavioral strategies as part of a multimodal approach to cancer pain management, not as a replacement for analgesic medications.

• Offer patients who decline to have procedural sedation nonpharmacologic alternatives to decrease procedure-related pain. 

• Implement a formal process to evaluate and improve the quality of cancer pain management across all stages of the disease process and across all practice settings. 
• Evaluate the quality of cancer pain management at points of transition in the provision of services (e.g., from the hospital to the home) to ensure that optimal pain management is achieved and maintained. 

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.