To test the hypothesis that increased exposure to morning bright light would result in less fatigue during chemotherapy.

Women were randomly assigned to bright white light or dim red light groups. Light was administered via a light box. Sixty LED lights were used (red LEDs for the dim light groups and lights with a distribution of energy concentrated in the middle and long wavelengths for the bright light group). The light box was placed on a table or countertop at a distance of about 18 inches and was to be used for 30 minutes every morning on awakening. The boxes were modified to include an integrated meter that recorded the duration of light box use each day. Study measures were obtained at baseline, during cycle 1 treatments, the last week of cycle 1, a treatment week of cycle 4, and the last week of cycle 4.

• The study included 39 women, primarily Cacausian, with a mean age of  53.92 years (range 32–70).
• All patients were newly diagnosed with breast cancer who were set to receive four cycles of chemotherapy containing araC.

Patient homes in California

Patients were undergoing the active antitumor treatment phase of care.

The study was a repeated-measures, randomized, controlled trial.

• Wrist actigraphy
• Multidimensional Fatigue Symptom Inventory–Short Form (MFSI-SF)

No significant changes were observed in fatigue scores for women in the bright light group. Those in the dim light group showed an average increase in fatigue of 11.7 points (p = 0.003) to the last week in cycle 1, and a 22.2-point increase (p < 0.001) by the last week of cycle 4. Scores on the emotional fatigue subscale showed improvement in the bright light group compared to baseline over all study time points, with significant differences shown at the end of cycle 1 (p = 0.006). All other subscales showed increased fatigue in both groups over time. No relationship existed between fatigue scores and actigraphy results. Patients adhered to light box use for an average of 48.7% of the days in the study, with no difference in compliance between groups.

Findings suggested that light therapy may be of some benefit to prevent worsening of fatigue during chemotherapy treatment.

• The study had a small sample size, with less than 100 patients.
• The study had a risk of bias due to no blinding.
• Unintended interventions or applicable interventions not described could influence the results.
• Patient withdrawals were 10% or greater.
• No other interventions that could have influenced fatigue were described or mentioned.

Light therapy may be helpful to patients in reducing fatigue during chemotherapy, particularly in the area of emotional fatigue. This is a low-risk intervention that might be useful. Patients could increase light exposure by spending more time outdoors or by using a light box.

The study analyzed the relative effectiveness and safety of azole antifungal prophylaxis with particular attention to the tri-azoles compared to fluconazole/itraconazole.

Patients at the Royal Melbourne Hospital with AML/MDS undergoing remission-induction chemotherapy from December 1998–January 2010 who received one day or more of azole prophylaxis were included.  Prophylaxis consisted of fluconazole 400 mg daily, itraconazole sodium 2.5 mg/kg twice daily, voriconazole 200 mg twice daily or posaconazole 200 mg three times daily with fatty food. These were started 1–2 days prior to chemotherapy and continued until neutrophil recovery (greater than 0.5 cells/L), occurrence of a confirmed or suspected invasive fungal infection, drug-related toxicity/intolerance, or the patient’s condition becoming palliative. Oral administration was preferred, fluconazole or voriconazole could be given via IV when a patient’s gastrointestinal absorption was considered inadequate.

216 patients were evaluated (57 in the fluconazole group, 59 in the itraconazole group, 82 in the voriconazole group, and 68 in the posaconazole group).

The median age per group was: fluconazole, 57 (range = 20–79); itraconazole, 55 (range = 20–79); voriconazole, 51 (range = 17–81); posaconazole, 51 (range = 19–78).

Regarding key disease characteristics, 197 patients had AML and 18 had transformed MDS. Median duration of neutropenia ranged from 13–16 days. 

Patient receiving TPN per group: fluconazole, 38%; itraconazole, 40%; voriconazole, 21%; posaconazole, 31%.

Fluconazole was used from December 1998 to September 2008, itraconazole was used from May 1999 to January 2003, voriconazole was used from November 2002 to August 2008, posaconazole was used from September 2006 to January 2010.
 

• Single site 
• Inpatient 
• Royal Melbourne Hospital

Active antitumor treatment

The study was a retrospective review.

• Receipt of total parenteral nutrition (TPN) was a marker of severe mucositis.
• Invasive fungal infection onset was defined as the first day of suspicious CT abnormality or positive microbiology or pathological test.  
• Breakthrough invasive fungal infections were defined as occurrence of invasive fungal infection in patients during \"-azole\" prophylaxis or within seven days of drug cessation.   
   

The majority of patients (213/216) underwent chemotherapy for remission-induction or re-induction or relapsed disease. The median duration of neutropenia for fluconazole/itraconazole was significantly longer than voriconazole/posaconazole (16 days versus 14 days, p = 0.003). TPN requirement was 39% versus 26% (p = 0.001), and median duration of prophylaxis was 18 days versus 22 days (p < 0.001).   
Breakthrough invasive fungal infection occurred in 27 patients comprising of probable/proven (11) and possible (16). The incidence of breakthrough invasive fungal infection was significantly lower in the voriconazole/posaconazole group (10 of 125; 8%) versus fluconazole/itraconazole (17 of 85; 20%) (p = 0.011). All probable/proven invasive fungal infections were molds, most commonly aspergillosis.  
Sub-therapeutic drug levels were common in itraconazole (42%), voriconazole (38%), and posaconazole (69%).  
 

In this institution, the use of voriconazole/posaconazole coincided with a significant decrease in the incidence of breakthrough invasive fungal infections.

Risk of bias:

• No control group
• No blinding
• No random assignment
• No appropriate attentional control conditions
• Sample characteristics*
• Findings not generalizable*

*Findings generalizable to only hematologic malignancies. The retrospective nature is not as strong in this study and, although some good information was shared, the results are not as useful to change practice.

This study compared different agents used for antifungal prophylaxis. There is always the need for education of patients and staff of the signs on infection while on prophylactic therapy and the education of taking the medication correctly and changing to an alternate therapy if the risk of impaired gastrointestinal function is greater for particular patients (i.e., severe mucositis).

To determine if electro-acupuncture (EA) is an effective adjunct treatment to manage postoperative pain, nausea, vomiting (PONV), and recovery in patients after a supratentorial tumor resection

In group A, acupuncture needles were inserted into the LI4, SJ5, BL63, LR3, ST36, and BG40 points, then EA stimulation was used with frequencies of 2 and 100 Hz alternating every three seconds at a level of maximum tolerance for each patient. The duration of the intervention was from the induction of anesthesia till the surgery ended. In group C, no needle was inserted.

• N = 88  
• AGE = Group A: 40.7 years (SD = 12.1 years), Group C: 39.1 years (SD = 10.9 years)
• MALES: 47%, FEMALES: 53%
• KEY DISEASE CHARACTERISTICS: Patients who received supratentorial tumor resections
• OTHER KEY SAMPLE CHARACTERISTICS: Patients received a needling test to exclude those who were resistant to acupuncture. Patients who developed a postoperative hematoma or infection were excluded. In addition, patients were excluded if they were obese, pregnant, taking any medications, or had cardiovascular or respiratory diseases.

• SITE: Single site    
• SETTING TYPE: Inpatient    
• LOCATION: Operation room

• PHASE OF CARE: Multiple phases of care

• Double-blinded, randomized, controlled trial

• Postoperative pain on a 0–10 scale
• Incidence of PONV
• Dizziness and feelings of fullness in the head
• Appetite

After six hours of surgery, the Visual Analog Scale scores, the mean total bolus administration, and the effective number of PCIA bolus administrations in the EA group was statistically significantly lower than the control group. During the 6–48 hours, there were no differences in the mean total bolus administration, the effective number of bolus administrations, and the total fentanyl dose between the two groups. There were no differences in PONV between the two groups. Patients in the EA group experienced a lower incidence and degree of dizziness and feelings of fullness in the head compared to patients in the control group. Patients in the EA group could eat more on a liquid diet than patients in the control group 24 hours postoperatively.

EA can reduce postoperative pain, decrease the number of effective PCIA bolus administrations, improve appetite, and decrease dizziness and feelings of fullness in the head for patients who received supratentorial tumor resections.

• Small sample (< 100)
• Measurement/methods not well described
• Measurement validity/reliability questionable

These study findings show that EA may be used as an adjunct treatment to reduce postoperative pain, decrease the number of effective PCIA bolus administrations, improve appetite, and decrease dizziness and feelings of fullness in the head for patients receiving supratentorial tumor resections.

To investigate the analgesic efficacy of venlafaxine and gabapentin on acute and chronic pain after breast cancer surgery

Patients were randomized prior to surgery to one of three groups. The venlafaxine group received 37.5 mg of extended release venlafaxine once daily and a second placebo capsule at bedtime. The gabapentin group received 300 mg of gabapentin daily and another placebo capsule at bedtime, and the placebo group received placebo capsules daily and at bedtime. Medications were started the evening before surgery and continued for the first 10 postoperative days. Anesthesia was standardized. When patients complained of pain in recovery they were given a titrated dose of morphine until the VAS pain score was 30 or less. For the first 24 hours postoperatively, IV morphine at 20–50 mcg/kg was given to maintain Visual Analog Scale (VAS) at or below 30. For the remaining time to postoperative day 10, all patients were given acetaminophen and codeine every six hours and as necessary. Pain scores were recorded at rest and with movement at four, 12, and 24 hours on the first postoperative day, then daily for 10 days, then six months later.

• N = 150 
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All had breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Patients had either radical or partial mastectomies with axillary dissections.

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

• PHASE OF CARE: Multiple phases of care

Double-blinded, randomized, placebo-controlled trial

• Visual Analog Scale (VAS) for pain
• Morphine consumption

Compared to the control group, VAS scores from the second to the tenth day postoperatively were significantly lower in the gabapentin group (p < 0.0003). Compared to controls, VAS scores for pain with movement were significantly reduced for those receiving venlafaxine during days 8–10 (p < 0.0002). Total morphine consumption in the first 24 hours was lower in the gabapentin group compared to both other groups (p < 0.0001). Significantly more patients in the control and gabapentin groups were using opioids for pain at six months (p < 0.05). There were differences among groups in the type of pain reported at six months, but there were no consistent or significant differences in overall pain results. Patients who received venlafaxine had lower prevalence of burning and stabbing or pricking pain. There were no differences between groups in terms of side effects.

The perioperative administration of gabapentin was associated with decreased pain during the acute phase after breast cancer surgery, but it did not appear to have an effect on the incidence of chronic pain after six months postoperatively. The administration of perioperative venlafaxine may have had a beneficial effect on chronic postmastectomy pain syndrome.

• Other limitations/explanation: There was no description or analysis of differences by type of surgery, and it could be expected that individuals who had more extensive procedures could have had more acute and chronic pain.

The findings of this study showed that perioperative gabapentin was associated with reduced pain in the acute postoperative period among women with breast cancer. The use of venlafaxine may have some benefit for long-term neuropathic pain postmastectomy, but these findings were not definitive. This adds to a growing body of evidence regarding the efficacy of gabapentin in reducing acute surgical pain and points to the need for additional research regarding interventions and the potential role of venlafaxine for postmastectomy pain syndrome.

 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.