To study effects of armodafinil on cancer-related fatigue in patients with multiple myeloma

Patients were randomly assigned to study groups in this crossover design study. One group was a treatment-only arm that got armodafinil, and the other was a placebo-first arm that received a placebo followed by armodafinil. Patients received armodafinil 150 mg once daily for 56 days in the treatment-only group. In the other group, patients received a placebo for 28 days and armodafinil on days 29–56. Assessments were done at baseline and at days 15, 28, 43, and 56. Five variations of study assessments were used to address potential memorization effects, and the order in which versions were used was varied.

• SITE: Multi-site    
• SETTING TYPE: Not specified    
• LOCATION: California

• PHASE OF CARE: Active antitumor treatment

Double-blind, randomized, crossover-controlled trial

• Brief Fatigue Inventory (BFI)
• Hospital Anxiety and Depression Scale (HADS)
• Epworth sleepiness scale
• Trail Making Test (TMT) version B
• Symbol Digits Modalities Test (SDMT)
• Digit span test
• Functional Assessment of Chronic Illness Scale–Fatigue (FACIT-F)
• Functional Assessment of Cancer Therapy–General (FACIT-G)

Adverse effects observed during armodafinil treatment were similar between groups. Fatigue as measured by the BFI scale decreased significantly for both groups over time with no difference between groups. Outcomes measured by FACIT scores increased significantly in the placebo-first group by day 28, and FACIT fatigue scores improved significantly in both groups. Anxiety decreased significantly from baseline in both groups. Depression scores only declined significantly in the placebo-first group by day 28. Degree of sleepiness decreased significantly in the placebo group. There were no significant changes in study measures between day 28 and day 56 in which all patients received armodafinil.

Armodafinil was not shown to significantly improve symptoms of fatigue, anxiety, or depression in patients with multiple myeloma.

• Small sample (< 100)
• Other limitations/explanation: 20% drop-out rate prior to day 56; more patients in the treatment-only group dropped out.

Armodafinil, a medication similar to modafinil, was not shown to be effective for the reduction of fatigue, anxiety, or depression.

The type of evidence found was based on review of the literature and clinical expertise.

The panel focused mainly on colorectal cancer and patients receiving chemotherapy with FU and CPT-11 or radiation therapy, so this is not applicable to other populations (i.e., transplant population).

Diarrhea is a challenge for patients receiving chemotherapy and/or radiation therapy for their cancer. Through in-depth gastrointestinal assessments and optimal treatment, nurses are able to minimize the potential for increased toxicities associated with chemotherapy-induced diarrhea.

DATABASES USED: MEDLINE (May 2002–May 2005), selected studies related to amifostine

KEYWORDS: stomatitis, mucous membrane, mucositis (text in titles and abstracts)

INCLUSION CRITERIA: Limited to \"neoplasm\" and English language

FINAL NUMBER STUDIES INCLUDED = 29 trials included, 6 covered in detail; pilot studies and randomized, controlled studies included

SAMPLE RANGE ACROSS STUDIES: Sample sizes range from small to more than 200

KEY SAMPLE CHARACTERISTICS: Patients with head and neck cancer receiving radiation alone; patients with cancers of various origin receiving combination chemoradiation or radiation alone; patients receiving intensity-modulated radiation therapy; and studies examining routes of administration in patients with head and neck cancer, patients with prostate cancer, and patients receiving epirubicin

The study did not provide sufficient evidence for recommendations related to amifostine and prevention or management of oral mucositis. The authors recommended maintaining the original guideline from the Multinational Association of Supportive Care in Cancer—chemoradiation for non-small cell lung cancer for prevention of esophagitis (level of evidence III, grade of recommendation C). Several small studies demonstrated prevention of proctitis in patients with only rectal carcinoma. No effect was shown for other pelvic cancers. Therefore, the authors suggested that the guideline be revised to include the recommendation of amifostine at least 340 mg/m² IV daily prior to radiation (level of evidence III, grade of recommendation B) for rectal carcinoma to prevent proctitis. For patients with hematologic disorders, no significant data could reinforce any recommendations. Possible future uses and routes of amifostine also were discussed.

To determine the feasibility of conducting a larger phase III trial to investigate the effectiveness of TENS for control of cancer-related bone pain

Patients were randomized to receive either active TENS at the first application and placebo TENS at the second application, or vice versa. Researchers responsible for outcome assessments were blinded to patient group. Placebo TENS was delivered using devices that were identical in appearance but delivered no current output. Patients were informed that sometimes they would feel a tingling sensation and sometimes they might not feel this. Patients were instructed not to tell the research observer any sensations they were feeling. Pain intensity measures were obtained at baseline, then repeated after 30 and 60 minutes of TENS application. Patients returned for the second TENS application two to seven days later and experienced an identical procedure. TENS application was given using a single channel device, and placement was based on recommendations for conventional TENS of the International Association for the Study of Pain. Pain was assessed at rest and on a patient-specified movement. Patients continued their current pain medication regimen.

• The study reported on a sample of 24 randomized patients, with 19 analyzed.
• Mean patient age was 72 years, with a range of 40–91 years. 
• The sample was 75% male (18) and 25% female (6). 
• The majority of patients had prostate cancer. Additional types included breast, lung, thyroid, and renal.
• All patients had radiologic evidence of bone metastases, pain rated as at least 3 on a 10-point rating scale, and an expected survival of longer than four weeks.
• Most (87%) were being treated with strong opioids, including morphine, fentanyl, or oxycodone, 79% had previous radiotherapy, and 33% had received biophosphonates.
• The most common sites of painful bone metastases were pelvis, lumbosacral spine, and lower limbs.
• The majority of patients had an Eastern Cooperative Oncology Group performance status of 1 or 2.
• Patients were on stable pain medication regimens.

• Multisite
• Outpatient setting in the United Kingdom

A randomized, controlled, double-blind, crossover design was used.

• Numerical pain rating scale (1–10)
• Verbal rating scale (four categories from no pain to severe pain)
• Short Form McGill Pain Questionnaire (SF-MPQ)
• Patient satisfaction questionnaire designed by authors regarding benefit, ease of use, and impact on pain or rest

The mean pain change in pain intensity score for active TENS was –0.84 compared with placebo TENS of –2.16. The mean change with movement was –2.32 for active TENS compared with placebo change of –2.0. at one hour. The mean pain relief on movement was higher with active TENS. The difference in proportion of patients who reported good or very good pain relief on movement with active TENS by verbal ratings was 36.8% (95% CI 7.5–66.2%). There were no clear patient preferences between active and placebo TENS. Three patients experienced adverse events, increased pain with TENS application, that were deemed likely to be or definitely related to TENS use.

TENS has the potential to provide improved pain relief on movement in patients with bone pain.

The study had a small sample, with less than 30 patients.

The purpose of this study was to determine feasibility and use findings to plan for a phase III study, rather than to determine intervention effect. Findings suggest that TENS may be more effective in pain relief on movement than for pain relief at rest for bone pain. Findings also showed an effect on the measure of pain relief, but not on the measure of pain intensity. This suggests that pain relief measurement may be more useful in clinical trials than just measurement of pain severity at given points in time.

To quantify and compare the benefits of various patient-based educational interventions for cancer pain management; to improve understanding of the relationship between education and improved pain outcomes

• Databases searched were MEDLINE, CINAHL, EMBASE, Applied Social Sciences Index and Abstracts (ASSIA), Allied and Complementary Medicine Database (AMED), and PsycINFO from inception to Nov. 30, 2007, and the Cochrane Library; Database of Abstracts of Reviews of Effects (DARE) and National Institute for Health and Clinical Excellence (NICE) websites; and contents lists of Pain, Journal of Clinical Oncology and Journal of Patient Education and Counseling. In addition, investigators completed manual searches of article reference lists.
• Authors did not include a list of search keywords.
• Studies were included in the review if they
  • Incorporated experimental designs that included a control group.
  • Involved adults with pain from active cancer.
  • Used a patient-based educational intervention on an individual basis.
  • Assessed pain-related outcomes.
• Studies were excluded if they dealt with pain from cancer treatment, such as surgery or chemotherapy.

The search retrieved 61 studies. Authors chose 21 studies for analysis. Twelve studies included pain-outcome data suitable for meta-analysis. Authors used the Cochrane Collaboration recommendations for randomized controlled trials as the basis of study evaluation. Studies were done in six different countries.

• The sample was composed of 3,501 patients. The sample range across studies was 30–1,256.
• Authors did not provide sample characteristics but did state that samples were composed predominantly of females and individuals who were recently diagnosed with a good performance status.

• Analysis of Brief Pain Inventory (BPI) measures only showed significant effects of education on average pain intensity (p = 0.002), maximum pain intensity (p = 0.0004), least pain (p = 0.006), and current pain.
• Effects of patient education on patient knowledge differed according to the scale of measurement. Significant outcomes resulted from the BPI questionnaire and the Pain Experience Scale only.
• Across all studies, authors noted a significant effect on patient knowledge (p = 0.008). Compared to multiple exposures to patient education, single exposure had clearer benefits on knowledge and attitudes and similar effects on maximum pain intensity.
• Effects of knowledge on average pain intensity were inconsistent. Effects on all outcomes were greater when intervention was compared to usual care rather than a placebo group or attentional control.
• Education had no effect on the extent to which pain interfered in daily activities.
• Data showed heterogeneity that authors could not explain, although they noted that in some cases heterogeneity seemed to be associated with measurement type.
• Length of follow-up and the nature of the education varied across studies; therefore, authors could not analyze these factors separately.
• Overall weighted mean difference regarding reduction in pain intensity was 0.76.

Findings demonstrate that patient-based educational interventions for cancer pain improve knowledge and attitudes and can reduce pain intensity. The fact that effects were greater in studies with no attentional control raises the question of the benefits of attention itself. Authors observed that benefits were associated with both single- and multiple-exposure studies. Authors pointed out that the weighted mean difference in pain intensity, with educational interventions, was as large as that reported in another analysis for some types of co-analgesic therapies. This finding supports the clinical relevance of providing patient education.

Most of this research was done early in cancer care and may not be directly applicable to patients in later phases of care. Additional research, with long-term follow-up and other patient groups, is needed.

• FINAL NUMBER STUDIES INCLUDED = 5 
• TOTAL PATIENTS INCLUDED IN REVIEW = 762
• SAMPLE RANGE ACROSS STUDIES: 1– 345 patients
• KEY SAMPLE CHARACTERISTICS: Tumor types and demographic variables not reported

PHASE OF CARE: Multiple phases of care
 
APPLICATIONS: Elder care   

The studies included one case report, two observational studies, one open-label study, and one double-blinded, four-group, randomized, controlled trial comparing pregabalin, gabapentin, amitriptyline, and a placebo. The most common side effects reported with pregabalin were dizziness, somnolence, headache, fatigue, dry mouth, nausea, ataxia, tremor, peripheral edema, weight gain, blurred vision, and constipation.

This review concluded that the current evidence for the efficacy of pregabalin for cancer-related neuropathic pain is too limited to draw any conclusions.

• Only included one randomized, controlled trial, and few studies were included in total

Pregabalin has been suggested as an approach for the management of chronic, neuropathic, cancer-related pain. However, there is very limited evidence to prove its efficacy.

• FINAL NUMBER STUDIES INCLUDED = 8  
• TOTAL PATIENTS INCLUDED IN REVIEW = 370
• SAMPLE RANGE ACROSS STUDIES: 16–121 patients
• KEY SAMPLE CHARACTERISTICS: All had neuropathic cancer pain

PHASE OF CARE: Not specified
 
APPLICATIONS: Palliative care

Six studies examined gabapentin, sodium valproate, or phenytoin, and two studies examined amitriptyline or imipramine. In two randomized, controlled trials, (RCTs) opioid doses were varied according to pain intensity, and in five trials, the opioid doses remained stable. The studies of phenytoin and valproate did not report pain intensities. For gabapentin, two RCTs and two observational studies reported an average benefit of 0.8 points (10-point scale, p = 0.025), but the reports of the percent of patients achieving at least a 30% pain relief were mixed. For amitriptyline, one study reported a benefit of 0.9 points of worst pain (p = 0.035), and one abstract did not report results. For gabapentin, adverse event outcomes were inconsistent; one RCT reported withdrawals caused by the medication, including one death. Respiratory depression was reported in two RCTs. Amitriptyline was associated with increased confusion, dry mouth, and drowsiness. The most common side effects were somnolence and dizziness.

The findings of this analysis suggest that the addition of antiepileptics and antidepressants to opioids for cancer-related neuropathic pain management may result in a small improvement in pain intensity at the risk of more adverse events.

• Relatively small number of studies
• Some study designs associated with a high risk of bias

Adjuvant medications in addition to opioids for cancer-related neuropathic pain may be helpful for some patients; however, there is a need for skillful use and follow-up to evaluate the effect of adverse events. In some patients, these adverse events were severe. At the same time, the small changes in pain intensity reported here raise the question of whether these differences are clinically relevant and sufficient to warrant the risk of adverse events. Pain management needs to be highly individualized.

STUDY PURPOSE: To evaluate the effectiveness of educational interventions for managing fatigue in adults with cancer

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 14 studies  
• TOTAL PATIENTS INCLUDED IN REVIEW = 2,213
• SAMPLE RANGE ACROSS STUDIES: 30–396
• KEY SAMPLE CHARACTERISTICS: Multiple different types of cancer at various phases of care. Most had mild to moderate fatigue at baseline.

PHASE OF CARE: Multiple phases of care

• For general fatigue: SMD = –0.27 (95% confidence interval [CI] [–0.51, –0.04]), showing a positive effect of education. These studies were of low quality.
• For fatigue intensity: SMD = –0.28 (95% CI [–0.51, –0.04]) effect of education. These studies were of moderate quality.
• For fatigue interference: SMD = –0.35 (95% CI [–0.54, –0.16]), showing benefit of education. Studies were of moderate quality.
• For anxiety (three studies): SMD = –1.37 (95% [CI –2.76, –0.18]). Studies were of low quality.
• For depression (four studies of very low quality), no impact on depression was found.
• Insufficient evidence existed to analyze the results according to stage of disease, phase of care, and method of education delivery. Education was delivered individually, face-to-face, in group settings, or with self-use of video or print material. Most interventions included counseling and patient training components.

Educational interventions appear to play some role in reducing overall fatigue, fatigue intensity, and fatigue interference, and might provide some benefit for anxiety. No effect on depression was found in this study, but baseline levels of depression were not generally clinically relevant.

• High heterogeneity

The incorporation of educational interventions as part of care to manage fatigue is reasonable but may not be sufficient to have a clinically meaningful impact.

The purpose of the study was to determine if an implantable gentamicin-collagen sponge prevents surgical infections in patients undergoing colorectal surgery.

Patients undergoing laparoscopic colorectal surgery in one of the 39 sites participating in the trial were randomized into either the sponge group or the control group after the surgical incision was made. If randomized into the experimental group, patients had a sponge (10 x 10 cm) implanted internally along their incision line just prior to the surgeon closing the wound that contained 280 mg of collagen and 130 mg of gentamicin. Both groups received standard of care of antibiotics 60 minutes prior to incision. Individuals who analyzed results were blinded to patient assignment.

• The sample included 602 participants.
• Ages ranged from 45–67 years.
• Males made up 56% of the sample; females made up 44%.
• Patients enrolled underwent surgery for colon or rectal cancer, diverticulitis, or inflammatory bowel disease.

Multiple sites

Multiple phases of care

Phase III blinded randomized, controlled trial

• ASEPSIS score through 60 days postoperatively    
• Serum creatinine peak reported for each patient for up to the first seven days postoperatively depending on discharge date
• Patient self-assessment of pain and wound healing 30 and 60 days postoperatively
• Data was recorded for any enrolled patients with visits to the emergency room, physician office, or readmission to the hospital with wound-related issues
• Serum gentamicin levels were obtained at baseline and up to 48 hours after wound closure
   

Surgical infections occurred more frequently in the sponge group with a rate of 30% as compared to the control group at 20%. Superficial site infections also were higher in the sponge group than the control group. The sponge group also was more likely to visit the emergency department or physician offices with wound-related complications (19% versus 11%).

The gentamicin collagen sponge is not effective in preventing surgical site infections in patient undergoing colorectal surgery.

The study did not determine if the sponge could be used to treat infection but, instead, focused only on infection prevention.

The gentamicin collagen sponge is not only not effective in preventing infection, but based on this study, may increase a patient’s risk for surgical wound infection.

To evaluate a cream containing melatonin in terms of efficacy in reducing acute radiation dermatitis during and immediately after radiation therapy, and to examine patient-reported comfort during the study period

• N = 47, 26 in melatonin group and 21 in placebo group
• AGE = Older than age 18 years
• MEDIAN AGE = 54–55 years
• FEMALES: 100%
• CURRENT TREATMENT: Radiation
• KEY DISEASE CHARACTERISTICS: Stage 0–II breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Status postlumpectomy; no prior radiation to the chest or breast; most patients had fair skin and a body mass index of 24; total radiation dose, 50 Gy, was given as a daily fraction of 2 Gy; patients on 3-D treatment plans; the boost area was not evaluated (additional 10 Gy and 16 Gy); patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; smoker status

• SITE: Single institution   
• SETTING TYPE: Not specified    
• LOCATION: Sheba Medical Center in Tel Aviv, Israel

PHASE OF CARE: Active antitumor treatment

Phase II, prospective, double-blind, randomized

• Radiation Therapy Oncology Group (RTOG) toxicity score
• Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, acute toxicity scoring criteria
• Questionnaires
• Likert-type scale

The researchers reported no significant difference in skin toxicity for both groups for the first four weeks of radiation treatment. The authors reported findings of significance in terms of reduced radiation dermatitis in the melatonin group at week five to seven (p = 0.049). After radiation was complete, the authors reported significant findings at the two-week follow-up visit in terms of reduced dermatitis in the melatonin group (p = 0.03). The researchers found no difference in the melatonin group and placebo group patient questionnaire reports of symptoms during treatment (including pain, burning, itching). Other analysis showed that women in the melatonin group who were older and smoked showed less radiation dermatitis (significance values p = 0.021 and p = 0.007). Four patients in the melatonin group sustained an allergic reaction limited to the treated skin, which required treatment with a topical and/or oral steroid.

Women with early stage breast cancer (stage 0–II) who are status postlumpectomy and undergoing daily radiation treatment for five weeks may experience reduced skin toxicity from the twice daily application of a melatonin containing cream to the treatment area.

• Key sample group differences that could influence results
• Authors identified that their patient sample was comprised of women with a body mass index of 24 and that other patients with higher body mass indexes (i.e., including obese patients) may influence the findings.
• Intervention expensive, impractical, or training needs (was not able to find the cost of the product Praevoskin; unsure if Pharm-Olam, the company that supported/funded this study, is the manufacturer of this product or not; also unclear if other melatonin-containing products would be as useful in reducing the amount of radiation dermatitis)
• Fairly small sample size with patient median age of 54–55 years
• Unclear if results would vary with younger and older patients (e.g., younger than age 45 years or older than age 65 years)

As there is currently no consensus or evidence-based practice to follow for the treatment for radiation dermatitis, this study could be used to identify a treatment option and possibly specific product use in other institutions where radiation is delivered. Although this study was limited to women with breast cancer who had undergone lumpectomy, there could be utility in applying the melatonin cream to patients undergoing radiation therapy for other types of cancers (e.g., head and neck cancer).