Berenstein, E.G., & Ortiz, Z. (2005). Megestrol acetate for the treatment of anorexia-cachexia syndrome. Cochrane Database of Systematic Reviews, 2, CD004310.
To evaluate the efficacy and safety of megestrol acetate (MA) in palliating anorexia-cachexia syndrome in patients with cancer, AIDS, or other underlying pathologies
Studies that met the following eligibility criteria were reviewed.
Data extraction was conducted by two independent authors. Methodological quality was assessed using the Oxford scale (Jadad, 1996). Scores for methodological quality were generally high. Studies in which more that 50% of patients were lost to follow-up were excluded from the analysis.
Results for MA versus placebo: In patients with cancer, a statistically significant improvement in appetite was observed in the patients treated with MA. Weight gain also was observed in this group.
Results for MA versus other drugs: MA did not show benefits in terms of appetite improvement in comparison to other drugs. Significant differences in quality of life were not reported.
Results for different dose levels of MA: Using 400–800 mg as a cutoff and comparing high to low doses, significant differences in appetite outcomes could not be appreciated.
MA improves appetite and weight gain in patients with cancer. Due to study heterogeneity, no overall conclusion can be drawn about its impact on quality of life; a more systematic approach was suggested for the measurement of quality of life in the trials. The clinical effects of MA do not appear to be dose-related, and the mechanism by which MA increases weight gain is unknown.
MA cannot be recommended for use in patients with AIDS or anorexia-cachexia related to other pathologies. Edema, included in the adverse event profile of MA, is the only significant difference between the treatment and a placebo.
Berenson, J.R., Yellin, O., Shamasunder, H.K., Chen, C.S., Charu, V., Woliver, T.B., . . . Vescio, R. (2014). A phase 3 trial of armodafinil for the treatment of cancer-related fatigue for patients with multiple myeloma. Supportive Care in Cancer. Advance online publication.
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.
Double-blind, randomized, crossover-controlled trial
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.
Armodafinil, a medication similar to modafinil, was not shown to be effective for the reduction of fatigue, anxiety, or depression.
Benson, A.B., Ajani, J.A., Catalano, R.B., Engelking, C., Kornblau, S.M., Martenson, J.A., . . . Wadler, S. (2004). Recommended guidelines for the treatment of cancer treatment-induced diarrhea. Journal of Clinical Oncology, 22, 2918–2926.
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.
Bensadoun, R.J., Schubert, M.M., Lalla, R.V., & Keefe, D. (2006). Amifostine in the management of radiation-induced and chemo-induced mucositis. Supportive Care in Cancer, 14, 566–572.
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.
Bennett, M.I., Johnson, M.I., Brown, S.R., Radford, H., Brown, J.M., & Searle, R.D. (2010). Feasibility study of transcutaneous electrical nerve stimulation (TENS) for cancer bone pain. Journal of Pain, 11, 351–359.
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.
A randomized, controlled, double-blind, crossover design was used.
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.
Bennett, M.I., Bagnall, A.M., & Jose Closs, S. (2009). How effective are patient-based educational interventions in the management of cancer pain? Systematic review and meta-analysis. Pain, 143(3), 192–199.
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
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.
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.
Bennett, M.I., Laird, B., van Litsenburg, C., & Nimour, M. (2013). Pregabalin for the management of neuropathic pain in adults with cancer: A systematic review of the literature. Pain Medicine, 14, 1681–1688.
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.
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.
Bennett, M.I. (2011). Effectiveness of antiepileptic or antidepressant drugs when added to opioids for cancer pain: Systematic review. Palliative Medicine, 25, 553–559.
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.
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.
Bennett, S., Pigott, A., Beller, E.M., Haines, T., Meredith, P., & Delaney, C. (2016). Educational interventions for the management of cancer-related fatigue in adults. Cochrane Database of Systematic Reviews, 11, CD008144.
STUDY PURPOSE: To evaluate the effectiveness of educational interventions for managing fatigue in adults with cancer
TYPE OF STUDY: Meta-analysis and systematic review
PHASE OF CARE: Multiple phases of care
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.
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.
Bennett-Guerrero, E., Pappas, T.N., Koltun, W.A., Fleshman, J.W., Lin, M., Garg, J., . . . SWIPE 2 Trial Group. (2010). Gentamicin-collagen sponge for infection prophylaxis in colorectal surgery. New England Journal of Medicine, 363, 1038–1049.
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.
Multiple sites
Multiple phases of care
Phase III blinded randomized, controlled trial
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.