Auret, K., Roger Goucke, C., Ilett, K.F., Page-Sharp, M., Boyd, F., & Oh, T.E. (2006). Pharmacokinetics and pharmacodynamics of methadone enantiomers in hospice patients with cancer pain. Therapeutic Drug Monitoring, 28, 359–366.
To elucidate the pharmacology of methadone in palliative care patients with advanced cancer who have switched from morphine to methadone
The study had a small sample size.
Further studies, to determine if methadone is better than morphine for the treatment of neuropathic pain, are warranted.
Auret, K. A., Schug, S. A., Bremner, A. P., & Bulsara, M. (2009). A randomized, double-blind, placebo-controlled trial assessing the impact of dexamphetamine on fatigue in patients with advanced cancer. Journal of Pain and Symptom Management, 37, 613–621.
To test the hypothesis that use of dexamphetamine in fatigued patients with advanced cancer would produce a clinically significant improvement with minimal side effects.
Patients with a prognosis of more than two months and fatigue rated at least 4 out of 10 were randomized to receive either dexamphetamine or lactose placebo. Patients were given a daily dose of 20 mg in two doses daily at 8 am and noon. Patients were contacted daily by telephone if at home to record acceptability and improve compliance. If the dose was not tolerated, it was reduced by 50%. The trial was conducted for eight days, and measurement was repeated every two days.
Single multisite study in a palliatve care service in Australia
The study was a randomized, double-blind, placebo-controlled trial.
A transient improvement was observed in fatigue in the dexamphetamine arm (p = 0.039) only on day 2 of the trial. No other significant differences existed between groups. Age and sex were significant predictors of severity of fatigue; those who were younger (p = 0.03) and male (p = 0.047) had more severe fatigue. Both groups had nonsignificant improvement in quality of life measures on some subscales, indicating a potential overall placebo effect. Medication was associated with an increased pulse rate, suggesting that the dosage given had a physiologic effect.
Although well tolerated, 20 mg of dexamphetamine does not improve fatigue or quality of life in patients with advanced cancer. This study agreed with null effects reported by others. Short-term results seen may indicate a response to initiation of a psychostimulant, and changing the dosage over time may have more effect.
Optimum dosage across studies has not been defined.
Augusto Souza Noronha, V.R., Araujo, G.S., Gomes, R.T., Iwanaga, S.H., Barbosa, M.C., Abdo, E.N., ... Santos, V.R. (2014). Mucoadhesive propolis gel for prevention of radiation-induced oral mucositis. Current Clinical Pharmacology, 9(4), 359–364.
To determine the efficacy of propolis gel on radiation-induced oral mucositis
Patients applied a coffee spoon (10 g) of propolis gel 5.0% three times a day (every 8 hours) beginning 24 hours before radiation began, continuing throughout radiation treatment, and two weeks post-treatment. The propolis gel was created following Brazilian safety guidelines. Propolis gel was applied on the tongue and then spread on the oral mucosa. Patients could use a swab or a finger covered with a latex glove to spread the gel if they had difficulty moving their tongue. Mucositis, food intake, and pain were measured at a weekly follow-up. Exfoliative cytology of buccal mucosa, palate, and tongue was performed to confirm the absence of Candida-related mucositis.
83.33% of patients did not develop oral mucositis; 8.33% developed grade I and 8.33% developed grade II oral mucositis. Patients reported no pain associated with the propolis gel. More than 80% of patients who participated in the study were satisfied with the product and would recommend its use.
Mucoadhesive propolis gel could be a useful topical alternative for prevention of radiation-induced oral mucositis. In this study, no participants developed severe mucositis. Patients found the propolis gel used in this study to be acceptable and did not report pain or discomfort associated with the application of this product.
At this time, evidence is limited for the use of propolis/bee glue in the prevention and treatment of oral mucositis. In this study, patients found the mixture of propolis gel 5.0% to be an acceptable intervention. The majority of patients in this study did not develop severe mucositis; however, the study has many flaws, including a lack of randomization, no control group, and a small sample size. Additionally, the dose of radiation varied among participants. More research is needed to determine the effectiveness of propolis/bee glue on the prevention and treatment or oral mucositis.
Anusree, A., Sanatomb, D.E., & Latha, T. (2015). Effectiveness of acupressure on chemotherapy induced nausea and vomiting and the functional status among cancer patients receiving cisplatin as radiosensitizer chemotherapy in Kasturba Hospital Manipal. International Journal of Nursing Education, 7, 32–36.
To investigate the effectiveness of acupressure in reducing chemotherapy-induced nausea and vomiting (CINV) and to analyze the correlation between CINV and functional status
The study began on the second day of chemotherapy. Patients were assigned to experimental and control groups that matched patients on gender and type of chemotherapy regimen. Acupressure was provided by the researcher by applying firm pressure to selected acupressure points for 3 minutes bilaterally in the morning and evening for three days. Both groups received standard antiemetics. Patients were asked to complete study assessment self-reports daily for CINV. Metoclopramide was given as an antiemetic.
Two-group, prospective, post-test study
Over the three-day period, nausea scores were lower in the experimental group (p = 0.002). There was a weak negative correlation between nausea and functional status (p = 0.03).
Acupressure might be helpful in reducing CINV. Because of reporting and design limitations, this study does not provide strong evidence for the effectiveness of acupressure.
This study provided weak evidence that acupressure may be helpful in the management of CINV.
Aufforth, R., Jain, J., Morreale, J., Baumgarten, R., Falk, J., & Wesen, C. (2012). Paravertebral blocks in breast cancer surgery: Is there a difference in postoperative pain, nausea, and vomiting? Annals of Surgical Oncology, 19(2), 548–552.
To evaluate the effect of paravertebral blocks on the postoperative pain, nausea, and vomiting of patients undergoing breast cancer surgery with or without axillary staging
Chart review
Retrospective chart review
In patients who had undergone breast cancer surgery, PVB had no effect on postoperative pain, nausea, or vomiting.
This study indicated that PVB might decrease postoperative pain in breast cancer surgery patients with immediate breast reconstruction with tissue expanders. PVB may have an important role in decreasing postoperative pain and opioid analgesic usage in patients electing to have immediate breast reconstruction with tissue expanders.
Auerbach, M., Silberstein, P. T., Webb, R. T., Averyanova, S., Ciuleanu, T. E., Shao, J., & Bridges, K. (2010). Darbepoetin alfa 300 or 500 µg once every 3 weeks with or without intravenous iron in patients with chemotherapy-induced anemia. American Journal of Hematology, 85, 655–663.
To evaluate the safety and efficacy of darbepoetin alfa (DA) administration every three weeks at fixed doses with or without intravenous (IV) iron.
The study used 1:1:1:1 randomization to one of four groups, stratified by platinum versus nonplatinum. The primary endpoint was hemoglobin 11 g/dL or greater, with no iron deficiency. The secondary endpoint was incidence of transfusions and change in Functional Assessment of Cancer Therapy-Fatigue (FACT-F) score from baseline to end of study. DA was administered every three weeks, and dosages were reduced according to hemoglobin levels. Weekly, 400 µg of IV iron were given, and dosages were reduced as warranted based on ferritin levels. Patients were assigned to one of four groups with or without iron with DA at either 300 µg or 500 µg.
FACT-F
DA at 300 µg and 500 µg given every three weeks demonstrated similar benefits, and added IV iron improved treatment response. There were larger increases in hemoglobin level, and increase in hemoglobin level occurred earlier. The proportions of patients with clinically significant increases in FACT-F score were 100% for the DA 300 µg group, 64% for the 500 µg DA group, 66% for those not receiving iron, and 100% for those receiving iron. No evidence existed of a statistically significant interaction between DA dose received and IV iron usage.
Fatigue and hemoglobin levels improved in patients with anemia receiving DA with and without iron.
DA cannot be recommended at any dose for cancer-related fatigue.
Attia, A., Rapp, S.R., Case, L.D., D'Agostino, R., Lesser, G., Naughton, M., . . . Shaw, E.G. (2012). Phase II study of Ginkgo biloba in irradiated brain tumor patients: Effect on cognitive function, quality of life, and mood. Journal of Neuro-Oncology, 109, 357–363.
To test the hypothesis that ginkgo biloba may be helpful for radiation-induced cognitive impairment
120 mg ginkgo biloba was given for 24 weeks and then discontinued for 6 weeks as a washout period. Tests were administered at baseline, 12 weeks, 24 weeks, and 30 weeks after the initial evaluation.
Phases of Care: Late effects and survivorship
An open label phase II study design was used.
Trail Making Test (TMT) results improved significantly from baseline to 24 weeks; however, TMT-Part B continued to improve significantly from week 24 to week 30 after ginkgo was stopped. It is unclear if changes seen demonstrate improvement with treatment or learning effect. Scores for immediate and delayed recall on the Rey-Osterreith Figure were better (p < 0.0002), but these were not measured and reported at 30 weeks. There were no other changes in mental function scores. POMS scores improved for overall mood for the first 24 weeks and then began to decline. By 24 and 30 weeks, only 19 patients remained in the study. Most common toxicities reported were cognitive issues and memory problems. Five patients (16%) discontinued treatment because of gastrointestinal symptoms. One patient discontinued treatment because of intracranial bleed in one patient. Another five patients (16%) discontinued treatment because of no perceived benefit.
Findings from the study do not provide clear support for the effectiveness of gingko biloba on cognitive impairment caused by brain irradiation.
Findings do not support effectiveness of gingko biloba to improve cognitive function in patients who have impairment associated with brain radiation.
Attar, A., Lemann, M., Ferguson, A., Halphen, M., Boutron, M.C., Flourie, B., . . . Barthet, M. (1999). Comparison of a low dose polyethylene glycol electrolyte solution with lactulose for treatment of chronic constipation. Gut, 44, 226–230.
In part A, patients were randomized to receive either PEG plus electrolytes (PEG+E) (n = 60) or lactulose (n = 55) for one month. In part B, 65 patients continued on the treatment for another two months. Patients received PEG+E, irrespective of the laxative they received at the start of part A.
PEG 3350 is an osmotic laxative that opposes the colon’s normal drying action on the feces. The increasing fecal bulk stretches the circular muscle fibers in the bowel wall and triggers myogenic peristalsis. PEG+E provides electrolyte depletion and dehydration that can occur with other laxatives.
Lactulose is metabolized to lactic acid by bacteria in the colon. Those bacteria exert a local osmotic effect, drawing water and electrolytes into the colon from the surrounding tissues to bulk feces.
This was a single-blind, randomized, multicenter study.
The efficacy of PEG+E was evaluated by
Part A
Part B
Use of PEG+E instead of lactulose doubled the percentage of patients successfully treated at three months. PEG+E was found to be a superior treatment compared to lactulose to treat idiopathic constipation. The study was well designed.
Parshall, M.B., Schwartzstein, R.M., Adams, L., Banzett, R.B., Manning, H.L., Bourbeau, J., . . . American Thoracic Society Committee on Dyspnea. (2012). An official American Thoracic Society statement: Update on the mechanisms, assessment, and management of dyspnea. American Journal of Respiratory and Critical Care Medicine, 185(4), 435-452.
A multidisciplinary group of international experts determined the overall scope of these guidelines according to group consensus. This was followed by evidence reviews in key topic areas conducted by committee members with relevant expertise, and all group members agreed on final content.
Databases searched were PubMed and CINAHL (1999- 2009).
Search keywords were dyspnea, breathlessness, and respiratory sensation, with additional keywords according to specific sections. Reference lists of the articles were hand-searched.
Included were
The exclusion criteria were not clearly described.
These consensus guidelines from a respected professional organization fill an important void in the literature by describing the pathobiology and measurement instruments for dyspnea. The brief review of treatment options provides information for clinicians to consider for patients with refractory dyspnea.
Ashton, J.C., & Milligan, E.D. (2008). Cannabinoids for the treatment of neuropathic pain: Clinical evidence. Current Opinion in Investigational Drugs, 9, 65–75.
The purpose of the study was to determine if cannabinoids are useful in treating neuropathic pain.
No specific databases were stated. Key words included ajulemic acid, analgesia, cannabidiol, cannabinoid, cannabis, CB1 receptor, CB2 receptor, ∆9-tetrahydrocannabinol, dronabinol, levonantradol, nabilone, neuropathic pain, and Sativex. Studies were included if they directly assessed pain; studies were excluded if they assessed pain indirectly by indices of general effects (i.e., quality of life or improvement in sleep).
The total number of studies initially reviewed was not stated; however, the final sample included 18 clinical studies from 2000–2008, 2 studies from prior to 2000, and 3 major reviews and/or meta-analyses. The method of study evaluation was not reported.
The sample range across studies was not stated, but characteristics included neuropathic pain from a variety of conditions, including cancer-related neuropathy.
Substantial evidence shows that cannabinoids are beneficial in reducing neuropathic pain from a variety of causes, including CIPN. One notable study prior to 2000 included 36 patients with cancer pain. Two of the reviews and meta-analysis also included studies of people with cancer-related pain. The findings from this subset were not discussed.
Cannabinoids can be useful as an adjuvant medication for treatment of neuropathic pain; however, side effects such as somnolence, ataxia, dry mouth, euphoria, and dizziness limit their acceptance and tolerance with patients. The authors concluded that, while cannabinoids are moderately effective for the treatment of neuropathic pain, cannabinoid drugs with less psychoactivity should be developed.
This report was limited by lack of specific information related to the literature search and sample sizes of studies included.
Based on the data presented, use of cannabinoids are likely effective for treating neuropathic pain in patients with cancer; however, their psychoactive side effects may limit their acceptability and tolerability.