Goodwin, J.W., Green, S.J., Moinpour, C.M., Bearden, J.D., III, Giguere, J.K., Jiang, C.S., … Albain, K.S. (2008). Phase III randomized placebo-controlled trial of two doses of megestrol acetate as treatment for menopausal symptoms in women with breast cancer: southwest oncology group study 9626. Journal of Clinical Oncology, 26, 1650–1656.
Southwest Oncology Group Study 9626 evaluated megestrol for management of menopausal symptoms in women with breast cancer. It compared two doses of megestrol acetate versus placebo over six months. Participants were randomized to placebo, megestrol 20 mg, or megestrol 40 mg daily for three months. If success was achieved, treatment continued for three additional months. If not, the patient was unblinded and given megestrol 20 mg daily.
Participants: 288 patients with T 1-3, N0-1 breast cancer following surgery, chemotherapy, and at least four months of tamoxifen, if prescribed, were enrolled. 225 completed the trial.
This was a phase III, randomized, placebo-controlled, double-blind trial.
At the initial evaluation, patients completed a seven-day patient daily log of hot flashes with re-evaluation at three and six months. The primary endpoint was differences in the probability of hot flash reduction in three comparison groups. Instruments included:
At three months, improvement was 14% with placebo, 65% withmegestrol acetate 20 mg, and 48% with megestrol acetate 40 mg. Both doses were superior to placebo (p < .0001). Duration of effectiveness continued at six months. Megestrol 40 mg was not superior to megestrol 20 mg.
The recommended daily dose is 20 mg.
The study was not designed to evaluate long-term toxicities or relapse of symptoms with long-term use. Concern remains regarding the use of progestins in women with a history of breast cancer.
Gonzalez, A.V., Ullmann, A.J., Almyroudis, N.G., & Segal, B.H. (2008). Broad-spectrum antifungal prophylaxis in patients with cancer at high risk for invasive mold infections: point. Journal of the National Comprehensive Cancer Network, 6, 175–182.
To determine if there is sufficient evidence that pre-emptive antifungal treatment is as effective as antifungal prophylaxis with posaconazole. The patient populations addressed included patients with acute myelogenous leukemia or myelodysplastic syndrome with prolonged chemotherapy-induced neutropenia and allogeneic hematopoietic stem cell transplantation (HSCT) recipients with significant graft-versus-host disease.
Prophylactic antifungal therapy is defined as the initiation of an antifungal agent to high-risk patients to prevent a fungal infection. Pre-emptive antifungal therapy is defined as the initiation of antifungal therapy in high-risk patients based on laboratory markers, radiologic monitoring, or both to identify early invasive fungal infections (IFIs) before clinically overt disease develops. The authors based their evaluation on the principle that prophylaxis of fungal infections is important due to the significant morbidity and mortality associated with fungal infections, the incidence in high-risk patients, the safety of available antifungal agents, and the lack of sensitive methods of early detection. A pre-emptive approach is limited by the sensitivity and specificity of available detection methods. The authors reviewed the current literature on posaconazole prophylaxis and pre-emptive antifungal therapy.
No databases used for a search were listed, nor were any inclusion or exclusion criteria mentioned. However, keywords searched were invasive fungal infection, prophylaxis, pre-emptive therapy, and aspergillosis.
One prospective, randomized trial compared posaconazole with fluconazole or itraconazole as a primary antifungal prophylaxis in patients with acute myelogenous leukemia or myelodysplastic syndrome with prolonged chemotherapy-induced neutropenia. Proven or probable IFIs occurred in seven (2%) patients in the posaconazole group and 25 (8%) patients in the fluconazole or itraconazole group (p < 0.001). Significantly fewer patients in the posaconazole group had invasive aspergillosis. Survival was improved in posaconazole recipients (p = 0.04). Serious adverse events possibly related to treatment occurred in 6% of patients in the posaconazole group and in 2% in the fluconazole or itraconazole group (p = 0.01).
One prospective, randomized trial compared primary antifungal prophylaxis with posaconazole versus fluconazole in allogeneic HSCT recipients with significant graft-versus-host disease on immunosuppression. Posaconazole was at least as effective as fluconazole in preventing IFIs during the prespecified period of observation (incidence, 5.3% versus 9%, respectively; p = 0.07) but was superior in preventing invasive aspergillosis and deaths caused by IFIs. If the analysis was restricted to the period in which patients received the study drug, posaconazole was considered superior to fluconazole in preventing IFIs (incidence, 2.4% versus 7.6%; p = 0.004), particularly invasive aspergillosis (incidence, 1% versus 5.9%; p = 0.001). Treatment-related adverse events were similar between the groups. One peer-reviewed publication reported pre-emptive antifungal therapy. The study was a feasibility study in which a total of 136 treatment episodes for patients with neutropenia at high risk for IFI were screened with daily serum galactomannan testing. There was a diagnostic algorithm that included chest computed tomography (CT) scans and bronchoalveolar lavage. Patients who met prespecified criteria for probable or proven invasive fungal infection received pre-emptive therapy with liposomal amphotericin B; neutropenic fever alone did not trigger modification in the antifungal regimen. Although this approach was successful in identifying early invasive aspergillosis and avoiding amphotericin B use in most patients with persistent neutropenic fever of unknown origin, invasive aspergillosis developed in 17 patients and zygomycosis in one patient among 136 chemotherapy treatment episodes. All cases of invasive aspergillosis were identified through positive antigenemia results. Seven (41%) deaths occurred in patients with positive serum galactomannan results; of these, six had autopsy-proven invasive aspergillosis. However, only two patients were considered to have died directly because of invasive aspergillosis.
The authors believe that insufficient evidence exists to recommend a pre-emptive antifungal therapy approach in place of posaconazole prophylaxis in patients with acute myelogenous leukemia or myelodysplastic syndrome with prolonged chemotherapy-induced neutropenia and allogeneic hematopoietic cell transplantation (HCT) recipients with significant graft-versus-host disease.
No conflict of interest was stated.
Posaconazole is recommended as a primary antifungal prophylaxis in patients with acute myelogenous leukemia or myelodysplastic syndrome with prolonged chemotherapy-induced neutropenia and in allogeneic HCT recipients with significant graft-versus-host disease. Pre-emptive treatment is not recommended in these patient populations.
Gonzalez-Barboteo, J., Alentorn, X.G., Manuel, F.A., Candel, V.A., Eito, M.A., Sanchez-Magro, I., . . . Porta-Sales, J. (2014). Effectiveness of opioid rotation in the control of cancer pain: The ROTODOL study. Journal of Opioid Management, 10, 395–403.
To assess the effectiveness of and adverse events associated with opioid rotation for the management of cancer-related pain
All consecutive patients who attended the clinics of participating hospitals were eligible. A single opioid conversion table was used by all participants. If a rotation was used because of pain and toxicity, the baseline dosage was reduced by 25%–50% prior to the change. If no toxicity was present, an equivalent dose was used. Pain was assessed days prior to the implementation of the rotation and one week postimplementation. During the week, changes in opioid dosage were allowed and recorded. Patients were followed for 90 days.
Observational
About 89.5% of patients had one opioid rotation. The most common drugs used for the rotation were morphine, fentanyl, and transdermal buprenorphine. The most common switch was from fentanyl to morphine. The rotation was effective in 75.4% of patients for reducing average pain and in 57.8% for breakthrough pain. Average pain decreased at day 7 (p < 0.001) by four points, breakthrough intensity decreased by four points (p < 0.001), and the number of breakthrough episodes decreased on average from three to one (p < 0.001). Among patients in whom the rotation was effective, there were no significant differences between pre- and postequivalent doses of opioids. In 10 switches (out of a total of 75), there were no toxicities postrotation at one week. Rotations to methadone appeared to be associated with more postrotation adverse events.
The results of this study suggest that opioid rotation can be effective for pain management and the reduction of opioid-associated toxicities in most patients. Rotations to methadone appeared to be associated with more toxicities than rotations to other medications.
In patients with severe cancer-related pain, opioid rotations may be beneficial for improving pain management and addressing opioid-related toxicities. However, the duration of this effect is not clear. These results suggest that switching to methadone might not be the best choice for reducing toxicities.
Gong, S., Sheng, P., Jin, H., He, H., Qi, E., Chen, W., . . . Hou, L. (2014). Effect of methylphenidate in patients with cancer-related fatigue: A systematic review and meta-analysis. PloS One, 9(1), e84391.
To assess the safety and efficacy of methylphenidate for cancer-related fatigue. Secondary outcomes included depression, cognition, and adverse effects.
TYPE OF STUDY: Meta-analysis and systematic review
DATABASES USED: PubMed. EMBASE, PsycINFO, Cochrane Collaboration
KEYWORDS: Methylphenidate, dimethylphenidate, Ritalin, cancer, fatigue, asthenia, tiredness, and randomized controlled trial
INCLUSION CRITERIA: Randomized controlled trials, adults older than 18 years, the trial examined efficacy of methylphenidate on fatigue, and results were sufficient to calculate effect sizes
EXCLUSION CRITERIA: None specified
TOTAL REFERENCES RETRIEVED: N = 374
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: The Jadad scale was used for quality assessment.
PHASE OF CARE: Multiple phases of care
Meta-analysis was done with studies grouped according to the measure of fatigue that was used. In studies using the FACT-F (three studies), results showed a favorable effect of methylphenidate with a mean difference of -3.13 and a signficant overall effect (p -0.01). In studies using the BFI, results showed a favorable effect with mean difference of -0.69, but the Z test of overall effect was not significant. Methylphenidate had no effect on depression (two studies) or cognitive impairment (two studies). Studies varied widely in terms of the duration of treatment. Treatment for greater than four weeks was superior compared to placebo. However, treatment for less than four weeks did not show a significant effect compared to placebo. Rates of adverse effects between those getting methylphenidate and those getting a placebo were not significantly different. Those receiving methylphenidate had significantly more vertigo, anxiety, and nausea.
Results suggest that treatment with methylphenidate for at least four weeks is effective in reducing cancer-related fatigue and is not associated with a high rate of adverse effects. Treatment with methylphenidate did not improve depression or cognitive impairment. Use of different methods of measurement of fatigue showed different results.
Few studies were included, and some of these had very small sample sizes. Included studies did not provide sufficient information on relevant concomitant conditions of patients, such as sleep disorders and anxiety. Dosages and dosage increase approaches with methylphenidate varied.
Findings suggest that treatment with methylphenidate for at least four weeks can be helpful in managing cancer-related fatigue. However, the most appropriate dosages are not clear. Patients can experience side effects, and if methylphenidate is used, nurses need to monitor patients for side effects. Further large studies are needed to strengthen evidence related to effects and side effects of methylphenidate.
Gonella, S., di Pasquale, T., & Palese, A. (2015). Preventive measures for cyclophosphamide-related hemorrhagic cystitis in blood and bone marrow transplantation: An Italian multicenter retrospective study. Clinical Journal of Oncology Nursing, 19, E8–E14.
To determine the incidence of early onset hemorrhagic cystitis (EOHC) and identify the effectiveness of preventive measures upon EOHC
This retrospective study evaluated the effects of hyperhydration, diuresis alkalization, mesna, fluoroquinolone antibiotic prophylaxis, urethral catheterization, and CBI on 158 patients in two centers undergoing BMT regime upon EOHC. EOHC was defined as HC occurring within the 21 days after transplantation.
Groups were compared using the Mann-Whitney U test (for continuous variables) and Yates’ correction (for categorical variables). Logistic regression was used to identify factors contributing to the development of EOHC, including gender, age, smoking habits, type of transplantation, stem-cell donor, Cytoxan dose, urethral catheterization, and CBI. A multivariate regression model using a backward stepwise selection algorithm was employed.
Thirty-one patients (all allogeneic transplantations) developed EOHC. Female gender (p = 0.24) and the dose of cytoxan (p = 0.016) were identified as independent risk factors for EOHC. The daily dose of mesna was the only significant measure (p = 0.01) identified between those who developed EOHC (median = 4.463) and those who did not (3.701).
Univariate analysis does not support the current standard, prophylactic catheterization and CBI, for prevention of EOHC. The best practice includes hyperhydration association with diuresis alkalization and mesna infusions.
Nurses caring for patients at risk of HC may need to reassess current standards for prophylactic treatment of HC.
Gonella, S., Garrino, L., & Dimonte, V. (2014). Biofield therapies and cancer-related symptoms: A review. Clinical Journal of Oncology Nursing, 18, 568–576.
PHASE OF CARE: Active antitumor treatment
APPLICATIONS: Palliative care
Interventions considered to be BT were healing touch, Reiki, and therapeutic touch. The effect on pain was examined in seven studies. There were some mixed findings, but most showed a reduction in pain over short time periods. Fatigue was assessed in five studies. These demonstrated fatigue reduction post-treatment, but data were conflicting over a longer period of four to eight weeks. Anxiety and depression were examined in seven studies. All but one found a significant reduction in mood disorders, but a study comparing Reiki, sham Reiki, and usual care found no difference between the sham and actual Reiki groups. Most studies were of descriptive or quasi-experimental design; potential confounding variables were not examined, and placebo effects could not be ruled out.
Studies using biofield therapies for relief of pain, anxiety, fatigue, and depression generally showed benefit; however, the evidence is not strong due to the limitations of the studies included.
Low-quality design studies and the short duration of study follow-up
BT therapies have not demonstrated effectiveness in well-designed clinical studies; however, though it is weak, evidence suggests potential benefit. There were no adverse effects of these interventions reported. Biofield therapies are not expensive and are low-risk, so they can be considered in the management of cancer-related symptoms. Well-designed clinical trials are needed to establish efficacy.
Gomutbutra, P., O'Riordan, D.L., & Pantilat, S.Z. (2013). Management of moderate-to-severe dyspnea in hospitalized patients receiving palliative care. Journal of Pain and Symptom Management, 45, 885–891.
To describe the management of moderate to severe dyspnea in patients receiving palliative care
A retrospective study was conducted using the records of patients who were consulted by a palliative care service over a five-year period. Information about medications prescribed was collected for patients who self-reported moderate to severe dyspnea at their initial evaluations by the palliative care service. Follow-up assessments of dyspnea were conducted by the palliative care service within 24 hours of the initial assessment. Data extraction was completed by a physician.
Retrospective chart review of patients with moderate or severe dyspnea
Most patients reported an improvement in dyspnea within of 24 hours after palliative care service consultation. Most patients with dyspnea received opioids but only the combination of benzodiazepines and opioids was independently associated to improve dyspnea.
Because dyspnea is a common symptom in patients receiving palliative care, the authors conducted a study that reviewed the records of patients with moderate or severe dyspnea. The study found that opioids given with benzodiazepines were associated with improvements in dyspnea. Additional research to determine whether the use of benzodiazepines alone or in combination with opioids is more effective is necessary to to lead to improvements in dyspnea treatments.
Gomez-Hernandez, J., Orozco-Alatorre, A.L., Dominguez-Contreras, M., Oceguera-Villanueva, A., Gomez-Romo, S., Alvarez Villaseñor, A.S., . . . Gonzalez-Ojeda, A. (2010). Preoperative dexamethasone reduces postoperative pain, nausea and vomiting following mastectomy for breast cancer. BMC Cancer, 10, 692.
To evaluate the effectiveness of preoperative dexamethasone in reducing postoperative nausea, vomiting, and pain after mastectomy
Patients were randomized to receive either IV dexamethasone 8 mg or placebo 60 minutes prior to skin incision. All patients had the same standardized general anesthesia. The same surgical team performed each surgery. Pain was assessed on entry to the recovery room and at 6, 12, and 24 hours postoperatively. Analgesia was ketorolac 30 mg every 8 hours and IV tramadol infusion 50 mg as backup medication. Patients were followed for up to 30 days after surgery.
Double-blinded placebo-controlled randomized trial
Compared to patients in the placebo group, those receiving dexamethasone had significantly lower pain scale scores immediately after surgery (p = 0.004), at 6 hours (p < 0.0005), and at 12 hours (p = 0.04). Pain score differences between groups were approximately 1 point at these times. Authors noted no differences between groups at 24 hours after surgery. More patients in the placebo group than in the dexamethasone group required analgesics (p = 0.008), and the mean dose of IV tramadol was lower for those who received dexamethasone (p = 0.03). Incidence of nausea and vomiting was lower with dexamethasone; more patients in the placebo group required antiemetics (p = 0.01)
Compared to preoperative administration of placebo, preoperative administration of dexamethasone was associated with less short-term postoperative pain, nausea, and vomiting.
Findings suggest that preoperative dexamethasone administration can reduce short-term postoperative pain, nausea, and vomiting. In this study patients received specific anesthesia regimens. Findings may not be the same with different anesthetics. Further study in this area should identify optimal management of postoperative symptoms. The administration of a single corticosteroid dose prior to surgery can be a relatively low-risk intervention that seems to improve the patient’s experience.
Gomes, M.Z., Jiang, Y., Mulanovich, V.E., Lewis, R.E., & Kontoyiannis, D.P. (2014). Effectiveness of primary anti-Aspergillus prophylaxis during remission induction chemotherapy of acute myeloid leukemia. Antimicrobial Agents and Chemotherapy, 58, 2775–2780.
To analyze risk factors for breakthrough invasive fungal infection (IFI) in patients receiving remission-induction chemotherapy and evaluate effects of echinocandin versus triazole prophylaxis
Data were obtained from patients’ electronic medical records for antifungal use, documented IFI, type of chemotherapy, use of HEPA air filtration, duration of hospitalization, and neutropenia and mortality. Kaplan-Meier curves were used to estimate the probability of remaining IFI free based on prophylaxis strategy. Patient data were used up to IFI diagnosis, loss to follow-up, death, or completion of 120 days post-induction, whichever came first.
Those receiving echinocandin versus mold active triazole had higher incidence of IFI (0% in the triazole group, 8% in the echinocandin group, p = 0.09). All cause mortality did not differ between groups. Regimens containing clofarabine for induction was also an independent predictor of IFI (p = 0.004). Patients who died within 120 days of beginning induction chemotherapy were more likely to be female, had prior chemotherapy-related AML, had lung disease or infection, or had cardiovascular disease as a comorbid condition. Those receiving echinocandin also had more breakthrough yeast infections.
Findings suggest that primary antifungal prophylaxis during remission induction with echinocandin may be less effective in preventing IFI than prophylaxis with mold-active triazoles.
Patients with AML undergoing remission-induction chemotherapy are at high risk for developing IFIs, particularly mold infections. Findings from this study suggest that the class of antifungal prophylaxis agent used influences the patient’s risk of IFI. Nurses should be aware of the potential increased risk for fungal and yeast infections in patients getting echinocandin prophylaxis. Further research in this area is warranted given the limitations of this study.
Gomes, B., Calanzani, N., Curiale, V., McCrone, P., & Higginson, I.J. (2013). Effectiveness and cost-effectiveness of home palliative care services for adults with advanced illness and their caregivers. Cochrane Database of Systematic Reviews, 6, CD007760.
STUDY PURPOSE: To review the evidence regarding effectiveness of home palliative care services for patients and their caregivers
TYPE OF STUDY: Meta-analysis and systematic review
DATABASES USED: 12 electronice databases were searched up to November 2012—Cochrane Central Register of Controlled Trials (CENTRAL); EMBASE; MEDLINE; Cochrane Pain, Palliative, and Supportive Care (PaPaS) Trials Register; Cochrane Effective Practice and Organisation of Care (EPOC) Trials Register; CINAHL; EURONHEED; PsycINFO; Cochrane Database of Systematic Reviews (CDSR); Database of Abstracts of Reviews of Effectiveness (DARE); Health Technology Assessment (HTA) Database; and NHS Economic Evaluation Database (NHS EED)
KEYWORDS: An extensive listing of search strategies is provided.
INCLUSION CRITERIA: Randomized controlled trials, time series, and pre-post trials; patients older than 18 years and/or their caregivers
EXCLUSION CRITERIA: Services provided in settings other than the home
PHASE OF CARE: End-of-life care
APPLICATIONS: Palliative care
Strong evidence suggests that home palliative care services increase the likelihood of patients dying at home and decrease symptom burden for patients. Evidence regarding effects for caregivers is conflicting and inconclusive. Evidence regarding cost and cost-effectiveness is insufficient to draw conclusions.
Findings provide strong evidence that home palliative care services result in increased deaths at home and reduced symptom burden for patients. The effect for informal caregivers is uncertain. Caregiver burden can be higher in situations with more patient symptoms to manage, so one could expect that reducing patient symptom burden could have some benefit for the caregiver.