Van Dalen, E.C., Mank, A., Leclercq, E., Mulder, R.L., Davies, M., Kersten, M.J., & Van de Wetering, M.D. (2016). Low bacterial diet versus control diet to prevent infection in cancer patients treated with chemotherapy causing episodes of neutropenia. Cochrane Database of Systematic Reviews, 4, CD006247.
STUDY PURPOSE: To determine the efficacy of a low bacterial diet (LBD) versus a control diet in preventing infection and in decreasing infection-related mortality in adult and pediatric patients with cancer receiving chemotherapy that causes episodes of neutropenia
TYPE OF STUDY: Meta-analysis and systematic review
DATABASES USED: CENTRAL (2015, Issue 4), DARE (2015, Issue 4), PubMed (from 1946 to May 2015), EMBASE (from 1980 to May 2015), CINAHL (from 1981 to May 2015), reference lists of relevant articles and conference proceedings of the American Society of Hematology (ASH) (from 2000 to 2015), European Bone Marrow Transplantation (EBMT) (from 2000 to 2015), Oncology Nursing Society (ONS) (from 2000 to 2015), International Society for Paediatric Oncology (SIOP) (from 2000 to 2014), Multinational Association of Supportive Care in Cancer (MASCC) (from 2000 to 2015), ASCO (from 2000 to 2015), ICAAC (from 2000 to 2015), European Society for Clinical Nutrition and Metabolism (ESPEN) (from 2000 to 2015), American Society for Parenteral and Enteral Nutrition (ASPEN) (from 2000 to 2015), European Hematology Association (EHA) (from 2000 to 2015), National Institutes of Health Register via clinicaltrials.gov (May 2016), International Standard Randomized Controlled Trial Number (ISRCTN) Register
INCLUSION CRITERIA: Randomized, controlled trials (RCTs) comparing the use of an LBD versus a control diet in regard to infection rate
EXCLUSION CRITERIA: None stated
No evidence suggests that a LBD decreases the incidence of infection in patients undergoing chemotherapy who experience neutropenia. However, the evidence was not robust enough for the authors to conclude that no benefit existed, so the possibility of benefit/no benefit was inconclusive.
A LBD is not recommended for patients undergoing chemotherapy who experience episodes of neutropenia. Further research is indicated to conclude that no benefit exists.
Valeriani, M., Scaringi, C., Blasi, L., Carnevale, A., De Sanctis, V., Bonome, P., . . . Enrici, R.M. (2015). Multifraction radiotherapy for palliation of painful bone metastases: 20 Gy versus 30 Gy. Tumori, 101, 318–322.
To compare multifraction radiation therapy schedules for the palliation of pain from bone metastases
The medical records of patients treated with either 20 Gy in five fractions or 30 Gy in 10 fractions of radiotherapy were used for data collection. Pain was assessed prior to and one month after treatment. Clinical response was graded as complete response (CR, pain resolution), partial response (PR, reductions of at least two points on a numeric scale), or no response (NR). The two groups' outcomes were compared according to radiotherapy schedule.
Retrospective, descriptive study
The overall response rate was 88.9%. In the 30 Gy group, the CR rate was 19% compared to 6.5% in the 20 Gy group (p = 0.019). The PR rate in the 30 Gy group was 68.3% compared to 83.1% in the 20 Gy group. There was no difference between groups in overall response rates. The mean decline in pain score was 3.2 in the 20 Gy group and 3.6 in the 30 Gy group. More patients in the 30 Gy group had multiple sites of bone metastases. The incidence of toxicity was higher in the 30 Gy arm (p = 0.0001). The most common toxicities were nausea, vomiting, and diarrhea. In the regression analysis, incorporating variables of age, radiation therapy site, gender, tumor type, and analgesic use did not reveal a statistic difference in outcomes between the groups.
Optimal doses and fractionation for the palliation of bone metastases-related pain were not defined. This study demonstrated similar pain relief with a more abbreviated course of treatment, suggesting that a shorter treatment course may be as effective as long-course treatment for pain palliation. This may result in less toxicity from radiation treatment.
The findings of this study suggested that short-term radiation treatment for pain from bone metastases may be as beneficial as longer term treatment, and it may have fewer adverse side effects. Additional research to develop evidence for the most beneficial radiation schedule is needed.
Valcarcel, D., Sanz, M.A., Sureda, A., Sala, M., Munoz, L., Subira, M., et al. (2002). Mouth-washings with recombinant human granulocyte-macrophage colony stimulation factor (rhGM-CSF) do not improve Grade III-IV oropharyngeal mucositis (OM) in patients with hematological malignancies undergoing stem cell transplantation. Results of a randomized, double-blind, placebo-controlled study. Bone Marrow Transplantation, 29, 783-787.
Recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) mouthwash
400 mcg dissolved in 20 mL NS; control received 200 mL saline only
Mouthwashings 3 times a day for 30 min without swallowing, over a period of 5 days after inclusion in protocol. Avoid other oral intake for 1 hour.
Also standard protocol of mouth care – toothbrushing after each meal and rinsing oral cavity with 0.9% saline or in cases of inflammation, 0.12% chlorhexidine four times daily
Only MM patients received IV GCSF 5 mcg/kg from day +7 to neutrophil recovery.
The study was comprised of 41 patients (tx grp = 18, 23 placebo), with an age range of 16–69 years and a median age of 44.
All patients developed OM grade III-IV after auto- or allo-SCT.
Oct 1998 – Mar 2001
Prospective randomized, double-blind placebo-controlled study
WHO toxicity score grading mucositis from 0-4, EVA scale (visual analog) scoring swallowing induced pain from 0-10 3x a day, sleep quality evaluations as good, intermediate, and poor, and food intake, none, liquids, soft, regular
Also, infections, days with fever, fungal and viral oral infections, and need for broad spectrum antibiotics, TPN, and opioids were documented.
P < 0.05 = significant
No statistically significant differences in overall duration of mucositis or duration of maximum grade of OM. Mouth pain and sleep quality scores were similar.
More people in the rhGM-CSF group needed PCA morphine (50%, 8pts) versus the NS (10%, 2pts).
Also no significance in the use of TPN between the two groups.
Given cost, it appeared the results were not better than NS.
No benefit of GM-CSF mouthwash.
May actually show benefit of NS.
Schering-Plough supplied the rhGM-CSF.
Small diverse study group – long duration for study – other potential factors possibly change over time.
Study needs to be larger.
Only trialed with stem cell transplant recipients.
Patients were also rinsing with 0.9 NS and chlorhexidine as part of everyday mouth care (unable to determine number).
Study was from 1998-2001.
Study focused only on prevention after dev grade 3 – 4 OM.
Vahdat, L., Papadopoulos, K., Lange, D., Leuin, S., Kaufman, E., Donovan, D., . . . Balmaceda, C. (2001). Reduction of paclitaxel-induced peripheral neuropathy with glutamine. Clinical Cancer Research, 7, 1192–1197.
Female participants were were admitted for cyclophosphamide (6,000 mg/m²), thiotepa (500 mg/m²) and carboplatin (800 mg/m²) over 96 hours seven and four days prior to stem cell transplantation. Mesna (7,400 mg/m²; 1,500 mg/m² per day) was administered by continuous infusion over 120 hours. After December 1998, women enrolled in the study received glutamine (10 g orally three times daily) for four days starting 24 hours after the completion of paclitaxel. Data were collected at baseline and two weeks after completion of chemotherapy. In addition, paired pre- and post-paclitaxel evaluations were performed on all women.
Women who received glutamine had fewer symptoms, with 8% of women who received glutamine reporting dysesthesias in the fingers and toes, as compared to 40% of the women who did not receive glutamine. In addition, the frequency of moderate to severe numbness was observed less often in the glutamine-treated group than in the non-glutamine group for both fingers and toes. Moderate to severe parasthesias also were observed less frequently in those who received glutamine.
Vadiraja, H.S., Raghavendra, R.M., Nagarathna, R., Nagendra, H.R., Rekha, M., Vanitha, N., . . . Kumar, V. (2009). Effects of a yoga program on cortisol rhythm and mood states in early breast cancer patients undergoing adjuvant radiotherapy: A randomized controlled trial. Integrative Cancer Therapies, 8, 37–46.
To compare effects of an integrated yoga intervention with those of a brief supportive intervention on salivary cortisol levels and mood in patients with early breast cancer undergoing adjuvant radiotherapy
Patients were randomly assigned to a six-week yoga intervention or a control group. The yoga intervention included a set of asanas (postures), breathing exercises, meditation, and yogic relaxation techniques with imagery. Individual hour-long sessions were to be attended at least three times per week for six weeks during radiation treatments. These were administered by a trained yoga therapist. The control intervention was brief supportive therapy with education that was routinely offered to all patients. Control patients and caretakers underwent counseling sessions for 15 minutes every 10 days with a social worker as well. Study data were collected at baseline and at the end of the study period. Patients were asked to provide saliva samples three times per day for three consecutive days before and after radiotherapy. Specific procedures for saliva collection, storage, and immunoassay were followed.
Patients were undergoing the active treatment phase of care.
A randomized controlled trial design was used.
There were no significant effects of the yoga intervention on cortisol results overall; however, the mean pooled diurnal cortisol and 6 am cortisol levels were lower in the yoga group (p < 0.05). There were significant declines in anxiety levels in both groups. ANCOVA showed a significant decrease in reported anxiety in the yoga group compared to controls (p < 0.001). Depression declined in both groups over time. ANCOVA showed a significant decrease in reported depression in the yoga group compared to controls (p = 0.002). There was a significant decrease in perceived stress in the yoga group (p < 0.001), but not in the control group. Effect sizes seen were 0.31 for anxiety and depression scores and 0.36 for perceived stress.
Results suggest decreases in anxiety, depression, perceived stress, and 6 am and pooled mean cortisol levels with the yoga intervention used here.
Findings show that anxiety and depressive symptoms decline over time among patients in active treatment with adjuvant radiation therapy in women with breast cancer. Participation in stress reduction interventions, such as yoga, may augment this decline. Changes in cortisol findings seen here with yoga suggest that effects may be attributed to stress reduction, rather than attention, social support, and education alone. Further research in this area is warranted to determine efficacy of yoga in other patient groups, and association with other patient symptoms and problems associated with anxiety and depression.
Vadhan-Raj, S., Trent, J., Patel, S., Zhou, X., Johnson, M.M., Araujo, D., … Benjamin, R.S. (2010). Single-dose palifermin prevents severe oral mucositis during multicycle chemotherapy in patients with cancer: a randomized trial. Annals of Internal Medicine, 153, 358–367.
To evaluate the efficacy and safety of palifermin given as a single dose before each cycle in patients receiving doxorubicin-based multicycle chemotherapy
Patients were randomly assigned in a 2:1 ratio to receive palifermin or placebo.
This study was conducted at a single-site at the University of Texas M.D. Anderson Cancer Center.
Patients were undergoing the active treatment phase of care.
This was a randomized, double-blind, placebo-controlled trial.
Palifermin significantly reduced the incidence of moderate to severe (grade 2 or higher) mucositis (44% versus 88%; p <0.001) and severe mucositis (13% versus 51%; p < 0.002).
A single dose of palifermin before each cycle reduced the incidence and severity of mucositis. It also demonstrated effectiveness as secondary prophylaxis in a few patients with severe mucositis.
Mucositis and the pain it causes can significantly impact patients with cancer during treatment. Further research is needed to establish the alleviation of pain and the improved ability to drink, eat, and talk. If the mucosal lining is maintained, it would be important to establish if there are fewer infections, use of total parenteral nutrition (TPN) to maintain nutrition, and use of opiod patient-controlled analgesia (PCA) for pain control.
Vadhan-Raj, S., von Moos, R., Fallowfield, L.J., Patrick, D.L., Goldwasser, F., Cleeland, C.S., . . . Chung, K. (2012). Clinical benefit in patients with metastatic bone disease: Results of a phase 3 study of denosumab versus zoledronic acid. Annals of Oncology, 23, 3045–3051.
To compare the efficacy and safety of subcutaneous denosumab versus IV zoledronic acid for the treatment of established bone metastases
Patients were allocated to one of two treatment arms using a computer-generated randomization schedule with a permuted block size of 4. Randomization was stratified by tumor type, previous skeletal-related event (SRE), and systemic anti-cancer therapy. Daily calcium and vitamin D supplements were strongly recommended. Patients received either subcutaneous denosumab (120 mg) every four weeks or IV zoledronic acid (4 mg, dose adjusted for renal function) every four weeks for the treatment of established bone metastases.
Denosumab delayed time to first SRE or hypercalcemia of malignancy (19 months for denosumab versus 14.4 months for zoledronic acid) and reduced the risk of radiation to bone by 22%. Denosumab reduced the risk of a two-point increase (i.e., worsening) for the BPI worst pain rating by 15% relative to denosumab. Some evidence showed delay in the time to increased pain interference (6.5 months for denosumab versus 5.8 months for zoledronic acid). Both treatments were associated with the maintenance of health-related quality of life. For patients with an analgesic score of 2 or less (no or weak opioid use), fewer patients in the denosumab group than in the zoledronic acid group shifted to strong opioid analgesic use. On average, there was a 27% relative increase in the proportion of zoledronic acid-treated patients who initiated strong opioid analgesics compared with the denosumab-treated group.
The use of denosumab was associated with better prevention of SREs secondary to solid tumors or multiple myeloma compared to zoledronic acid. Denosumab also delayed pain progression and worsening of pain interference.
Skeletal pain is one of the most difficult to treat components of metastatic bone disease. In this study, differences were noted in pain, pain interference, and analgesic use between the treatment groups. Denosumab significantly delayed the worsening of pain and pain interference, as measured by the BPI.
Uzkeser, H., Karatay, S., Erdemci, B., Koc, M., & Senel, K. (2013). Efficacy of manual lymphatic drainage and intermittent pneumatic compression pump use in the treatment of lymphedema after mastectomy: A randomized controlled trial. Breast Cancer. Advance online publication.
To investigate efficacy and contribution of an intermittent pneumatic compression pump in lymphedema management and evaluation of measurement method correlation
Patients were randomized into two groups by consecutive alternating allocation by time of admittance. Group 1 received complete decongestive therapy (CDT) treatment (skin care, manual lymphatic drainage, compression bandage, compression garments, and exercise). Group 2 received CDT in combination with the intermittent pneumatic compression pump after manual drainage for 45 minutes at 40mmHg. Both groups were treated five times per week for three weeks for a total of 15 sessions. Measurements were obtained initially, post-therapy in week three, and one month postcompletion.
Significant correlation (p = 0.001) between dermal thickness with ultrasound and circumference of forearm measurement and water immersion measure method on forearm. Pre- and post-treatment measurements with both groups were significantly reduced, but no statistically significant difference between groups after therapy and one month later were noted.
CDT remains the standard treatment for lymphedema. The addition of the pneumatic pump to CDT yielded no significant improvement in lymphedema. Limitations included small sample size and no long-term follow-up. More prospective randomized studies are needed to evaluate potential efficacy of pneumatic pump and to correlate ultrasound measurement of dermal thickness with water immersion method on forearms.
Nurses should continue to focus on education for prevention and early intervention for lymphedema.
Uronis, H.E., Currow, D.C., McCrory, D.C., Samsa, G.P., & Abernethy, A.P. (2008). Oxygen for relief of dyspnoea in mildly- or non-hypoxaemic patients with cancer: A systematic review and meta-analysis. British Journal of Cancer, 98(2), 294-299.
The objective was to identify articles that evaluate the efficacy of oxygen therapy and medical air for the improvement of dyspnea in patients with cancer.
Databases searched were MEDLINE and EMBASE (1966-December 2006).
Search keywords were MeSH terms including dyspnea (dyspnoea) , oxygen, and palliative care and text words including oxygen, dyspnea, breathlessness, oxygen, and inhalation therapy.
Randomized controlled trials comparing oxygen and medical air in patients with cancer suffering from refractory dyspnea who do not qualify for home oxygen therapy were included.
Studies were excluded if
Studies also were excluded for \"other\" reason (e.g., study articles were not editorial or review article).
A total of 203 citations was reviewed with 54 full-text articles examined. None of the selected studies had evidence of calculations to claim adequate power to answer the questions defined. All five studies included in the analysis were blinded, randomized, controlled crossover trials. Each study was assigned a Jadad score in quality evaluation. External validity was assessed for subject description, detailed intervention description, and adequately reported dyspnea outcomes. Dyspnea ratings as assessed by the Modified Borg’s 0-10 numerical rating scale (NRS), 100 mm visual analog scale (VAS), or 300 mm VAS were converted to standardized mean differences (SMDs). When data pertaining to paired analyses were missing in two periods of crossover trials, standard errors were interpreted. P-values were used to estimate correlations between repeated outcomes when available and when unavailable, the lowest estimate from other studies was used. Meta-analysis was performed only on studies from which means and variances from for dyspnea measurements could be determined from published reports, and effect sizes were reported as SMD with 95% confidence intervals. Statistical significance was determined by a P < 0.05. If additional data were needed, authors were contacted.
Four studies focused on comparing oxygen versus medical air for dyspnea relief, while the fifth compared Heliox28 (an agent that contains 72% helium and 28% oxygen) with oxygen and medical air. In three studies, oxygen was delivered by nasal cannula, and in the other two by face mask. Doses of oxygen ranged from 3-5 L/min. Oxygen was administered at rest in three studies and during a six-minute walk test (6MWT) in two studies.
One hundred thirty-four were included in meta-analysis (148 were analyzed). Studies had a median of 33 participants, with a mean of 29.6 and range of 14-51. The median participant age was 65 years; 39% were female, and no data related to race or ethnicity were available. Subjects presented with the following malignancies: lung cancer (65%) or unspecified cancer with metastasis to lung (15%), breast cancer (5%), colon (3%), and other (i.e., lymphoma, melanoma, sarcoma, carcinoid, skin, bladder, and head and neck) (7%). Baseline oxygen saturation for four of the five was reported. Baseline dyspnea at rest, as provided by three of the studies, was 0 (modified Borg), 5 mm (NRS), and 59 mm by 100 mm (VAS).
Oxygen therapy was shown ineffective in the relief of dyspnea in mildly or non-hypoxemic patients with cancer (SMD = -0.09, 95% CI -0.22 to 0.04; P = 0.16). Sensitivity analysis on the three included studies for which patient data were available was stable. Conflicting results were reported in the two studies that compared the effect of oxygen therapy on exercise tolerance (via 6MWT), where one study (Ahmedzai et al., 2004) indicated a statistically significant increase in distance with oxygen (174.6 m; SD = 11.2) use over medical air (128.8 m; P < 0.01, SD = 10.3), while the other (Bruera et al., 2003) did not indicate a difference between use of oxygen (331.6 m; SD = 54.9) and medical air (330.7 m; SD = 57.9). Of the four out of five studies that provided data on still-blinded patient preference for oxygen versus medical air, two studies reported a statistically significant still-blinded patient preference for oxygen over medical air. Four out of five studies had poor quality of reporting and inadequate discussion of randomization and blinding methodology.
Oxygen therapy did not appear to relieve the overall sensation of dyspnea in patients with cancer who do not qualify for long-term home oxygen therapy.
Study limitations include small patient sample size (n = 148), and 65% of patients were diagnosed with lung cancer (which limits the generalizability of data from populations with a wider range of malignancies with other factors contributing to dyspnea).
Further research and evaluation still is indicated. Despite conflicting findings among studies related to patient preference and oxygen effect on endurance and the overall lack of support for oxygen therapy in palliation of refractory dyspnea in patients with cancer, the subjective/psychological nature of dyspnea indicates that oxygen therapy may provide a comforting sense of dyspneic relief in some populations if served as a supplement to other, more effective interventions.
Uronis, H.E., & Abernethy, A.P. (2008). Oxygen for relief of dyspnea: What is the evidence? Current Opinion in Supportive and Palliative Care, 2(2), 89-94.
The objective was to summarize and evaluate evidence for the use of oxygen for the relief of dyspnea, with particular focus on situations in which oxygen is not already funded via long-term oxygen treatment guidelines.
The literature reviewed in this manuscript was dated 1980-2008. Early articles were used to support conclusions in the four articles dated 2007 (3) and 2008 (1).
Based on their evaluation of a single systematic review and meta-analysis, no conclusive benefit of oxygen therapy was determined among the cancer population. The authors recommend the N of one methodology, where oxygen or air should be used on an individual basis for breathlessness at rest or with exercise. They advocate this oxygen trial start with short-burst oxygen and continued use for specific patients who report reduction in breathlessness, regardless of level of hypoxia. They term this palliative oxygen rather than treatment of hypoxia.