Weber, J.S., Kahler, K.C., & Hauschild, A. (2012). Management of immune-related adverse events and kinetics of response with ipilimumab. Journal of Clinical Oncology, 30, 2691–2697.
RESOURCE TYPE: Expert opinion
PHASE OF CARE: Multiple phases of care
Expert opinion level information only
Nurses need to educate patients that it may take a long time to see a tumor response from treatment, and also that adverse events can occur a relatively long time after treatment. Patients need to know to promptly report events that occur weeks and months after treatment and that ongoing patient follow-up to assess for and manage any adverse events is critical. In most cases, management of treatment-related symptoms involves the administration of systemic corticosteroids for persistent or severe symptoms.
Weber, J., Thompson, J.A., Hamid, O., Minor, D., Amin, A., Ron, I., . . . O'Day, S.J. (2009). A randomized, double-blind, placebo-controlled, phase II study comparing the tolerability and efficacy of ipilimumab administered with or without prophylactic budesonide in patients with unresectable stage III or IV melanoma. Clinical Cancer Research, 15, 5591–5598.
To determine the usefulness of budesonide as a premedication to ipilimumab in the prevention of diarrhea caused by immune response to this agent
Double-blind, randomized study to receive or not to receive budesonide (placebo) with ipilimumab. Patients were randomized 1:1 to receive concomitant oral budesonide or placebo with open-label ipilimumab administered 10 mg/kg by 90-minute infusions at weeks 1, 4, 7, and 10. Oral budesonide 9 mg or placebo was self-administered daily until week 12, then tapered until discontinuation at week 16. Patients who developed grade 2 diarrhea or greater or other immune-related adverse events discontinued budesonide/placebo and commenced open-label budesonide/steroids. Patients with grade 2 diarrhea lasting for two weeks despite concomitant therapy or with grade 3 or 4 diarrhea discontinued ipilimumab.
PHASE OF CARE: Active antitumor treatment
Common Terminology Criteria for Adverse Events (CTCAE), version 3.0
CTCAE, version 3.0
The rate of grade 2 or greater diarrhea was similar between the two groups. Twenty-eight percent of the group with budesonide and 32% of the group with placebo experienced one event of grade 2 or greater diarrhea. No patients experienced more than two events. The side effects were similar in the budesonide and placebo arms. Ninety percent of patients with budesonide and 95% of those with placebo had drug-related adverse events of any grade. Diarrhea and autoimmune hepatitis were the most common adverse events. Adverse events in 26% with budesonide and 32% with placebo lead to treatment discontinuation.
Budesonide did not alter the rate of grade 2 or greater diarrhea, nor did it improve tolerability in patients receiving ipilimumab. The conclusion of the authors was that budesonide should not be used to prevent grade 2 or greater diarrhea. Systemic steroids were used to treated immune-related adverse events. No evidence showed that systemic steroids altered the activity of ipilimumab.
Ipilimumab is an immunotherapy that has immune-related side effects, which are managed differently than the side effects of chemotherapy agents. Nurses need to be aware of these side effects and report them to practitioners (physician or advanced practice providers) for management (most commonly steroid management).
Weber, B.A., Roberts, L., Yarandi, H., Mills, T.L., Chumbler, N.R., & Wajsman, Z. (2007). The impact of dyadic social support on self-efficacy and depression after radical prostatectomy. Journal of Aging & Health, 19(4), 630–645.
To assess the effect of one-on-one peer support on enhancing self-efficacy and decreasing depression in men undergoing radical prostatectomy for prostate cancer
A core group of support partners who were prostate cancer survivors were recruited for the study protocol and trained to recognize signs and symptoms of clinical depression, communicate with active listening skills, and record reactions of study participants in a weekly log. One-on-one sessions were held in a private location, without involvement of patient's significant others. Men were randomly assigned to the support intervention or usual care. Support sessions were to be done eight times over an eight-week period. Data were collected at baseline and at four and eight weeks.
Randomized controlled trial
The number of sessions was 1–8. Those in the treatment group had significantly higher self-efficacy (p = 0.005) and lower depression (p = 0.032) at eight weeks. All patients had low depression scores at baseline. There was an 8.6% drop-out rate.
The support intervention provided by trained prostate cancer survivors demonstrated a positive effect on patient self-efficacy and depression scores.
Study findings show a positive effect of one-on-one support among men with prostate cancer when support was provided by prostate cancer survivors who had the same treatments, side effects, and experiences. It has been suggested that men do not tend to participate in support groups, being less inclined to share concerns in a support-group setting. One-on-one pairing, one patient with one individual who has had similar experiences and adjusted well, may be very beneficial to patients.
Warr, D.G., Street, J.C., & Carides, A.D. (2011). Evaluation of risk factors predictive of nausea and vomiting with current standard-of-care antiemetic treatment: analysis of phase 3 trial of aprepitant in patients receiving adriamycin-cyclophosphamide-based chemotherapy. Supportive Care in Cancer, 19, 807–813.
Whether prognostic factors in nausea and vomiting can be used to identify a low-risk group for whom ondansetron plus dexamethasone alone would provide a high level of protection (defined as 80% or less of no emesis) and to evaluate the impact of the neurokinin 1 (NK1) receptor antagonist aprepitant on chemotherapy-induced nausea and vomiting (CINV), regardless of the antiemetic risk
This was a multisite study.
All patients were in active treatment.
This was a phase III, multicenter, randomized, double-blind, parallel-group, placebo-controlled trial evaluating women with breast cancer who were receiving their first anthracycline plus cyclophosphamide-based chemotherapy regimen.
The most significant factor that had an impact on incidence of vomiting was treatment with aprepitant (p = 0.0001). Age over 55 years (p = 0.006), alcohol use (p = 0.005), and no history of morning sickness (p = 0.0007) were all associated with decreased risk. Motion sickness was not predictive of emesis.
The study's overall recommendation was to use the best available antiemetic regimen from the first cycle to maximize control of CINV and minimize anticipatory nausea and vomiting in subsequent cycles.
Aprepitant use ameliorated the risk of emesis associated with age, alcohol use, and previous history of morning sickness.
The study only looked at patients with breast cancer receiving anthrocycline-containing chemotherapy regimens with cyclophosphamide. Only two men were included in the study. The results are not generalizable to all patients with cancer.
Expansion of this study to include all cancer types and evaluate emetogenic potential with consideration of risk factors would be useful. This study demonstrates the importance of risk analysis when choosing antiemetics, but it also shows the clear benefit of using aprepitant in this group.
Ward, S.E., Wang, K.K., Serlin, R.C., Peterson, S.L., & Murray, M.E. (2009). A randomized trial of a tailored barriers intervention for Cancer Information Service (CIS) callers in pain. Pain, 144(1–2), 49–56.
To test the efficacy of a tailored intervention regarding patient barriers to pain management and pain duration, pain severity, and pain-related interference with daily life
Patients who called the Cancer Information Service and reported moderate to severe pain were asked to stay on the line and queried about consent for study participation. Consenting participants were randomized to one of three groups: the control group, which responded to a single-item screening measure regarding pain and received no intervention; the assessment-only group, which responded to all baseline assessment measurement tools and provided follow-up outcome measures but received no intervention; or the experimental group, which received the intervention. The intervention consisted of determination of barriers, as measured by a standardized assessment, and delivery of a standardized scripted message relating to each barrier identified. Pain duration, pain severity, pain-related interference with life, and barriers were assessed at baseline, during the initial telephone call, and via a follow-up call approximately 28 days after the intervention. Analysis compared the cost of the intervention to the cost of the assessment-only group. Supervisory staff monitored 10% of calls for general quality control regarding eligibility and invitation to participate. Staff who made the follow-up phone calls, to measure outcomes, were blinded to study-group assignment.
Randomized three-group study
The targeted telephonic intervention had a positive impact on attitudinal barriers to pain management but had no impact on other pain-related outcomes. In regard to effect on barriers, results were similar in the assessment-only and intervention groups.
Providing telephonic assessment of patient barriers to pain management and information about pain management are effective means of reducing those barriers. The effectiveness of the specified interventions and the effect of barrier reduction on overall pain control and management remains unclear.
Ward, S.E., Serlin, R.C., Donovan, H.S., Ameringer, S.W., Hughes, S., Pe-Romashko, K., & Wang, K.K. (2009). A randomized trial of a representational intervention for cancer pain: Does targeting the dyad make a difference? Health Psychology: Official Journal of the Division of Health Psychology, American Psychological Association, 28(5), 588–597.
To test the effectiveness of the RIDcancerPain program at overcoming attitudinal barriers to pain management among patients; to determine if the program is more effective when delivered to a patient with a significant other present than to a patient without a significant other present
Patients were blocked by setting (teaching vs. nonteaching facility) and then randomized to one of three study conditions: the dyad, in which both the patient and a significant other received the educational intervention; the solo condition, in which the patient received the intervention without a significant other present; and the care-as-usual condition. The RIDcancerPain intervention consisted of seven elements:
In the solo condition, the significant other was asked to leave the room during the intervention. In the dyad condition, the intervention was provided to both individuals. In the care-as-usual condition, project staff answered the questions that participant pairs had about the project. Measurement was done at baseline (T1), at five weeks (T2), and at nine weeks (T3).
Randomized single-blind controlled trial
This intervention did not result in a significant effect regarding pain management or barrier reduction. Whether the patient received the intervention with a significant other present did not seem to affect the result of the intervention.
Findings suggest that the authors' hypothesis—that RIDcancerPain intervention changes attitude, which in turn affects pain outcomes—oversimplifies pain management.
Ward, S., Donovan, H., Gunnarsdottir, S., Serlin, R.C., Shapiro, G.R., & Hughes, S. (2008). A randomized trial of a representational intervention to decrease cancer pain (RIDcancerPain). Health Psychology: Official Journal of the Division of Health Psychology, American Psychological Association, 27(1), 59–67.
To determine if the changes associated with the RIDcancerPain program—in regard to beliefs, coping, pain severity, and pain-related interference—are greater than the changes associated with standard education
Subjects were randomized to the control group or the intervention group. The control group received attention and standardized information about pain. Information was basic. The control group received a booklet, in question-answer format, that provided a review of common misconceptions about pain and information about managing the side effects of opioids. The intervention consisted of one session. Coverage of each subject during the session lasted 20–60 minutes. Patients were asked to describe beliefs about cancer pain (cause, timeline, consequences, cure, and control). The intervener identified and discussed misconceptions, provided accurate information, and cited the benefits of implementing changes based on the information provided. Patients discussed misconception-related limitations and losses. After the intervention (2–3 days later), patients in the intervention group had the opportunity to ask questions and provide comments via telephone, in a conversation with the research nurse. Patient-related baseline measures were gathered by means of self-report questionnaires that had been mailed to the patient prior to the intervention. Measures were also gathered at 1 and 2 months.
Randomized controlled trial
The RIDcancerPain intervention reduced measured patient barriers to pain management and usual pain severity but demonstrated no effect on other measures of pain severity, coping, pain-related interference with life, or overall well-being.
Findings suggest that providing the information specified in the RIDcancerPain program can be beneficial in terms of overcoming known barriers to effective pain management. However, the effect of the program on overall pain control remains unclear: Findings suggest that time and attention may be the most important factors in dealing with barriers to pain management. (In the intervention group, the period in which effects were greatest was shortly after individualized sessions and follow-up calls.)
Ward, E., Smith, M., Henderson, M., Reid, U., Lewis, I., Kinsey, S., et al. (2009). The effect of high-dose enteral glutamine on the incidence and severity of mucositis in paediatric oncology patients. European Journal of Clinical Nutrition, 63(1), 134-140.
To determine if 0.65 g/kg enteral glutamine daily for 7 days is effective in reducing the incidence and severity of mucositis in pediatric oncology patients when given with chemotherapy
Patients received one course of chemotherapy with glutamine and an identical course without. Alternate patients were given glutamine with course 1 or with course 2.
The study was conducted at a single site at Yorkshire Regional Centre for Pediatric Oncology and Hematology in the United Kingdom.
Patients were undergoing the active treatment phase of care.
This was a randomized study using the patients as their own controls.
No difference was found between the five symptoms or for the total number of children with each symptom.
Oral glutamine did not improve the nutritional status of patients in the study. Even though subjective toxicity scores showed more problems if glutamine was not used, because of the small sample size, the difference was not significant. In addition, 62% took glutamine via enteral feeding tube, therefore eliminating the local effect on the oral mucosa.
Further study into what factors resulted in the decreased use of TPN could be of benefit. Further studies are needed to investigate the use of oral glutamine using larger and more diverse populations.
Wardrop, D., Estcourt, L.J., Brunskill, S.J., Doree, C., Trivella, M., Stanworth, S., & Murphy, M.F. (2013). Antifibrinolytics (lysine analogues) for the prevention of bleeding in patients with haematological disorders. The Cochrane Database of Systematic Reviews, 2013(7).
TOTAL REFERENCES RETRIEVED: 470
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Several authors were involved in the review. The initial search was completed by one author; subsequently, two authors performed a secondary screening of identified studies. Lastly, two authors, using the Cochrane “risk of bias” tool, evaluated the remaining studies. Meta-analysis was not done given the heterogeneity of the data.
PHASE OF CARE: Transition phase after active treatment
APPLICATIONS: Pediatrics, elder care
The authors determined the evidence for efficacy (prevention of bleeding) and safety (lack of thrombosis) to be low-grade. Three studies demonstrated a reduced risk of bleeding, a reduction in platelet transfusion, and a lack of development of thromboembolism.
The findings suggest that antifibrinolytics may reduce bleeding and the need for platelet transfusions. There was no evidence for an increased risk of blood clots secondary to antifibrinolytics. Whether the antifibrinolytics reduced the need for other types of transfusions is unclear. The findings support the need for larger trials.
The small sample size was deemed to be below the optimal information size, and thus is a major limitation.
Nurses are involved in the care of patients with hematologic malignancies at risk of bleeding. It is imperative that nurses become knowledgeable regarding the use of agents that may mitigate this risk.
Wannesson, L., Luthi, F., Zucca, E., Rosselet-Christ, A., Baglioni, M., Marelli, L., . . . Ketterer, N. (2011). Pegfilgrastim to accelerate neutrophil engraftment following peripheral blood stem cell transplant and reduce the duration of neutropenia, hospitalization, and use of intravenous antibiotics: a phase II study in multiple myeloma and lymphoma and comparison with filgrastim-treated matched controls. Leukemia and Lymphoma, 52, 436–443.
To explore the efficacy of pegfilgrastim to accelerate neutrophil engraftment following stem cell autotransplant.
Patients were given pegfilgrastim 6 mg subcutaneously the day after autologous peripheral stem cell transplant (ASCT). Controls, who were matched for age, gender, disease, high-dose chemotherapy regimen, peripheral blood stem cell dose, and number of prior therapy lines, received filgrastim beginning five to seven days (median = 7) posttransplant. Filgrastim therapy continued daily for 4 to 10 (median = 6.5) doses.
Patients were undergoing the active treatment phase of care.
This study was a matched control clinical trial.
Time to neutrophil engraftment was defined as the time to the first of three consecutive days of an absolute neutrophil count (ANC) greater than or equal to 0.5x109/L. No specific measurement tools were used other than checking laboratory values.
The pegfilgrastim group had a significantly shorter median time to neutrophil engraftment than the filgrastim group (9.5 versus 11 days, respectively; p < 0.0001), median duration of neutropenia (6 versus 7 days, respectively; p = 0.0001), median duration of intravenous antibiotic therapy (4 versus 6.5 days, respectively; p = 0.0007), and median hospitalization duration (13 versus 14 days, respectively; p=0.0184). The pegfilgrastim and filgrastim groups had a similar median time to platelet engraftment (11.5 versus 11 days, respectively; p=0.42) and median duration of fever (3 versus 3 days, respectively; p=0.35). The two groups required an equal number of red blood cell and platelet transfusions.
Treatment with pegfilgrastim started the day after ASCT results in earlier neutrophil engraftment and reduced neutropenia compared to patients who received filgrastim beginning five to seven days posttransplant. These differences were more pronounced in patients with multiple myeloma than in those with lymphoma, suggesting that interventions may need to be adjusted based on diagnosis.
Infection is a potentially life-threatening risk of ASCT. The longer the period of time between chemotherapy-induced pancytopenia and neutrophil engraftment, the greater the risk. Findings suggest that pegfilgrastim may be more effective with a single injection rather than multi-day injections with filgrastim.