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.

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.

• N = 135 enrolled, 115 randomized patients received at least one dose of ipilimumab (58 in group with budesonide, 57 in placebo group)
• MEDIAN AGE = 58 years (budesonide) 61 years (placebo)
• MALES: 74%(budesonide), 67% (placebo); FEMALES: 26% (budesonide), 33% (placebo)
• CURRENT TREATMENT: Immunotherapy
• KEY DISEASE CHARACTERISTICS: Unresectable and measurable stage III or IV melanoma
• OTHER KEY SAMPLE CHARACTERISTICS: Patients with ocular melanoma were excluded. Patients could be previously treated or previously untreated. Patients with a life expectancy of four months or more and performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1. Excluded patients had active untreated central nervous system metastasis, other malignancies from which they were disease free for less than five years, autoimmune disease (including history of inflammatory bowel disease), receipt of investigational drugs within four weeks of stating protocol therapy, previous treatment with an anti-CTLA-4 antibody, and had used immunosuppression.

• SITE: Not stated/unknown   
• SETTING TYPE: Outpatient    
• LOCATION: Not stated

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).

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.

• The sample was composed of 72 participants.
• Mean patient age was 60 years, with an age range of 47–74 years.
• All participants were male.
• All participants had undergone prostatectomy at least six weeks prior to the study and had been diagnosed within three months of the study.
• Of participants in the intervention group, 80% were married; in the control group, 67.6% were married. Of all participants, 83% were white and 35% had at least a high school or technical school education.
   

• Single site
• Outpatient
• Florida, United States

• Phase of care: active antitumor treatment
• Clinical application: eldercare

Randomized controlled trial

• Geriatric Depression Scale
• Stanford Inventory of Cancer Patient Adjustment
• Modified Inventory of Socially Supportive Behaviors
• UCLA Prostate Cancer Index
   

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.

• The study had a small sample size, with fewer than 100 participants.    
• The study shows baseline sample and group differences of import.
• The study had a risk of bias due to no appropriate attentional control condition.
• Findings are not generalizable because
  • The study was limited to specific prostate cancer patients. 
  • At baseline, between groups there were substantial differences in depression scores and urinary and sexual functioning.
  • A larger proportion of control patients were married, which could have contributed to greater concerns regarding impotency and relationships than might have occurred in the intervention group.

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.

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 

• The study reported on 866 patients.
• Mean age was 53.1 years.
• The sample was 99.5% female and 0.5% male.
• All patients had been diagnosed with breast cancer, and 99% of the sample was receiving anthrocycline-based chemotherapy.
• To be included in the study, patients had to provide Informed consent, be naïve to emetogenic chemotherapy, have a predicted life expectancy of at least four months, and have a Karnofsky score of 60 or greater.

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.

• Patients used diaries to record occurrence of emetic episodes, use of rescue therapy, and daily ratings of nausea severity using a visual analog scale.
• The authors used logistical regression models to evaluate the impact of the number of risk factors on treatment outcomes.

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.

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.

• The sample was composed of 1,256 patients who were randomized; 332 patients were in the control group, 332 were in the assessment-only group, and 290 completed the intervention group.
• Mean patient age was 55.77 years. Age range was 39–89 years.
• Of all patients, 74.2% were female and 25.1% were male.
• To be eligible, patients had to state, during the initial telephone interview, that they had at least moderate pain. Of all patients, 63.7% had at least some college-level education; 77.6% were Caucasian and 13.5% were African American.

• Multisite
• Wisconsin

Randomized three-group study

• Single-item on a five-point Likert-type scale, to measure pain severity
• Brief Pain Inventory (selected items)
• Barriers Questionnaire (Short Form)

• In regard to barriers, there was no difference between control and assessment-only groups. The targeted intervention group had a significantly lower postintervention barriers score than did the assessment-only group (p = 0.000, d = 0.47).
• Authors observed no significant differences between groups in regard to pain severity, duration, or interference scores.
• Barriers scores were used in cost comparisons between the intervention and assessment-only groups. Comparisons revealed no differences in cost-effectiveness between these groups.

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.

• The study had a risk of bias due to no appropriate control group.
• The study design did not allow authors to determine if changes in other aspects of pain management may have affected results.

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.

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:

1. The patient was asked to describe beliefs regarding the cause, timeline, consequences, cure, and control of cancer pain.
2. The intervener addressed gaps, confusion, and misconceptions about using analgesics and reporting pain. Those present discussed the issues.
3. The patient discussed limitations and losses that result from the misconceptions.
4. The intervener provided information to fill gaps and eliminate confusion, using scripted messages about common attitudinal barriers.
5. The intervener summarized the benefits of adopting recommendations derived from the information.
6. The patient created a plan for changing the way he or she managed pain.
7. During a follow-up telephone consult 2–4 weeks after the first session, the intervener evaluated and revised the coping plan.

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).

• The sample was composed of 161 patients.
• Mean patient age was 58.54 years; age range was 20–85 years. Mean age of significant others was 55.58 years; age range was 18–85 years.
• Of all patients, 60.2% were female and 39.8% were male.
• In the dyad group, lung and breast cancers were the most frequent diagnoses; in the solo group, lung, breast, and gastrointestinal cancers were the most frequent; in the control group, gastrointestinal cancer was the most common. Of all patients, approximately 90% were Caucasian. More than 50% of patients had an annual income below $50,000. In the majority of cases, the significant other was the patient's spouse.

• Multisite
• Outpatient
• Midwest, United States

Randomized single-blind controlled trial

• Barriers Questionnaire, to measure attitudes about analgesic use
• Composite score of five items, on a five-point Likert scale, to measure pain severity (Items included amount of time in pain and usual, worse, least, and current pain intensity.)
• Brief Pain Inventory (Short Form), to measure pain-related interference with activities
• Functional Assessment of Cancer Therapy-General (FACT-G)
• European Organization for Research and Treatment quality of life questionnaire QLQ-C30, sections to measure pain relief (0 = no relief, 4 = complete relief)

• Before T2, 37 pairs dropped out of the study. Only 124 pairs completed the study through T2. Comparison of dropouts to others showed a significant difference in pain relief ratings (p = 0.02): Those who dropped out had higher pain relief scores.
• At T2 there were no differences in attitudinal barriers between the two intervention groups.
• Pain relief change was higher in the dyad condition than in the solo condition (p = 0.008). However, neither group differed significantly from the control group in regard to this outcome.
• There were no significant differences across study groups in barriers at five weeks. Analysis of variance demonstrated no main effects of the intervention over time. However, authors did note a significant intervention-mediator effect, between baseline and nine weeks, in regard to changes in barrier scores and pain relief (p = 0.026), patient interference (p = 0.003), and negative mood (p = 0.033).

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.

• The study had a limitation due to no appropriate control group and no attentional control for the care-as-usual group.
• The study had a large number of dropouts before completion of measures at nine weeks, so impacts over a long term could not be evaluated.
• Authors did not examine changes in analgesic medications. Changes in regimen may have affected results.
• Authors did not provide details about the care-as-usual situation. The report did not cite the amount of education and counseling this group received.

Findings suggest that the authors' hypothesis—that RIDcancerPain intervention changes attitude, which in turn affects pain outcomes—oversimplifies pain management.

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.

• The sample was composed of 176 patients.
• Mean patient age was 55.11 years (SD = 11.52 years).
• Of all patients, 57.4% were female and 42.6% were male.
• The most frequent diagnoses were breast, gastrointestinal, genitourinary, and gynecologic cancers. Of all patients, 64.8% did not have health problems other than cancer; 40.9% were receiving concomitant chemotherapy. Of all patients, 71% were married and 86.9% were Caucasian. Mean severity of pain at baseline was 4.17 on a 10-point scale.

• Multisite
• Outpatient clinic in Wisconsin

Randomized controlled trial

• Brief Pain Inventory (selected items relating to pain severity, pain-related interference with life, and beliefs about analgesic use)
• Pain management index in regard to adequacy of analgesic use (a Likert-type scale, 0–3, for rating usual pain during the past week)
• Quality of Life Index-Cancer Version

• Compared to patients in the control group, patients in the intervention group showed greater decreases in barriers across time (p = 0.0025), with an effect size (d) of 0.765. In the intervention group, barriers decreased from baseline to the first follow-up month but then increased between the first- and second-month follow-ups.
• There was a greater decrease in usual pain severity for patients in the intervention group (p = 0.0085). No other main effects in analysis of variance were shown in regard to the intervention.
• Both groups of subjects showed decreased barriers over time.
• Changes in pain severity and quality of life varied over time.
• Of all patients, 21% dropped out of the study after completion of baseline measures. Dropouts had higher pain severity than did others.
• Approximately 50% of subjects had adequate pain control according to severity measures at the time of study entry. Analysis of mediators of pain variables was inconclusive, demonstrating different apparent correlations at different points in time.

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.

• The study had a risk of bias due to no appropriate control group. The attentional control group did not receive the follow-up telephone  calls that the intervention group received.
• Authors provided no information about changes in analgesic regimen or other pain management approaches.
• One-tailed tests of significance were used. This is a procedure consistent with the directional hypothesis posed, but it makes achievement of statistical significance more likely.
• Authors provided no analysis of difference in subgroups of patients, based on adequacy of background pain control.

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.)

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 comprised of 76 patients, aged 1–21 years.
• The sample was 56% male and 44% female.
• Cancer diagnoses were acute myelogenous leukemia (AML), B-cell non-Hodgkin lymphoma (NHL), Ewing’s sarcoma/primitive neuroectodermal tumor (PNET), rhabdomyosarcoma, osteosarcoma, and other.

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.

• Patient/parent diaries were used from day 1-21 using Common Toxicity Criteria for nausea, vomiting, diarrhea, oral mucositis, and abdominal pain.   
• Plasma ammonia and glutamine levels were recorded.
• Clinical measurements of weight, height, percentage weight/height, mid-upper arm circumference, total parenteral nutrition (TPN) use, enteral feeding, and other complicatios that could affect eating tolerance during enteral feeding.

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.

• The sample size was small with fewer than 100 patients.
• The study lacked a placebo.
• A number of patients were unable to complete the study.
• Randomizing all potential patients was not possible because of the need to urgently start treatment for some patients.

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.

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.

• FINAL NUMBER STUDIES INCLUDED = 3
• TOTAL PATIENTS INCLUDED IN REVIEW = 86
• KEY SAMPLE CHARACTERISTICS: Sample sizes ranged from 12 to 56 patients of all ages published in the years 1983–1995. Patients included those with APL, acute leukemia, and de novo AML. Two studies compared TXA and placebo; one compared EACA and placebo.

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.

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.

• A total of 80 patients (62.2% male, 38.8% female) who received intervention (pegfilgrastim; N = 40) and matched controls (filgrastim; N = 40) were included.   
• Mean age was 52.8 years (range 21.3–70.6).
• Half of the patients in each group had multiple myeloma (n = 20) and half had lymphoma (n = 20). The lymphoma group was subdivided into Hodgkin lymphoma (pegfilgrastim group [n = 8], filgrastim group [n = 7]) and non-Hodgkin lymphoma (pegfilgrastim group [n = 12], filgrastim group [n = 13]).

• Multi-site  
• Inpatient   
• Switzerland

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.

• Toxicity outcomes were not compared between the pegfilgrastim- and filgrastim-treated groups.
• Small sample (<100)
• Pegfilgrastim was provided free of charge by the manufacturer. There was no cost difference analysis between the pegfilgrastim- and filgrastim-treated populations. 
• No blinding, with associated risk of bias
   

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.