Wehler, T.C., Graf, C., Mohler, M., Herzog, J., Berger, M.R., Gockel, I., ... Schimanski, C.C. (2013). Cetuximab-induced skin exanthema: Prophylactic and reactive skin therapy are equally effective. Journal of Cancer Research and Clinical Oncology, 139(10), 1667–1672.
To determine the effectiveness of several treatment options in decreasing cetuximab-induced skin exanthema in three study populations: the historic group (no standard skin treatment); the proactive skin therapy group; and the reactive skin therapy group
Retrospective analysis
Using this simple reactive skin protocol can prevent the exacerbation of cetuximab-induced follicular exanthema. This therapy can stabilize exanthema development. Results of the prophylactic skin treatment cohort showed equally effective, but not superior, results in preventing skin toxicity ≥ grade 2. Both groups B and C had lower therapy interruptions.
Nurses need to assess for exanthema, which generally develops within one to four weeks of initiating cetuximab. Prophylactic and reactive skin protocols are equally effective and may be easier to handle in practice. Both prophylactic and reactive skin treatments reduce higher grades of exanthema, which can lead to therapy cessation.
Webster, L., Jansen, J.P., Peppin, J., Lasko, B., Irving, G., Morlion, B., . . . Carter, E. (2008). Alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist for the treatment of opioid-induced bowel dysfunction: Results from a randomized, double-blind, placebo-controlled, dose-finding study in subjects taking opioids for chronic non-cancer pain. Pain, 137, 428–440.
To assess the effectiveness and safety of alvimopan, a peripherally acting mu-opioid receptor antagonist, in patients with noncancer pain and opioid-induced bowel dysfunction.
Patients were randomized to one of four groups: oral alvimopan 0.5 mg twice daily (n = 130), oral alvimopan 1 mg daily (n = 133), oral alvimopan 1 mg twice daily (n = 130), or placebo capsules (n = 129).
Patients were instructed to discontinue laxative use. Rescue laxative medication (bisacodyl 10-30 mg) could be taken if the patient experienced discomfort with no bowel movement (BM) for four consecutive days. An interactive voice response system via touch-tone telephone was used for number of BMs, associated symptoms, rescue laxative use, opioid consumption, and pain intensity.
This was a phase IIb, randomized, double-blind, placebo-controlled, parallel-group study.
Oral alvimopan increases the frequency of SBMs and improves symptoms in adults on opioid pain regimens.
Oral alvimopan may be effective for the treatment of opioid-induced constipation in patients taking opioids for chronic pain and may improve opioid-induced bowel dysfunction symptoms. Use of alvimopan does not appear to compromise analgesia or induce opioid abstinence. Additional study is necessary to look at efficacy with an oncology population and determine long-term efficacy, as well as an optimal dosing regimen.
Weber, J.S. (2012). Practical management of immune-related adverse events from immune checkpoint protein antibodies for the oncologist. American Society of Clinical Oncology Educational Book, 174–177.
RESOURCE TYPE: Expert opinion
DATABASES USED: Not included
INCLUSION CRITERIA: Patients treated with ipilimumab
PHASE OF CARE: Active antitumor treatment
Low grade diarrhea (grade 1) should be treated symptomatically using loperamide, oral hydration, and electrolyte substitution. A colitis diet is recommended. Persistent or higher-grade diarrhea, bacterial or parasitic infections, viral gastroenteritis, or the first manifestation of an inflammatory bowel disease should be ruled out by an exam. Oral diphenoxylate hydrochloride and atropine sulfate four times a day and budesonide 9 mg daily are recommended. An endoscopy is recommended. For grade 3 or 4 diarrhea, treatment with ipilimumab should be permanently discontinued, and IV steroids and replenishment of fluid and electrolytes IV should be administered.
The information included was recommended in 2012. Since then, much more has been learned about the treatment of immune-related side effects of checkpoint inhibitors. Steroids are started early. This information seems out of date, and a more recent publication should be used for this specific type of side effect (immune-related colitis).
Patients who receive checkpoint inhibitors experience immune-related side effects that require immune suppression to manage. This is different from the management of diarrhea caused by other treatments for cancer. Nurses need to be aware of this specific cause of similar symptoms and be knowledgeable about its management.
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.)