To provide guidance to clinicians for the prevention and management of chemotherapy-induced nausea and vomiting in patients receiving cancer chemotherapy of varying emetogenic potential

The evidence-based process was not fully described. Specific research was not stated. Literature cited were the antiemetic resource center at www.mascc.org and the Antiemetic Subcommittee of the Multinational Association of Supportive Care in Cancer 2004 consensus conference, cited in Annals of Oncology 2006, 17, 20–28.

Levels of evidence and grades of recommendation as used by the American Society of Clinical Oncology (ASCO) were applied to specific recommendations and considered by the authors and European Society for Medical Oncology (ESMO) faculty. This was approved by the ESMO guidelines working group.

This reference provides definitions of nausea and vomiting; relative emetogenic potential of oral and IV drugs; recommended drugs, dosing, and schedules for antiemetic drugs; and recommendations for management of nausea and vomiting based on emetogenic potential.

Specific regimens are outlined below. Stated level (I–V) and grade of evidence assessed are shown in parentheses.

• Acute nausea and vomiting
  • High-emetogenic potential: Serotonin antagonists + corticosteroid + aprepitant (I, A)
  • Anthracycline + cyclophosphamide: Serotonin antagonist + dexamethasone + aprepitant (II, A)
  • Moderate potential: Serotonin antagonist + corticosteroid (I, A)
  • Low potential: Single agent such as corticosteroid (III, IV, D)
  • Minimal potential: No prophylaxis (V, D)

• Delayed nausea and vomiting
  • High-emetogenic potential: Corticosteroid + aprepitant (II, A)
  • Anthracycline +cyclophosphamide: Dexamethasone or aprepitant (II, A)
  • Moderate potential: Corticosteroid (I, A) or serotonin antagonist (II, B)
  • Low potential: No routine prophylaxis
  • Minimal potential: No routine prophylaxis

• Specific issue recommendations
  • Multiple-day chemotherapy: As for acute on chemotherapy days and as delayed 1–2 days after chemotherapy
  • Refractory nausea and vomiting: Consider aprepitant if not already used or add dopamine antagonists to serotonin antagonists and corticosteroids (V, D)
  • Anticipatory nausea and vomiting: Lorazepam or similar drugs, behavioral techniques (V, D)
  • High-dose chemotherapy: Corticosteroids, serotonin and dopamine antagonists in full doses (III, C)

• The principal author performed ad hoc advisory board activity for multiple pharmaceutical companies and was conducting research sponsored by Merck.
• The secondary author was a member of advisory boards on palonosetron and aprepitant, had been a sponsored speaker, and had conducted research on casopitant and fosaprepitant.
• Recommended timing of interventions for delayed nausea and vomiting prophylaxis was unclear.
• The authors were not clear if the recommendation was to use these medications prophylactically interventionally for delayed symptoms.
• No discussion was provided regarding dosage titration approaches to individualize management.

• This guideline provides a good reference for classification of chemotherapeutic agents according to emetogenic potential and a good reference for initial dosing of medications used.
• The recommendations are based on patients who are chemotherapy-naïve.
• The recommendations focus on pharmaceutical management, except for consideration of behavioral techniques for anticipatory nausea and vomiting.

To compare tropisetron plus metopimazine versus tropisetron plus placebo for the prevention of chemotherapy-induced nausea and vomiting (CINV)

This study reported on 82 patients with germ cell tumors scheduled to receive four cycles of cisplatin, given as a five-day treatment every three weeks.

This was a randomized, double-blind trial.

Patients used diaries to record the number of vomiting and retching episodes, nausea severity (on a four-point Likert-type scale), and appetite evaluation (on a four-point Likert-type scale).

Satisfaction with antiemetic treatment was collected via a categorical question (satisfied versus not satisfied). Those who were not satisfied with the antiemetic treatment were withdrawn from the study, as they were requesting additional or other treatments.

Tropisetron plus metopimazine was reported to be superior to tropisetron plus placebo in the overall period (days 1-9) in terms of complete protection from vomiting as well as decreased nausea. The treatment arm also was superior over multiple cycles, providing cumulative emetic protection.

This study addressed an appropriate and effective antiemetic prophylaxis for multiple-day chemotherapy regimens (usually cisplatin-based). However, antiemetic control in both treatment arms was poor.

Since this study was conducted, newer agents (i.e., palonosetron and aprepitant) have been proven to have greater efficacy than the treatments used in this study. Furthermore, the treatments described in this study are known to be inferior to treatments that include a corticosteroid. Finally, the rates of protection from CINV associated with the agents studied are not good.

RESOURCE TYPE: Evidence-based guideline

PHASE OF CARE: Active antitumor treatment

One thousand three hundred and thirty articles were initially retrieved, and a final set of 22 were used for the update.

• Triple drug regimen for prevention of acute CINV—high level of evidence and consensus
• Triple drug regimen with dexamethasone on days 2–4 for non-AC regimens—high level of evidence, moderate consensus
• Triple drug regimen for the prevention of acute CINV with AC-based chemotherapy—high level of evidence and high consensus
• Triple drug regimen with aprepitant or dexamethasone on days 2–3 if fosaprepitant, netupitant, or rolapitant was not used on day 1 to prevent delayed CINV with the AC regimen—moderate level of evidence and moderate consensus
• Olanzapine and 5-HT₃ and dexamethasone can be considered—low evidence and low consensus

Very few studies examining olanzapine were included. More evidence is available.

This review provides guidelines regarding prophylaxis for acute and delayed CINV for patients receiving HEC or AC-based chemotherapy. Recommendations are consistent with those of other professional groups. This review does not include the consideration of dexamethasone-sparing regimens and does not include the full range of olanzapine-based regimen evidence.

PURPOSE: To provide guidance to clinicians for the prevention and management of chemotherapy-induced nausea and vomiting

PATIENT POPULATION: Patients receiving cancer chemotherapy of varying emetogenic potential

PROCESS OF DEVELOPMENT: The process was not fully described. The references cited were the antiemetic resource center on the Multinational Association of Supportive Care in Cancer's (MASCC's) website and the Antiemetic Subcommittee of MASCC's 2004 consensus conference, cited in Annals of Oncology 2006, volume 17, pages 20–28. The levels of evidence and grades of recommendation used by the American Society of Clinical Oncology were applied to specific recommendations and considered by the authors and ESMO faculty.

This reference provides definitions of nausea and vomiting; the relative emetogenic potential of oral and IV drugs; recommendations of drugs, dosing, and schedules for antiemetic drugs; and recommendations for the management of nausea and vomiting based on emetogenic potential.

• The principal author contributed to an ad hoc advisory board activity for multiple pharmaceutical companies and is conducting research sponsored by Merck. The secondary author is a member of an advisory board on palonosetron and aprepitant, has been a sponsored speaker, and conducts research on casopitant and fosaprepitant.
• The recommended timing of interventions for delayed nausea and vomiting prophylaxis is unclear. It is not stated whether the recommendation is to prophylactically use these medications to prevent the problem or to intervene if the delayed symptoms occur.
• There is no discussion of any dosage titration approaches to individualize management.

To evaluate the efficacy of one-day versus three-day administration of aprepitant in combination with palonosetron and dexamethasone for the prevention of acute and delayed nausea and vomiting in patients receiving highly emetogenic chemotherapy (HEC)

• Patients were randomization to three arms.
  • Arm A—A single dose of 0.25 mg palonosetron and 12 mg dexamethasone before receiving HEC and 3-day regimen of aprepitant.
  • Arm B—Aprepitant at 125 mg on day 1 followed by a placebo on days 2 and 3.
  • Arm C—Palonosetron at 0.25 mg 30 minutes before chemotherapy and 18 mg dexamethasone, then placebo resembling aprepitant on days 1–3.
• All patients received 8 mg dexamethasone daily on days 2–4, and all received palonosetron 30 minutes before chemotherapy and aprepitant or placebo 60 minutes before treatment.

• The sample consisted of 75 participants.
• Age: (mean age ± SD)
  • Arm A (n = 29)—59.6 years (SD = 10.7 years)
  • Arm B (n = 30)—58.3 years (SD = 10.5 years)
  • Arm C (n = 16)—56.1 years (SD = 12.6 years)
• The percentage of female patients in arm A was 69%, in arm B was 70%, and in arm C was 87.5%; the percentage of male patients in arm A was 31%, in arm B was 30%, and in arm C was 12.5%. 
• Patients' diagnoses were breast (55%), lung (13%), head and neck (19%), and other (13%).
• The median doses of chemotherapy were similar among groups except for cyclophosphamide. Median dose of cyclophosphamide in arm A was 500 mg/m², in arm B was 600 mg/m², and in arm C was 600 mg/m² (p = 0.04).
• No differences existed between groups in terms of history of motion sickness or pregnancy-induced vomiting.

The study was conducted in a single site.

All patients were in active treatment.

This was a randomized, double-blind, placebo-controlled, comparative pilot study.

• Patients defined nausea on a 100-mm visual analog scale (VAS) ranging from 0 = no nausea to 100 = worst nausea possible.
• Patients documented, via patient diaries, the number of emetic episodes, breakthrough nausea mediation, and nausea severity during the 120-hour observation period after infusion of chemotherapy.

• Initially the study had 3 arms; however, analysis displayed severe emesis with and halted arm C (n = 16).
• Those without emesis during the first 24 hours were similar between arms A and B.
• No significant differences were found in the incidence of overall nausea and severity of nausea.
• During the acute phase, complete response was similar (67% arm A and 70% arm B; p = 0.77).
• In the delayed phase, 63% arm A and 59% arm B (p = 78) had no emesis or use of breakthrough medications.
• A complete response during both phases was observed in 56% of arm A and 52% of arm B (p = 0.78).

This study suggested that a single, 125-mg dose of aprepitant provides similar effectiveness compared to the 3-day regimen. The addition of palonosetron and dexamethasone provided protection against emesis in more than 90% of patients during the 5-day study period.

• Sample size was small with fewer than 100 subjects. 
• The potential for bias was reduced by using study methods.
• No information was provided on how often patients were rating their nausea; patients may have had nausea that was not captured in diaries.

The use of aprepitant has shown to be effective in preventing acute and delayed emesis in patients who are receiving cisplatin- and anthracycline-containing therapies.

To promote the adoption of evidence-based pain practices for older adults with cancer

• Five-month engagement phase—receipt of three relevant clinical practice guidelines for experimental (E) and control (C) groups, pain training and activities for E hospices
• 12-month implementation phase—E group received tools for implementation (e.g., quick reference guides), nurses completed an evidence-based practice (EBP) pain program, sites received a monthly outreach visit from an expert nurse who audited charts for 48 EBP indicators and provided feedback, participation in a monthly teleconference to discuss progress and strategies, sharing on e-sites, weekly pain assessment and management sessions as desired

• N = 16 hospices and 738 patients
• AGE: Hospices see 30 older patients per year; patients were older adults with a mean age of 77.6 years
• MALES: 55.9%, FEMALES: 44.1%
• KEY DISEASE CHARACTERISTICS: End-stage cancer
• OTHER KEY SAMPLE CHARACTERISTICS: 66.3% white

• SITE: Multi-site 
• SETTING TYPE: Home 
• LOCATION: Midwest hospices

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Elder care

• Retrospective, cluster, randomized control trial of 16 hospices
  • Eight in the E group and eight in the C group

• Cancer Pain Practice Index (CPPI), which lists 11 EBP cancer pain practices for older adults
• Mean pain severity
• Medical record abstract tool inclusive of 48 indicators of EBP for pain management
• Numeric Rating Scale 
• Pain severity scale (0–10)
• Verbal Descriptor Scale for pain intensity (mild, moderate, severe)

No significant differences existed between the E and C groups in regards to improvement in the CPPI. A decrease in pain severity was found from baseline to post-intervention in the E group, but this was not statistically significant.

Numerous factors influence a multicomponent intervention. Culture, competing priorities, intervention complexity, and other factors may have a role. Future studies should focus on more specific factors in need of change. Although the patient sample was large, only eight hospices comprised each group for the study.

• Small sample (less than 30)
• Intervention expensive, impractical, or training needs
• Other limitations/explanation: The sensitivity of the CPPI to detect change in provider practice was not established a priori.

Translating research into practice is a primary goal of nursing, and pain guideline translation is essential to improving pain outcomes. Translation, however, takes time and may not translate immediately to improved patient outcomes.

Patients were randomized to receive massage therapy or standard treatment. The massage therapy group received 15 massages that were 3–30 minutes long per week by a trained massage therapist for four weeks. The control group received standard medical care alone.

• N = 34
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Stage I or II breast cancer
• OTHER KEY SAMPLE CHRACTERISTICS: At least three months post-treatment

• Randomized

• Participants were assessed for anxiety.
• Mood scales used three standardized assessment tools: State-Trait Anxiety Inventory (STAI), Profile of Mood States (POMS), and Symptom Checklists-90-R (SCL-90-R).
• Immune and neuroendocrine functions were monitored using blood levels of specific immune system markers.

Massage did show some benefit in patient mood scale assessment tools and immune system function. Specifically, reduced anxiety was found on the STAI after the first and last sessions. Reduced depression was found on the POMS depression score after the first and last sessions and from the first to the last day of the study. The SCL-90-R confirmed a reduction in depression from the first to the last day. Wilcoxon’s matched-pairs signed-ranks tests revealed an increase in dopamine and serotonin levels in the massage group; the control group showed a significant increase in norepinephrine. Natural killer cell cytotoxicity did not attain significance.

• The study only looked at the short-term benefit to patients.
• Long-term effectiveness was not demonstrated.
• Sample size was small; participants had early-stage breast cancer diagnoses.
• Patients were randomized based on a coin toss.

• The intervention was PMR for 30-minute sessions three times per week for five weeks versus massage therapy for five weeks versus a control group.
• State-Trait Anxiety Inventory (STAI) was completed before and after the first and last sessions. Longer-term anxiety effect was examined by comparing pre-first day and pre-last day measures on STAI and by the SCL-90R anxiety subscale administered on the first and last days of intervention.  
• Blood samples were drawn to evaluate immune response (NK cell production, cytotoxicity, and hormone levels).

• N = 3 groups (PMR [n = 20] versus massage therapy [n = 22] versus control [n = 16])

• Experimental study

• STAI 
• SCL

Immediate effects: Analysis of variance on STAI revealed a significant (p < 0.001) group effect on the first day’s change scores, and subsequent Bonferroni t-tests revealed reduced anxiety scores for the massage and PMR groups when compared to the control group. The longer-term effects (SCL-90R subscale) did not differ significantly among the three groups.

• Small sample sizes
• Unclear whether the assignment to the three treatment groups was random, which limits the strength of the study

The purpose of this study was to examine the effect of Cimicifuga racemosa (CR BNO 1055) on hot flashes caused by tamoxifen adjuvant therapy in young premenopausal breast cancer survivors. This treatment presents an off-label use of CR BNO 1055 (also known as black cohosh).

Participants took one tablet twice daily with meals for 60 days. Duration of treatment was five years for tamoxifen, and 12 months for CR BNO 1055. Participants were instructed not to initiate new therapies for hot flashes while participating in the study. Forty-six participants were randomly assigned (1-2) to receive tamoxifen 20 mg per day orally (usual-care group;mean age = 47 years); 90 participants received tamoxifen plus CR BNO 1055 corresponding to 20 mg of herbal drug (intervention group; mean age = 46 years.).

• The study enrolled 136 breast cancer survivors aged 35–52 years who completed treatment with segmental or total mastectomy, radiation therapy and adjuvant chemotherapy.
• Inclusion Criteria: Premenopausal status with regular menstruation and normal duration of cycle, and breast cancer diagnosis with estrogen receptor–positive tumor.
• Exclusion criteria: Refusal to consider a study treatment for relief of symptoms, history of other cancers, and history of serious chronic medical conditions.

This was a two-arm, randomized and open-label trial. The primary endpoint was to assess the effect of CR BNO 1055 on the frequency and intensity of hot flushes.

Control visits occurred every two months, when the supply of CR BNO 1055 was replaced and clinical assessments made. Hot flashes were considered severe when five or more heat episodes occurred during the day and were accompanied by sweating, sleep disturbances, feeling of irritation, and anxiety. A few episodes of heat with discrete sweating were classified as moderate hot flushes. Participants completed hot flash diaries at baseline, at every control visit, and at the end of the study at 12 months.

The hot flash patterns were significantly different between the two groups using Fisher’s exact test (p < 0.01). Among the 46 study participants included into the usual-care group, 73.9% experienced severe hot flushes and 26.1% moderate symptoms. Among the 90 study participants in the intervention group, at the end of the study, 46.7% were free of hot flashes, and 24.4% reported severe symptoms.

In the intervention group, the administration of CR BNO 1055 in combination with tamoxifen for a 12-month period significantly reduced the vasomotor episodes induced by tamoxifen in breast cancer survivors.

Methodologic problems included an open label trial  and unbalanced arms  (twice as many participants in the Black Cohosh group as in the usual care group).

The intervention consisted of 30-minute progressive muscle relaxation (PMR) sessions three times per week for five weeks versus massage therapy for five weeks versus a control group. Participants completed the State-Trait Anxiety Inventory (STAI) before and after the first and last sessions. Longer-term anxiety effect was examined by comparing pre first day and pre last day measures on the STAI and by the Symptom Checklist (SCL)-90R (revised) anxiety subscale administered on the first and last days of intervention. Blood samples were drawn to evaluate immune response for natural killer (NK) cell production, cytotoxicity, and hormone levels.

The study reported on three groups: PMR (n =  20), massage therapy (n = 22), and control (n = 16).

A three-group experimental study design was used.

• STAI
• SCL-90R

ANOVA on STAI revealed a significant (p < 0.001) group effect on the first day’s change scores; subsequent Bonferroni t tests revealed reduced anxiety scores for the massage and PMR groups when compared to the control group. The longer-term effects (SCL-90R subscale) did not differ significantly among the three groups. Massage therapy demonstrated an increase in dopamine, serotonin, NK cells, and lymphocytes.

This study supports the use of massage treatment and relaxation therapy to reduce anxiety, pain, and depression in women with breast cancer.

• The study had small sample sizes.
• It is not clear whether assignment to the three treatment groups was random, which limits the strength of the study.