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.

The intervention was five weeks of massage therapy sessions for 30 minutes per session. Massages were given three times per week, for a total of 15 massages (control group).

• The sample had 34 participants.
• Both groups were comprised of women who had received surgery for breast cancer.
• The women had stage I or II breast cancer, diagnosed within the past three years, and were at least three months post any treatment.

A longitudinal randomized controlled trial design was used.

• State-Trait Anxiety Inventory (STAI) 
• Profile of Mood States (POMS)
• Symptom Checklist–90–Revised (SCL-90-R)
• Natural killer cell numbers and assays (blood) measured immediate- and long-term effects.

Anxiety was reduced in the massage group on STAI (p < 0.05) after the first and last sessions (decreased by 25%).

• Random assignment by flip of coin could have introduced bias; a random-number table could have been used to avoid this bias.
• The study had a small sample.

The purpose of the study was to compare the effectiveness of prophylactic G-CSF or GM-CSF with prophylactic antibiotics for the prevention of febrile neutropenia, severe infection, infection-related mortality, and overall mortality in patients of all ages with any type of malignancy receiving myeloablative chemotherapy.

The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE databases were searched from January 1985 to January 2008, as were proceedings from the American Society of Clinical Oncology and the American Society of Hematology (2000–2007). In addition, references from identified trials, relevant reviews, guidelines, and ongoing clinical trials were searched.

Key words included  granulocyte–colony-stimulate factors (G-CSF), granulocyte macrophage–colony-stimulating factors(GM-CSF), antibiotics, cancer

Studies were included if they were randomized, controlled trials conducted from January 1980 to January 2008 comparing G-CSF or GM-CSF prophylaxis with antibiotic prophylaxis in patients with cancer receiving myeloablative chemotherapy.

Studies were excluded if they were non-randomixed and were quasi-randomized with information on perioperative infection prophylaxis, stem cell mobilization, and priming of malignant cells with G-CSF or GM-CSF.

10,924 abstracts and 473 full-text articles were reviewed.

Forty-four were considered for the review.

Two articles were included in the final review.

Subgroup analyses conducted for types of underlying malignancies, baseline risk factors for febrile neutropenia for infection, inpatient versus outpatient setting, type of treatment (chemotherapy, hematopoietic stem cell transplantation), types of growth factors administered, age, and antimycotic prophylactic administration.

It was not possible to conduct a meta-analysis as planned due to differences in outcomes among the two studies included in this review.

Studies that were excluded were made up of 36 trials that compared antibiotics and G-CSF prophylaxis to antibiotic prophylaxis alone, four trials that compared prophylactic antibiotics and growth factors to growth factors prophylaxis alone, one due to different chemotherapeutic agents used in each of the study arms, and one non-randomized study comparison. Therefore, only two studies fit the exact inclusion criteria.

• 195 randomized patients were included in this review.
• The sample size across studies ranged from 40–155 participants.
• Participants were adults with solid tumors (small cell lung cancer or breast cancer) who received either oral antibiotics (ciprofloxacin and amphotericin B or cotrimoxazole) or subcutaneous injections of G-CSF or GM-CSF.

In the two trials evaluated, both showed efficacy for use of prophylactic colony-stimulating factors (G-CSF or GM-CSF) or antibiotics for decreased risk of infection; however neither colony-stimulating factors or antibiotics proved better than the other in adults with solid tumors who received myeloablative chemotherapy. No differences were found for infection-related mortality, treatment-related or early mortality, febrile neutropenia, the incidence of severe infections, or infectious episodes.

The use of prophylactic treatment with G-CSF, GM-CSF, or antibiotics for the reduction of risk of infections among adults receiving myeloablative chemotherapy for the treatment of small cell lung cancer or breast cancer is effective; however, use of a colony-stimulating factor versus an antibiotic is inconclusive in terms of better efficacy. More trials are warranted to evaluate prophylactic antibiotic versus colony-stimulating factor use for reduced risk of neutropenia, febrile neutropenia, infections, hospitalizations, and survival.

Implications for nursing practice include knowledge of the known literature and lack of information available. Use of a prophylactic treatment (colony-stimulating factor or antibiotic) for infection prevention is warranted.