Evaluate the efficacy of new antiemetic combination (aprepitant, granisetron, and dexamethasone) in gastric cancer patients’ receiving chemotherapy regimen (cisplatin 60 mg/m² and 5-flourouracil analog (S-1) 80 mg/m²) in day 1, aprepitant and dexa on day 2 and 3, and dexa on day 4.

S-1 (80 mg/m²) orally x 2 x 3 weeks of a five-week cycle. Cisplatin 60 mg/m² IV on day 8 of each cycle. Antiemetic regimen: aprepitant 125 mg 1 hour before cisplatin plus dexamethasone 9.9 mg IV plus granisetron 3 mg IV 30 minutes before cisplatin infusion on day 1, oral aprepitant 80 mg x 1 & oral dexamethasone 8 mg bid on days 2 and 3, and oral dexamethasone 8 mg bid on day 4. Observations of the patients done 0-120 hours.

• N = 53   
• AGE: Median = 65 years
• MALES: 90.6%  
• FEMALES: 9.4%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Gastric cancer, chemotherapy naïve, receiving cisplatin and S-1 
• OTHER KEY SAMPLE CHARACTERISTICS: ECOG performance status of 0-2, not experienced ANV 24 hours before chemotherapy, did not received radiotherapy to the abdomen or pelvis before 1 week, no CNS metastasis, with other medical condition that can induce a risk for vomiting

• SITE: Multi-site   
• SETTING TYPE: Inpatient    
• LOCATION: 17 institutions of the digestive disease support organization; Japan

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS: Elder care

Prospective observational non-comparative study

Patient self-report of number and timing of any episodes of vomiting or retching; the degree of nausea using a four-point categorical scale (0, none; 1, mild; 2, moderate; 3, severe, use of rescue therapy (frequency and timing), and change in the amount of diet intake, and completed the Functional Living Index-Emesis (FLIE) questionnaire daily on days 1-5. Safety was assessed by physical examination, toxicity used NCI-CTCAE, version 4.

88.7, 98.1, and 88.7 % achieved complete response (CR) (no emesis, and no rescue antiemetics) in the overall, acute, and delayed phases, respectively. While 67.9, 96.2, and 67.9 % achieved complete protection (CR + no significant nausea). Half of the patients had anorexia, FLIE indicated 79.5% of the patients reported minimal or no impact of CINV on QOL. About half of the patients had some degree of anorexia. 30% of the patients reported decrease volume of diet intake to half and 10% could not consume any food during the delayed phase. Antiemetics therapy was well-tolerated.

Addition of aprepitant to standard antiemetic therapy was effective in patients with gastric cancer undergoing treatment with cisplatin and S-1.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)

CINV incidence with highly emetogenic chemotherapy is a challenge. A combination of a recommended JSCO guidelines of aprepitant, granisetron, and dexamethasone was well tolerated and very effective in preventing CINV for patients with gastric cancer receiving cisplatin.

The purpose of this study was to compare outcomes in patients who received aprepitant, azasetron, and dexamethasone versus patients who received a 5-HT₃ receptor antagonist and dexamethasone.

Thirty-seven women received double combination therapy on cycle 1 and then triple combination therapy on cycle 2. Forty-one women received triple combination therapy on cycles 1 and 2. Eighty-five women only received double combination therapy. Double combination therapy consisted of azasetron 10 mg IV and dexamethasone 20 mg IV prior to chemotherapy on day 1. Triple combination therapy consisted of azasetron 10 mg IV, dexamethasone 8 mg IV and aprepitant 125 mg PO prior to chemotherapy on day 1 and then aprepitant 80 mg PO on days 2 and 3.

• N = 163
• AGE: Not stated
• FEMALES: 100%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Endometrial cancer (n = 62), cervical cancer (n = 27), ovarian cancer (n = 74)

• SITE: Single site 
• SETTING TYPE Not specified 
• LOCATION: Japan

PHASE OF CARE: Active anti-tumor treatment

Prospective, non-randomized trial

Nausea, vomiting, and appetite loss were self-reported and measured on a scale of 0 (not present) to 2 (strongly present). Dietary intake was self-reported and measured on a scale of  0-10 for staple foods and 0-10 for side dishes (score of 20 = perfect score). It is unclear how the investigators collected this data, but it was collected for day 1 and day 5.

For the patients who received double combination therapy on cycle 1 and then triple combination therapy on cycle 2, there was a significant improvement in day 5 (delayed) nausea (p < 0.001), appetite loss (p < 0.0001), and dietary intake (p = 0.04) on cycle 2. There was not a significant difference in vomiting.

When comparing all cycles with double combination therapy to all cycles with triple combination therapy, patients who received double combination therapy for that cycle reported higher nausea (p = 0.002), appetite loss (p = 0.002), and vomiting (p = 0.02) on day 1. There were no significant differences between the two groups on day 5.

This study suggests that triple combination therapy (aprepitant plus dexamethasone plus azasetron) may result in less delayed nausea and less acute nausea, appetite loss, and vomiting, when compared to double combination therapy (dexamethasone plus azasetron). However, there are several limitations to this study.

• Baseline sample/group differences of import–unsure if there are baseline differences
• Risk of bias (no random assignment)
• Measurement/methods not well described
• Measurement validity/reliability questionable

Aprepitant, when added to dexamethasone and azasetron, for patients with gynecological cancers receiving carboplatin and paclitaxel may decrease acute nausea, appetite loss, and vomiting as well as delayed nausea.

The purpose of this study was to evaluate the efficacy of triplet therapy aprepitant, palonosetron, and dexamethasone in patients receiving carboplatin and paclitaxel (CP) for gynecologic malignancy.

Seventy patients with gynecologic cancer receiving CP were enrolled into a prospective single-arm study with APR (125 mg on day 1, 80 mg on days 2–3), PALO (0.75 mg), and DEX (20 mg) before initiating chemotherapy. The primary endpoint was delayed complete response (CR) rate (i.e., no vomiting and no rescue) at 24–120 hours after chemotherapy administration.

• N = 70   
• AGE: Median age = 57 (range = 37-80) 
• FEMALES: 100%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Gynecologic cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Chemotherapy-naïve women aged 20 years or older with a confirmed diagnosis of gynecologic malignancy; scheduled to receive CP; Eastern Cooperative Oncology Group performance status of 0–1 and adequate organ function

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Nara Medical University, Japan

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Elder care

Single-arm phase II

• MASCC Antiemetic Tool was used to evaluate the efficacy of the antiemetic used 
• The primary endpoint was the complete response (CR) rate (no emetic episodes, no rescue medication) in the delayed phase for the first cycle
• The secondary endpoints were CR rates in the acute and overall phases; complete control (CC) rates (no significant nausea, no rescue medication) in the acute, delayed, and overall phases;
• Total control (TC) rates (no emetic episodes, no rescue medication, and no nausea) in the acute, delayed, and overall phases; and adverse events.“Acute” was defined as up to 24 hours after the administration of CP, and “delayed” was defined as the 24–120 hours after administration. 
• No significant nausea was defined as a MASCC Antiemetic Tool score of 3 or lower.

• Seventy patients were enrolled as planned, and all were eligible .
• Delayed CR rate was 97.1% (68/70). CR rates in the acute and overall phases were 100% (70/70) and 97.1% (68/70), respectively. CC rates in the acute, delayed, and overall phases were 98.6% (69/70), 1.4% (64/70), and 91.4% (64/70), respectively. TC rates in the acute, delayed, and overall phases were70% (49/70), 87.1% (61/70), and 65.7% (46/70), respectively.
• Proportions of the incidence of adverse events were 42.5 and 2.5% of constipation grades 1 and 2 (17/40 and 1/40), respectively, and 5% of insomnia grade 1 (2/40). No grade 3 or 4 events were observed.
• In the univariate logistic analysis, there were no significant factors associated with the delayed CR rate.
• Only the factor of age 50 years and younger tended to be associated with a poor delayed CR rate (p = 0.096).

Adding APR to PALO and DEX combination therapy may be promising for patients with gynecologic cancer receiving CP. A phase III study comparing APR, PALO, and DEX to PALO and DEX should be conducted in order to determine if APR in addition to PALO and DEX is efficacious for female patients receiving CP.

• Small sample (< 100)
• Intervention expensive, impractical, or training needs

Encourage more studies to better determine the efficiency of APR in addition to PALO and DEX in this patient population.

STUDY PURPOSE: The primary aim of this systematic review was to compare the efficacy and safety of olanzapine with standard antiemetics.

TYPE OF STUDY: Systematic review/meta-analysis

DATABASES USED: MEDLINE, EMBASE, SCOPUS, Cochran Central Register of Controlled Trials

YEARS INCLUDED: Inception to July 15, 2016

INCLUSION CRITERIA: The studies of interest were those that reported either olanzapine as add-on treatment (dexamethasone plus 5-HT₃ antagonist, with or without NK1 antagonist) or olanzapine monotherapy compared to standard treatment. 

EXCLUSION CRITERIA: Duplicate data and non-English language studies.

TOTAL REFERENCES RETRIEVED: 573

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Two independent reviewers

FINAL NUMBER STUDIES INCLUDED: 16 studies however, only 9 were pooled for statistical analysis because 1 was an observational study, and 6 clinical trials did not have a comparison group. 

TOTAL PATIENTS INCLUDED IN REVIEW 1,308 (in the 9 studies included in analysis) 

SAMPLE RANGE ACROSS STUDIES: 17-380

KEY SAMPLE CHARACTERISTICS: Multiple tumor types, focused on patients receiving olanzapine.

PHASE OF CARE: Active anti-tumor treatment

The results of the combined studies included in the meta-analysis showed that CR (defined as no emesis and no rescue drugs) was achieved more frequently for delayed CINV (RR = 1.77, 95% CI [1.07, 1.49]) and overall CINV (RR = 1.32; 95% CI [1.08, 1.62]). Olanzapine was not superior to traditional antiemetic therapy for acute CINV. The most frequently occurring adverse events were drowsiness and constipation.

• Limited number of studies included
• High heterogeneity
• Multiple measures used to determine the presence of nausea and vomiting.

Nurses caring for patients with delayed CINV can consider the use of olanzapine, but also must recognize the common occurring drowsiness and constipation with the use of the medication.

Evaluate the safety and efficacy of olanzapine for prevention and rescue of CINV

Medical records of adult patients who received one or more doses of olanzapine for prophylaxis of CINV or treatment of breakthrough CINV were reviewed. Routinely patients are phoned by a pharmacist or research assistant 72 hours after each chemotherapy cycle and an assessment of CINV is documented in the electronic record. Patients were on various chemotherapy and antiemetic regimens.

• N: 170   
• AGE: Median = 51 years (range = 20-85)
• MALES: 16.5%  
• FEMALES: 83.5%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Various tumor types–breast was most common (57%)

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Canada

Retrospective descriptive

Olanzapine was used for breakthrough in 154 patients over 193 treatment cycles. 88.1% of patients reported that it improved nausea, and 21.8% reported it improved vomiting. Twenty patients had been given olanzapine for prophylaxis. Among these 100% reported it improved nausea, and 35% said it improved vomiting. Analysis showed that olanzapine effects were not related to cycle, emetogenicity of the chemotherapy, or antiemetic regimen used. Side effects observed were sedation with continuation of olanzapine (29.5%).

Olanzapine was shown to have been effective as a rescue medication for CINV and may be effective for CINV prophylaxis.

• Baseline sample/group differences of import         
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Other limitations/explanation: No subgroup analysis based on emetogenicity of chemotherapy and antiemetic regimen–these factors could confound results seen. No standard approach to measurement or reporting of CINV symptoms.

Olanzapine can be effective as a rescue medication for CINV and as part of a CINV prophylaxis regimen.

The purpose of the study was to compare the combination of aprepitant and decadron versus metoclopramide and decadron for delayed emesis in patients receiving the same combination of aprepiant, palonosetron, and dexamethasone for the prophylaxis of cisplatin-induced acute emesis.

All patients received on day 1 a combination of 0.25 mg of palonosetron administered IV 30 minutes before the beginning of chemotherapy followed by 12 mg of decadron. Aprepitant was orally administered one hour before chemotherapy. Patients were randomized to receive delayed antiemetics with decadron 8 mg once daily day 2 to 4 plus aprepitant 80 mg daily on day 2 and 3, or decadron 8 mg twice daily on days 2 to 4 plus metoclopramide 20 mg four times a day on days 2 to 4. Patients recorded a diary card days 1 to 6 with reports of nausea, vomiting, adverse events and any rescue treatments using FLIE, and nausea intensity on a visual analog scale.

• N: 284   
• AGE: Adult (categorized as less than 50, 50 to 64, and 65 and up.
• MALES: MTC + Dex arm 71.5%, APR + Dex 71.4%  
• FEMALES: MTC + Dex 28.5%, Apr + Dex 28.6%
• CURRENT TREATMENT: Chemotherapy
• OTHER KEY SAMPLE CHARACTERISTICS: Chemotherapy naïve cancer patients scheduled to receive cisplatin containing chemotherapy at doses 50 mg/m² or above

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: Italy

PHASE OF CARE: Active anti-tumor treatment

Multicenter, double-blind, parallel, randomized 1:1 study aimed to evaluate the efficacy of aprepitant versus metoclopramide

Fisher’s exact test was used to compare the two groups with respect to the endpoints expressed by a binary variable, as well as to evaluate the differential safety. FLIE was used for patient diary and symptom reporting, as well as a visual analog scale for nausea.

During days 2 to 5, complete response was similar in both antiemetic prophylaxes (82.5% with M + D, and 80.3% with A + D).

The effectiveness and safety of the two combinations in the treatment of cisplatin induced CINV in the delayed phase are similar. However, they have very different cost profiles. These are important considerations for treatment-related decisions.

• Self reported lack of power
• May not detect small differences

Both aprepitant + decadron and metoclopramide + decadron are effective for delayed emesis for patients receiving cisplatin. Because of the substantial cost difference, consideration should be given to metoclopramide + decadron for delayed nausea.

To investigate the incidence of CINV among chemotherapy naïve patients with breast cancer receiving docetaxel-cyclophosphamide chemotherapy regimen (MEC). To investigate the prophylactic efficacy of aprepitant on CINV for the patients who experienced CINV in their first chemotherapy cycle

Phase 1: involved 212 breast cancer naïve patients receiving TC and detected the incidence of CINV. Antiemetic therapy on the first cycle consisted of dexamethasone 8 mg (x 3) for day 1 and then dexamethasone 8 mg (x 2) on days 2 and 3 plus 5-hydroxytryptamine (5-HT₃) antagonists (gransetron 1 mg [x 2], or tropisetron 5 mg [x 1]) on day 1. Patient also received 8 mg dexamethasone on day 0. 

Phase 2: for the patient who experienced vomiting and requested rescue antiemetic in the first 120 hours were involved during their second chemotherapy cycle. Patients received same antiemetic regimen prescribed in cycle 1 in addition to aprepitatnt 125 mg orally (x 1) on day 1, and aprepitant 80 mg and dexamethasone 4 mg (x 2) in days 2 and 3 Patients’ diaries and Functional Living Index Emesis (FLIE) questionnaires were collected in cycles 1 and 2.

• N = 185 patient in the observational phase; 32 patient in the efficacy phase (24 evaluable)  
• AGE: Median = 57 years (range = 34-82)
• FEMALES: 100%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Stage I to III breast cancer, chemotherapy naive patients, receiving T-75 mg/m² and C-600 mg/m²
• OTHER KEY SAMPLE CHARACTERISTICS: No anticipatory nausea and vomiting, no radiotherapy, no receiving systemic cortisone, had Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1; and had a life expectancy ≥ 4 months and adequate bone marrow, liver, and renal functions

• SITE: Multi-site   
• SETTING TYPE: Multiple settings    
• LOCATION: 12 sites in Spain

PHASE OF CARE: Active anti-tumor treatment

Open-label, non-comparative, observational clinical trial

FLIE questionnaire on day 1 before chemotherapy and day 6. Patient diary for nausea and vomiting episodes and severity (VAS) and need of rescue antiemetics day 1-6.

On cycle 1, 87% achieved a complete response (no vomiting and no rescue antiemetic). On cycle 2, 23 patients reached a CR (52.2%). The absence of CR significant affected the patients QOL on cycle 1 (p = 0.0124) and 2 (p = 0.0059). No AEs related to aprepitant were observed in cycle 2.

Antiemetic guidelines of dexamethasone for 3 d plus 5-hydroxytryptamine (5-HT₃) antagonists on day 1 is associated with low incidence of CINV for patient receiving MEC. Aprepitant is effective as a secondary treatment line for patients who do not response to the first-line antiemetic.

• Small sample (< 30)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)

Even with the use of standard antiemetics (steroid, %HT3 RAs) with patient receiving MEC, some patients still experience CINV. Failing to be free of nausea and vomiting negatively affect patients’ quality of life and therefore required additional therapy (aprepitant).

The purpose was to evaluate the efficacy of a three-day aprepitant regimen to manage CINV during cycle one of moderately emetogenic chemotherapy.

Three-day regimen of aprepitant plus ondansetron and dexamethasone compared to three-day regimen of placebo plus ondansetron and dexamethasone.

• N = 480   
• AGE: Overall mean = 60.3, range = 23-85 years 
• MALES: 55%
• FEMALES: 45%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Any cancer type
• OTHER KEY SAMPLE CHARACTERISTICS: Receiving cycle one of non-anthracycline plus cyclophosphamide (AC)-based moderately emetogenic chemotherapy (MEC), aged 20 years and older, Eastern Cooperative Oncology Group (ECOG) performance status 0–2 or Karnofsky score of 60 or greater, predicted life expectancy of 4 months or greater. 

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: Korea

PHASE OF CARE: Active anti-tumor treatment

Randomized, controlled trial, double-blind.

Measures of nausea and vomiting were not specifically described but aspects measured were vomiting during the overall phase (0-120 hours), use of rescue therapy during the overall phase, time to first vomiting event during the overall phase, vomiting during the acute (0–24 hours following initiation of chemotherapy) and delayed (25–120 hours following initiation of chemotherapy) phases.

Participants who received the three-day aprepitant regimen did not have statistically significant fewer episode of vomiting or use of rescue medications in the overall phase (0-120 hours after chemotherapy) as compared with those who received the placebo regimen.

The addition of aprepitant to a standard antiemetic regimen for moderately emetogenic chemotherapy did not result in significant improvement in CINV.

Measurement/methods not well described

For patients receiving moderately emetogenic chemotherapy, adding aprepitant to antiemetic therapy may not provide additional prevention of CINV.

STUDY PURPOSE: Define whether the addition of NK1Ras provides a clinically meaningful benefit for the prevention of nausea and vomiting in patients receiving moderately emetogenic chemotherapy

TYPE OF STUDY: Meta analysis and systematic review

DATABASES USED: MEDLINE (via Pubmed and Ovid) Central databases 

YEARS INCLUDED: January 1990 to October 2016.

INCLUSION CRITERIA: English language, randomized trials evaluating efficacy of NK1 for prevention of CINV in MEC

EXCLUSION CRITERIA: MEC multiple days, combine MEC and HEC, AC based, reviews with pooled analysis, design, retrospective, no randomization.

TOTAL REFERENCES RETRIEVED: 626 

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Initial evaluation done by one member of team, but two others then reviewed the results, and agreement was reached using consensus.

FINAL NUMBER STUDIES INCLUDED: 16 per literature, 15 evaluated in table.

TOTAL PATIENTS INCLUDED IN REVIEW: 3,848

SAMPLE RANGE ACROSS STUDIES: 23-707

KEY SAMPLE CHARACTERISTICS: Studies evaluating the efficacy of NK-1 in chemotherapy with moderately emetogenic chemotherapy, multiple types of cancer, lung, gynecologic, colorectal, and head and neck cancers

PHASE OF CARE: Active anti-tumor treatment     

APPLICATIONS: Elder care, palliative care

Overall, a total of 626 published articles or abstracts were pulled for this systemic review. Based on the inclusion and exclusion criteria, the final review included 13 trials and three abstracts. Only two trials evaluated use of NK-1 in pure MEC regimens. The authors categorized trials as pure MEC (excluding regimens with carboplatin or oxaliplatin), regimens containing carboplatin, and regimens containing oxaliplatin. In the pure MEC group, the addition of an NK-1-RA significantly improved CINV complete response (p = 0.02). In the carboplatin group, the addition of an NK-1-RA significantly improved CINV complete response (p < 0.001). In the oxaliplatin group, the addition of an NK-1-RA did not significantly improved CINV complete response (p = 0.17).

The authors discuss that the addition of NK-1 does improve CINV in carboplatin regimens with moderate emetogenicity, but the benefit is not clear for other moderately emetogenic chemotherapy regimens. This use of NK-1 in moderately emetogenic chemotherapy is not reported in guidelines, but there is still a need to answer the question of benefit in this patient population. With carboplatin, there was evidence of usefulness in patients receiving carboplatin with doses at AUC 4 and above. In mixed regimens, it is difficult as emetogenicity ranges from 30%-90%. Only two trials were evaluated in oxaliplatin containing regimens.

• High heterogeneity

Consideration of adding NK-1 in carboplatin containing regimens is supported by results. Ongoing research is needed to further define patients who would benefit from NK-1 medications.