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.