Ishido, K., Higuchi, K., Azuma, M., Sasaki, T., Tanabe, S., Katada, C., ... & Koizumi, W. (2016). Aprepitant, granisetron, and dexamethasone versus palonosetron and dexamethasone for prophylaxis of cisplatin-induced nausea and vomiting in patients with upper gastrointestinal cancer: A randomized crossover phase II trial (KDOG 1002). Anti-Cancer Drugs, 27, 884–890.

To gain evidence regarding which regimen should be used for the management of highly emetogenic chemotherapy (HEC) induced chemotherapy-induced nausea and vomiting (CINV)

Patients were randomly assigned to the order of receiving either palonosteron and dexamethasone (PD) or aprepitant, granisetron, and dexamethasone (AGD) prophylaxis. The PD regimen was 0.75 mg palonosetron and 13.2 mg dexamethasone IV prior to treatment and 8 mg oral dexamethasone 24 and 48 hours later. The AGD regimen was 125 mg oral aprepitant and 3 mg granisetron and 6.6 mg dexamethasone IV before treatment, followed by 80 mg aprepitant and 4 mg dexamethasone at 24 and 48 hours. During the second cycle, patients were crossed over to the alternative regimen. During cycle 1, CINV and the use of rescue antiemetics were evaluated. After crossover, patients were asked which treatment was more effective and preferred. Rescue medications were metoclopramide or prochlorperazine.

• N = 84   
• MEDIAN AGE = 64.5 years
• AGE RANGE = 30–77 years
• MALES: 79.8%, FEMALES: 20.2%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Most patients had stage IV disease
• OTHER KEY SAMPLE CHARACTERISTICS: All patients were chemotherapy naïve and were scheduled to receive two or more cycles of chemotherapy including cisplatin at 60 mg/m² or more.

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

• PHASE OF CARE: Active antitumor treatment

• Randomized crossover trial

• Common Terminology Criteria for Adverse Events (CTCAE)
• Functional Living Index-Emesis (FLIE) questionnaire
• Complete response rate for acute, delayed, and overall phases defined as no emesis and no use of rescue medications

No significant differences existed between treatment regimens for complete response in the acute phase. The complete response (CR) rate was higher in the delayed (p = 0.025) and overall phases (p = 0.025) in the regimen including aprepitant. Less than 40% with either treatment had no nausea. FLIE scores indicating impact on daily life showed that more patients in the aprepitant-based regimen group were not affected by nausea (p = 0.014). Forty-one percent indicated preference for AGD, 19.7% preferred PD, and 39.3% indicated no preference.

Findings suggest that a CINV prophylactic regimen containing an NK1—in this case, aprepitant—was more effective in preventing CINV than a regimen of palonosetron and dexamethasone alone.

• Data collection methods for response rates were not reported.

Findings support the use of a triple drug regimen of a 5HT3, NK1, and dexamethasone for patients receiving HEC. Nausea in the delayed phase continues to be an ongoing problem that is not completely relieved with these regimens. Further research is needed to identify other adjuvant medications to address nausea.