Ruhlmann, C.H., Christensen, T.B., Dohn, L.H., Paludan, M., Ronnengart, E., Halekoh, U., . . . Herrstedt, J. (2016). Efficacy and safety of fosaprepitant for the prevention of nausea and emesis during 5 weeks of chemoradiotherapy for cervical cancer (the GAND-emesis study): A multinational, randomised, placebo-controlled, double-blind, phase 3 trial. Lancet Oncology, 17, 509–518. 

To investigate the efficacy and safety of fosaprepitant in combination with palonosetron and dexamethasone in the prevention of nausea and vomiting during five weeks of fractionated radiotherapy and concomitant weekly cisplatin in patients with cervical cancer

Patients received fractionated radiotherapy and concomitant weekly cisplatin 40 mg/m² for five weeks. Patients were randomly assigned to receive either single doses of 150 mg fosaprepitant IV or placebo (saline) in combination with 0.25 mg palonosetron IV and 16 mg dexamethasone orally before cisplatin administration. All patients received 8 mg dexamethasone orally twice a day on day 2, 4 mg twice a day on day 3, and 4 mg once a day on day 4. The treatment was repeated for five weeks. Patients kept daily logs of their symptoms, which were reviewed weekly to determine continued eligibility.

• N = 234   
• MEAN AGE = 47–48 years
• FEMALES: 100%
• CURRENT TREATMENT: Combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Cervical cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Patients who were chemotherapy and radiation therapy naïve, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2, who were able to read, understand, and complete questionnaires and daily records in a patient diary throughout the study period

• SITE: Multi-site   
• SETTING TYPE: Multiple settings    
• LOCATION: Recruited from eight centers in four countries

• PHASE OF CARE: Active antitumor treatment

• Multinational, randomized, double-blind, placebo-controlled, phase-III trial

• Functional Living Index-Emesis (FLIE)
• Common Terminology Criteria for Adverse Events (CTCAE), version 4.02 
• Pearson X2, modified intention to treat approach
• Fine and Gray’s proportional subhazard model (competing risk regression)
• Schoenfeld Residuals Test

Of the patients, 48.7% of the placebo group and 65.7% of the control group with fosaprepitant sustained no emesis at five weeks. A significantly lower cumulative risk of emesis was seen in the fosaprepitant group compared to the placebo group (p + 0.008).

Patients receiving concomitant chemo/radiation therapy for cervical cancer who received fosaprepitant in addition to palonosetron and dexamethasone were less likely to experience emesis and nausea compared to those receiving palonosetron and dexamethasone alone.

Neurokinin 1 receptor antagonists (NK₁s) use should be considered in the prevention of radiation-induced nausea and vomiting.