Nishimura, J., Satoh, T., Fukunaga, M., Takemoto, H., Nakata, K., Ide, Y., . . . Multi-center Clinical Study Group of Osaka, Colorectal Cancer Treatment Group (MCSGO). (2015). Combination antiemetic therapy with aprepitant/fosaprepitant in patients with colorectal cancer receiving oxaliplatin-based chemotherapy (SENRI trial): A multicentre, randomised, controlled phase 3 trial. European Journal of Cancer, 51, 1274–1282. 

DOI Link

Study Purpose

To evaluate the efficacy of aprepitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) for in patients with colorectal cancer receiving oxaliplatin

Intervention Characteristics/Basic Study Process

CYCLE 1
Patients in the aprepitant group received:
Day 1: 125 mg PO aprepitant, 5-HT3 receptor antagonist IV, 6.6 mg dexamethasone
Days 2 and 3: 80 mg PO aprepitant, 2 mg dexamethasone BID
 
Patients in the fosaprepitant group received:
Day 1: 150 mg fosaprepitant IV, 5-HT3 receptor antagonist, 6.6 mg dexamethasone
Day 2: 2 mg PO dexamethasone BID
Day 3: 4 mg PO dexamethasone BID
 
Patients in the control group received:
Day 1: 5-HT3 receptor antagonist IV, 9.9 mg dexamethasone
 
 
CYCLE 2
All patients were in the aprepitant or fosaprepitant groups

Sample Characteristics

  • N = 413 for full analysis set; however, because of either refusal of chemotherapy (10 patients) or ineligibility on review, only 370 patients were evaluated for the first cycle protocol set. The number lowered further to 338 for second cycle protocol set because of deletion of oxaliplatin from the chemotherapy regimen or lack of data (i.e., not recording in the patient diary).  
  • MEAN AGE = 64.2 years
  • MALES: 61%, FEMALES: 39%
  • CURRENT TREATMENT: Chemotherapy
  • KEY DISEASE CHARACTERISTICS: Colorectal cancer
  • OTHER KEY SAMPLE CHARACTERISTICS: Oxaliplatin-based chemotherapy, adults

Setting

  • SITE: Multisite
  • SETTING TYPE: Hospitals
  • LOCATION: Japan

Phase of Care and Clinical Applications

PHASE OF CARE: Active anti-tumor treatment

Study Design

This was a double-blind, randomized, placebo-controlled trial.

Measurement Instruments/Methods

Patients used a diary on days 1–6 to record the use of rescue antiemetics, severity of nausea, and episodes of vomiting. The severity of nausea was recorded on a four-grade scale. Tolerability, or other adverse effects, were monitored through laboratory tests and a physical examination.

Results

Patients in the aprepitant group had significantly higher rates of no vomiting than patients in the control group overall (relative risk [RR] = 1.14, 95% confidence interval [CI] [1.07, 1.23], p < 0.0001). Analyses of the acute and delayed phases also demonstrated significantly higher rates of no vomiting or patients in the aprepitant group when compared to the control group (acute phase: RR = 1.02, 95% CI [1.01, 1.06], p = 0.013; delayed phase: RR = 1.13, 95% CI [1.06, 1.21], p = 0.0003). In the acute phase, no nausea, no significant nausea, complete response, and complete protection were not significantly different in the aprepitant group compared to the control group. In the delayed phase, patients in the aprepitant group had higher percentages of no significant nausea (RR = 1.09, 95% CI [1, 1.1], p = 0.047), complete response (RR = 1.13, 95% CI [1.02, 1.25], p = 0.02), and complete protection (RR = 1.15, 95% CI [1.02, 1.3], p = 0.02).

Conclusions

For patients receiving oxaliplatin for the treatment of colorectal cancer, CINV prophylaxis with aprepitant or fosaprepitant significantly reduced the rate of vomiting in the acute and delayed phases and significantly reduced the rate of nausea in the delayed phase.

Nursing Implications

Aprepritant and fosaprepitant are safe and effective for the prevention of CINV in patients with colorectal cancer who receive oxaliplatin.