NK1 Antagonist Shows Promising Results for Emesis Prevention

The addition of the oral neurokinin-1 (NK1) antagonist aprepitant to an oxaliplatin-based chemotherapy regimen effectively reduced nausea and vomiting in patients with colorectal cancer, according to the results of the phase III SENRI trial (Abstract O-0001) presented at the ESMO 17th World Congress on Gastrointestinal Cancer 2015 in Barcelona.

“We found that the three-drug combination antiemetic therapy of aprepitant, a 5-HT3-receptor antagonist and dexamethasone significantly increased the inhibition rate of vomiting and nausea,” lead study author Junichi Nishimura, assistant professor at Osaka University in Japan, said in a prepared statement. “The inhibition rate was especially clear in females. This three-drug combination might be a good antiemetic treatment option for oxaliplatin-based chemotherapy in patients with colorectal cancer.”

According to the study, FOLFOX and XELOX chemotherapy regimens are considered to have a moderate emetogenic risk; however, more recent data has shown rates of nausea ranging from 60% to 74% and vomiting in about half of patients.

In the SENRI trial, researchers evaluated 413 patients with colorectal cancer randomly assigned to a 5-HT3-receptor antagonist plus dexamethasone or to the same regimen plus aprepitant or fosaprepitant. All patients received aprepitant or fosaprepitant in the second course.

The researchers found that 95.7% of patients in the aprepitant group achieved no vomiting overall compared with 83.6% in the control group. This outcome was achieved without any significant difference in adverse events between the two treatment groups.

The researchers also noted that the addition of aprepitant might be more effective in women. In the control group, 64% of women had an overall complete response compared with 81% of men. Among aprepitant patients, 78% of women had an overall complete response compared with 90% of men. In women, rates of nausea and complete protection were significantly higher in the aprepitant group than in the control group.

According to a press release, the only previous randomized trial evaluating the addition of an NK1 antagonist to prevent oxaliplatin emesis found no benefit.

“Unfortunately the two studies gave different results,” said antiemetics expert and ESMO spokesperson Fausto Roila, who is one of the chairs of the Multinational Association of Supportive Care in Cancer (MASCC) and ESMO Antiemetic Guidelines Committee and director of the Medical Oncology Division, Santa Maria Hospital in Terni, Italy. “My opinion is that because we have contrasting results we need to await new data from other studies before we can conclude whether or not NK1 antagonists can be added to a 5-HT3-receptor antagonist plus dexamethasone in patients treated with oxaliplatin-based chemotherapy.”