Barcelona, Spain—Controlling and minimizing nausea and vomiting enables patients with cancer to continue their chemotherapy. A clinical trial reported at the 2015 European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer shows that the newly approved agent aprepitant (Emend), an oral neurokinin (NK)1 antagonist, improved antiemetic control in patients with colorectal cancer (CRC) who were receiving oxaliplatin-based chemotherapy, according to Junichi Nishimura, MD, Assistant Professor, Osaka University, Japan.
On September 2, 2015, the FDA approved aprepitant in combination with other antiemetic drugs for the prevention of acute and delayed nausea and vomiting associated with chemotherapy. Although recent guidelines have classified the FOLFOX (leucovorin, fluorouracil, and oxaliplatin) and XELOX (capecitabine plus oxaliplatin) therapies as having only moderate emetogenic risk, Dr Nishimura said, the rates of nausea and vomiting in a recent phase 3 study of oxaliplatin-based chemotherapy among patients with metastatic CRC ranged from 60.5% to 73.7%.
Dexamethasone plus a 5-hydroxytryptamine (5-HT3) receptor antagonist is the standard prophylaxis for the prevention of acute emesis.
Dr Nishimura and colleagues conducted the multicenter, randomized, open-label phase 3 SENRI trial to evaluate the usefulness of adding aprepitant in patients with CRC who were receiving oxaliplatin. The investigators enrolled 413 patients with CRC from 25 Japanese centers who were undergoing oxaliplatin-based chemotherapy. The patients were randomized 1:1 to the control group (5-HT3 receptor antagonist plus dexamethasone [Decadron]) or the aprepitant group (5-HT3 receptor antagonist plus dexamethasone and aprepitant or fosaprepitant) in the first course. All patients received aprepitant plus fosaprepitant in the second course.
The primary end point was the percentage of patients with no emesis. The investigators also conducted a sex-based subanalysis, which is of interest, because women experience more chemotherapy-induced emesis than men.
Dr Nishimura reported that significantly more patients in the aprepitant group than in the control group experienced no vomiting overall and in the delayed phase (95.7% vs 83.6%, respectively, and 95.7% vs 84.7%, respectively). The benefit was more pronounced among women receiving aprepitant, with 78% having no nausea and complete protection compared with 64% of women in the control group. Among men, the respective rates were 90% and 81%. No intergroup differences in adverse events were observed.
“In patients with colorectal cancer receiving oxaliplatin-based chemotherapy, the aprepitant therapy during chemotherapy improved antiemetic control compared with the control therapy. The addition of aprepitant might be more effective in female gender,” concluded Dr Nishimura and colleagues.
More Data Needed
Fausto Roila, MD, Director, Medical Oncology Division, Santa Maria Hospital, Terni, Italy, commented that oxaliplatin is an antineoplastic drug that is widely used as an adjuvant treatment for patients with CRC and for many metastatic cancers of the gastrointestinal tract, pancreas, and biliary tract.
An earlier trial of an NK1 antagonist demonstrated a lack of antiemetic effect, so this tempers the extent to which the SENRI findings can be generalized, said Dr Roila. “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,” said Dr Roila.