Combination antiemetic therapy with aprepitant/fosaprepitant in patients with colorectal cancer receiving oxaliplatin-based chemotherapy (SENRI trial): a multicentre, randomised, controlled phase 3 trial.
BACKGROUND
The oral neurokinin-1 antagonist aprepitant is recommended in several guidelines for preventing chemotherapy-induced nausea & vomiting (CINV) due to highly emetogenic cancer chemotherapy. Little is known about the feasibility and safety of aprepitant in patients treated with oxaliplatin.


METHODS
In this multicentre, open label, randomised, phase 3 trial, we recruited patients with colorectal cancer who underwent an oxaliplatin-based chemotherapy. Patients were centrally randomised in a 1:1 ratio to the control group (5-HT3-receptor antagonist+dexamethasone) or aprepitant group (5-HT3-receptor antagonist+dexamethasone+aprepitant or fosaprepitant) in the first course. All patients were treated with aprepitant/fosaprepitant therapy in the second course. The primary end-point was the proportion of patients with no emesis.


RESULTS
A total of 413 patients entered this clinical trial from 25 centres in Japan. Significantly more patients in the aprepitant group achieved no vomiting overall and delayed phase than those in the control group (95.7% versus 83.6%, and 95.7% versus 84.7%, respectively). The aprepitant group also had statistically significantly higher percentages of no significant nausea, complete response and complete protection than the control group overall. In the control group, the percentages of no vomiting were higher in the second cycle than in the first cycle. The incidence of vomiting occurred day 7 or later was significantly higher in the control group compared with the aprepitant group. Other adverse events were not significant between the groups.


CONCLUSIONS
The aprepitant therapy was more effective than the control therapy for prevention of CINV in colorectal cancer patients receiving an oxaliplatin-based regimen.
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka, Japan. Electronic address: jnishimura@gesurg.med.osaka-u.ac.jp.
Junichi
J
Nishimura
Department of Frontier-Science for Cancer and Chemotherapy, Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka, Japan.
Taroh
T
Satoh
Department of Surgery, Sakai City Hospital, Sakai-Ward Minami Yasui-cho 1-1-1, Sakai, Osaka, Japan.
Mutsumi
M
Fukunaga
Department of Surgery, Sakai City Hospital, Sakai-Ward Minami Yasui-cho 1-1-1, Sakai, Osaka, Japan.
Hiroyoshi
H
Takemoto
Department of Surgery, Sakai City Hospital, Sakai-Ward Minami Yasui-cho 1-1-1, Sakai, Osaka, Japan.
Ken
K
Nakata
Department of Surgery, Yao Municipal Hospital, Ryugecho 1-3-1, Yao, Osaka, Japan.
Yoshihito
Y
Ide
Department of Surgery, Ikeda Municipal Hospital, Jyounan 3-1-18, Ikeda, Osaka, Japan.
Takayuki
T
Fukuzaki
Department of Frontier-Science for Cancer and Chemotherapy, Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka, Japan.
Toshihiro
T
Kudo
Department of Surgery, Minoh City Hospital, Kayano 5-7-1, Minoh, Osaka, Japan.
Yasuhiro
Y
Miyake
Department of Surgery, Kaizuka City Hospital, Hori 3-10-20, Kaizuka, Osaka, Japan.
Masayoshi
M
Yasui
Department of Surgery, Toyonaka Municipal Hospital, Shibahara 4-14-1, Toyonaka, Osaka, Japan.
Shunji
S
Morita
Department of Frontier-Science for Cancer and Chemotherapy, Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka, Japan.
Daisuke
D
Sakai
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka, Japan.
Mamoru
M
Uemura
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka, Japan.
Taishi
T
Hata
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka, Japan.
Ichiro
I
Takemasa
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka, Japan.
Tsunekazu
T
Mizushima
Department of Mathematical Health Science, Graduate School of Medicine, Osaka University, Yamadaoka 1-7, Suita, Osaka, Japan.
Yuko
Y
Ohno
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka, Japan.
Hirofumi
H
Yamamoto
Department of Surgery, National Hospital Organization, Osaka National Hospital, Hoenzakka 2-1-14, Osaka, Osaka, Japan.
Mitsugu
M
Sekimoto
Department of Surgery, Nishinomiya Municipal Hospital, Hayashidacho 8-24, Nishinomiya, Hyogo, Japan.
Riichiro
R
Nezu
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka, Japan.
Yuichiro
Y
Doki
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka, Japan.
Masaki
M
Mori
D000932:Antiemetics / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000077608:Aprepitant; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000009:adverse effects / Q000627:therapeutic use*; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D010071:Oxaloacetates; D014839:Vomiting / Q000517:prevention & control*
D000932:Antiemetics; D009025:Morpholines; D009944:Organoplatinum Compounds; D010071:Oxaloacetates; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000077608:Aprepitant; D000069287:Capecitabine; C579707:fosaprepitant; D002955:Leucovorin; D005472:Fluorouracil
Antiemetics; Aprepitant; Moderately emetogenic chemotherapy; Oxaliplatin