Aprepitant versus metoclopramide, both combined with dexamethasone, for the prevention of cisplatin-induced delayed emesis: a randomized, double-blind study.
BACKGROUND
A combination of aprepitant, a 5-HT3 receptor antagonist (r.a.), and dexamethasone is recommended for the prophylaxis of cisplatin-induced nausea and vomiting in the acute phase, and aprepitant + dexamethasone (A + D) in the delayed phase. The aim of this study was to verify if A + D is superior to metoclopramide plus dexamethasone (M + D) in preventing delayed emesis in cancer patients receiving the same prophylaxis for acute emesis.


METHODS
A randomized double-blind study comparing A + D versus M + D was completed in previously untreated cancer patients. Before chemotherapy, all patients were treated with intravenous palonosetron 0.25 mg and dexamethasone 12 mg, and oral aprepitant 125 mg. On day 2-4, patients randomly received oral dexamethasone 8 mg plus aprepitant 80 mg once daily (days 2-3) or metoclopramide 20 mg four times daily plus dexamethasone 8 mg bid. Primary endpoint was rate of complete response (no vomiting, no rescue treatment) in day 2-5 after chemotherapy.


RESULTS
Due to difficulty in the accrual of patients, 303 of the 480 planned patients were enrolled, 284 were fully evaluable, 147 receiving A + D, 137 M + D. Day 1 results were similar in both arms. On day 2-5, complete response rate was not significantly different (80.3% with A + D versus 82.5% with M + D, P < 0.38, respectively), and all secondary endpoints were also similar (complete protection, total control, no vomiting, no nausea, and score of Functional Living Index-Emesis; P < 0.24). Adverse events incidence was not significantly different between the two treatments.


CONCLUSIONS
In cancer patients submitted to cisplatin-based chemotherapy, receiving the same antiemetic prophylaxis for acute emesis, A + D is not superior to M + D in preventing delayed emesis, and both treatments present similar toxicity.
NCT00869310.
Medical Oncology Division, 'S. Maria' Hospital, Terni. Electronic address: roila.fausto@libero.it.
F
F
Roila
Clinical Governance, ASUR Marche, Ascoli Piceno.
B
B
Ruggeri
Internal Medicine and Public Health, University of L'Aquila, Spinetoli.
E
E
Ballatori
Medical Oncology Division, 'S. Maria' Hospital, Terni.
S
S
Fatigoni
Medical Oncology Division, 'S. Maria' Hospital, Terni.
C
C
Caserta
Medical Oncology, National Cancer Institute, Milano.
L
L
Licitra
Medical Oncology, National Cancer Institute, Milano.
A
A
Mirabile
Medical Oncology II, University Hospital, Cagliari.
M T
MT
Ionta
Medical Oncology II, University Hospital, Cagliari.
B
B
Massidda
Medical Oncology, Piacenza Hospital, Piacenza.
L
L
Cavanna
Medical Oncology, Piacenza Hospital, Piacenza.
M A
MA
Palladino
Medical Oncology, Azienda Ospedaliera di Legnano, Legnano.
A
A
Tocci
Medical Oncology, Azienda Ospedaliera di Legnano, Legnano.
S
S
Fava
Medical Oncology, Santa Croce e Carle Hospital, Cuneo.
I
I
Colantonio
Medical Oncology, ASUR Marche, Ascoli Piceno.
L
L
Angelelli
Medical Oncology, Molinette Hospital, Torino.
L
L
Ciuffreda
Medical Oncology, University Hospital S. Maria della Misericordia, Udine.
G
G
Fasola
Medical Oncology, S. Antonio Abate Hospital, Trapani, Italy.
F
F
Zerilli
D000203:Activities of Daily Living; D061605:Administration, Intravenous; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000077608:Aprepitant; D002945:Cisplatin / Q000009:adverse effects*; D003907:Dexamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage; D007558:Italy; D008297:Male; D008787:Metoclopramide / Q000008:administration & dosage*; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage* / Q000009:adverse effects; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control* / Q000523:psychology; D000077924:Palonosetron; D011788:Quality of Life; D011812:Quinuclidines / Q000008:administration & dosage; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control* / Q000523:psychology; D055815:Young Adult
D000932:Antiemetics; D000970:Antineoplastic Agents; D004338:Drug Combinations; D007546:Isoquinolines; D009025:Morpholines; D011812:Quinuclidines; D000077608:Aprepitant; D000077924:Palonosetron; D003907:Dexamethasone; D008787:Metoclopramide; D002945:Cisplatin
aprepitant; cisplatin; delayed emesis; metoclopramide