Palonosetron plus 3-day aprepitant and dexamethasone to prevent nausea and vomiting in patients receiving highly emetogenic chemotherapy.
BACKGROUND
The combination of a neurokinin-1 receptor antagonist, dexamethasone, and a 5-HT(3) receptor antagonist is currently the standard antiemetic treatment in patients receiving cisplatin-based high emetogenic chemotherapy (HEC). The aim of this study was to evaluate the efficacy of a combination of palonosetron, a unique second-generation 5-HT(3) receptor antagonist, aprepitant, the only approved neurokinin-1 receptor antagonist, and dexamethasone as antiemetic prophylaxis in patients receiving HEC (cisplatin ≥50 mg/mq).


METHODS
Chemotherapy-naïve adult patients, receiving cisplatin-based HEC, were treated with palonosetron 0.25 mg/i.v., dexamethasone 20 mg/i.v., and aprepitant 125 mg/p.o., 1-h before chemotherapy. Aprepitant 80 mg/p.o. and dexamethasone 4 mg p.o. were administered on days 2-3. Primary end point was complete response (CR; no vomiting and no use of rescue medication), during the overall study period (0-120 h). Secondary end points were complete control (CR and no more than mild nausea), emesis-free rate, and nausea-free rate during the acute (0-24 h), delayed (24-120 h), and overall (0-120 h) periods. Safety was also evaluated.


RESULTS
A total of 222 patients were included in the study. Median age was 62 years, 76.6% were male and 23.4% female, and most common tumors were lung (66.7%) and head and neck (15.8%); 70.3% of patients achieved CR during the overall study period. Complete control, emesis-free rate, and nausea-free rate were 70.3%, 92.8%, and 59.9%, respectively, during the overall phase. The most commonly reported side effects were constipation (39% of patients) and headache (5%).


CONCLUSIONS
This study shows that palonosetron in combination with aprepitant and dexamethasone is effective to prevent chemotherapy-induced nausea and vomiting in patients treated with cisplatin-based HEC.
Longo
Flavia
F
Department of Clinical Oncology A, Sapienza University of Rome, Policlinico Umberto Primo, Rome, Italy. flavia.longo1@gmail.com
Mansueto
Giovanni
G
Lapadula
Vittoria
V
De Sanctis
Rita
R
Quadrini
Silvia
S
Grande
Roberta
R
Gori
Bruno
B
Altavilla
Amelia
A
D'Antoni
I
I
Del Signore
Ester
E
Stumbo
Luciano
L
De Luca
Cristina
C
Cimadon
Barbara
B
Cortesi
Enrico
E
Gamucci
Teresa
T
Di Seri
Marisa
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000932:Antiemetics / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects; D000077608:Aprepitant; D002945:Cisplatin / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006305:Health Status Indicators; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage / Q000627:therapeutic use*; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy*; D000077924:Palonosetron; D011446:Prospective Studies; D011788:Quality of Life / Q000523:psychology; D011812:Quinuclidines / Q000008:administration & dosage / Q000627:therapeutic use*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy*; D055815:Young Adult
D000932:Antiemetics; D000970:Antineoplastic Agents; D007546:Isoquinolines; D009025:Morpholines; D011812:Quinuclidines; D012702:Serotonin Antagonists; D000077608:Aprepitant; D000077924:Palonosetron; D003907:Dexamethasone; D002945:Cisplatin