Palonosetron in combination with 1-day versus 3-day dexamethasone for prevention of nausea and vomiting following moderately emetogenic chemotherapy: a randomized, multicenter, phase III trial.
OBJECTIVE
A phase III trial assessed the efficacy of palonosetron plus dexamethasone given once in preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV) following a broad range of moderately emetogenic chemotherapy (MEC) regimens.


METHODS
This multicentre, randomized, open-label, non-inferiority trial evaluated two different treatment groups. One group received palonosetron (0.25 mg intravenously) and dexamethasone (8 mg intravenously) before chemotherapy, while the other was administered the same regimen on day 1 followed by dexamethasone 8 mg orally on days 2 and 3. The primary endpoint was complete response (CR; defined as no emetic episodes and no rescue medication) during the overall phase (days 1-5 after chemotherapy initiation). The non-inferiority margin was predefined as a 15% difference between groups in the primary endpoint.


RESULTS
Of 332 chemotherapy-naïve patients included in the intention-to-treat analysis, 65.1% were female, and 35.2% received anthracycline plus cyclophosphamide (AC)-based regimens. Overall CR rates were 67.5% for those administered dexamethasone only on day 1 (n = 166), and 71.1% for those also administered dexamethasone on days 2 and 3 (n = 166; difference -3.6% (95% confidence interval, -13.5 to 6.3)). CR rates were not significantly different between groups during the acute (0-24 h post-chemotherapy; 88.6% versus 84.3%; P = 0.262) and delayed phases (days 2-5; 68.7% versus 77.7%; P = 0.116).


CONCLUSIONS
Palonosetron plus single-dose dexamethasone administered before common MEC regimens provide protection against acute and delayed CINV which is non-inferior to that of palonosetron plus dexamethasone for 3 days. However, the major benefit of the single-day regimen occurs in patients receiving non-AC MEC regimens.
Celio
Luigi
L
Medical Oncology Unit 2, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy. luigi.celio@istitutotumori.mi.it
Frustaci
Sergio
S
Denaro
Angela
A
Buonadonna
Angela
A
Ardizzoia
Antonio
A
Piazza
Elena
E
Fabi
Alessandra
A
Capobianco
Alba Maria
AM
Isa
Luciano
L
Cavanna
Luigi
L
Bertolini
Alessandro
A
Bichisao
Ettore
E
Bajetta
Emilio
E
D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006305:Health Status Indicators; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy*; D000077924:Palonosetron; D011812:Quinuclidines / Q000008:administration & dosage / Q000627:therapeutic use*; D018570:Risk Assessment; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy*
D018943:Anthracyclines; D018931:Antineoplastic Agents, Hormonal; D007546:Isoquinolines; D011812:Quinuclidines; D012702:Serotonin Antagonists; D000077924:Palonosetron; D003907:Dexamethasone