A phase II study of palonosetron combined with dexamethasone to prevent nausea and vomiting induced by highly emetogenic chemotherapy.
BACKGROUND
This is a randomized, double-blind, dose-ranging study in patients receiving highly emetogenic chemotherapy (HEC) to evaluate the safety, efficacy, and pharmacokinetics of palonosetron, in combination with dexamethasone.


METHODS
We randomized 233 patients to receive palonosetron as a single i.v. bolus dose of 0.075, 0.25, or 0.75 mg before administration of HEC. Dexamethasone (12-16 mg i.v. on day 1, 8 mg i.v. on day 2, and 4-8 mg i.v. on day 3) was administered for prophylactic antiemesis. Pharmacokinetics of palonosetron was analyzed in 24 patients.


RESULTS
In this study, all patients were given > or =50 mg/m(2) cisplatin, which was considered to be HEC. No significant differences in complete response (CR: no emesis and no rescue medication) rates were found in the first 24 h between the 0.075-, 0.25-, and 0.75-mg groups (77.6%, 81.8%, and 79.5%, respectively). In the 120-h period of overall observation, CR rates increased in a dose-dependent manner. In the 0.75-mg group, we observed a significantly longer time to treatment failure than in the 0.075-mg group (median time >120 versus 82.0 h, P = 0.038). Palonosetron was tolerated well and did not show any dose-related increase in adverse effects.


CONCLUSIONS
Palonosetron at doses of 0.25 and 0.75 mg was shown to be effective in preventing chemotherapy-induced nausea and vomiting with high CR rates of patients treated with HEC in Japan. All tested doses of palonosetron were tolerated well.
Maemondo
M
M
Department of Respiratory Medicine, Tohoku University Hospital, Sendai, Japan. maemondo-ma693@pref.miyagi.jp
Masuda
N
N
Sekine
I
I
Kubota
K
K
Segawa
Y
Y
Shibuya
M
M
Imamura
F
F
Katakami
N
N
Hida
T
T
Takeo
S
S
D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000009:adverse effects; D019540:Area Under Curve; D002945:Cisplatin / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D000077924:Palonosetron; D011812:Quinuclidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*; D055815:Young Adult
D000932:Antiemetics; D000970:Antineoplastic Agents; D007546:Isoquinolines; D011812:Quinuclidines; D000077924:Palonosetron; D003907:Dexamethasone; D002945:Cisplatin