Annals of Oncology Advance Access published online on June 26, 2009
Annals of Oncology, doi:10.1093/annonc/mdp195
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A phase II study of palonosetron combined with dexamethasone to prevent nausea and vomiting induced by highly emetogenic chemotherapy
1 Department of Respiratory Medicine, Tohoku University Hospital, Sendai
2 Department of Respiratory Medicine, Miyagi Cancer Center, Natori
3 Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa
4 Division of Internal Medicine and Thoracic Oncology, National Cancer Center Hospital, Tokyo
5 Thoracic Oncology Division, National Cancer Center Hospital East, Kashiwa
6 Department of Medicine and Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Ehime
7 Division of Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo
8 Department of Pulmonary Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka
9 Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Hyogo
10 Department of Thoracic Oncology, Aichi Cancer Center, Aichi
11 Department of Thoracic Surgery, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
* Correspondence to: Dr M. Maemondo, Department of Respiratory Medicine, Miyagi Cancer Center, Nodayama 47-1, Medeshima-shiote, Natori 981-1293, Japan. Tel: +81-22-384-3151; Fax: +81-22-381-1174; E-mail: maemondo-ma693{at}pref.miyagi.jp
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.
Materials and 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.
Result: In this study, all patients were given 
50 mg/m2 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.
CINV, emesis, 5-HT3 receptor antagonist, palonosetron
Received for publication September 1, 2008. Revision received February 24, 2009. Accepted for publication March 6, 2009.