Annals of Oncology Advance Access originally published online on July 15, 2009
Annals of Oncology 2009 20(11):1874-1880; doi:10.1093/annonc/mdp243
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supportive care |
A phase II dose-ranging study of palonosetron in Japanese patients receiving moderately emetogenic chemotherapy, including anthracycline and cyclophosphamide-based chemotherapy
1 Department of Medicine and Thoracic Oncology
2 Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center, Ehime
3 Division of Breast Oncology, Saitama Cancer Center, Saitama
4 Department of Surgery, Niigata Cancer Center, Niigata
5 Division of Internal Medicine and Thoracic Oncology, National Cancer Center Hospital, Tokyo
6 Department of Breast and Endocrine Surgery, Tokai University School of Medicine, Kanagawa
7 Department of Respiratory Disease, National Hospital Organization Hokkaido Cancer Center, Hokkaido
8 Division of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Kanagawa
9 Department of Thoracic Surgery and Oncology, Tokyo Medical University, Tokyo
10 Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan
* Correspondence to: Dr Y. Segawa, Department of Respiratory Disease, National Hospital Organization Yamaguchi-Ube Medical Center, 685 Higashi-Kiwa, Ube, Yamaguchi 755-0241, Japan. Tel: +81-836-58-2300; Fax: +81-836-58-5219; E-mail: ysegawa1174{at}aol.com
Background: The 5-HT3 receptor antagonists (RAs) help maintain the standard of care, in various combinations with other agents, for prevention of chemotherapy-induced nausea and vomiting (CINV). Palonosetron is a new generation 5-HT3 RA with indication not only acute but also delayed nausea and vomiting induced by moderately emetogenic chemotherapy (MEC). This study was carried out to determine the optimal dosage of palonosetron in combination with dexamethasone in patients in Japan.
Patients and methods: This study evaluated the efficacy and safety of palonosetron in patients receiving MEC combined with dexamethasone. Patients received single doses of 0.075, 0.25, or 0.75 mg of palonosetron before MEC. Dexamethasone was infused before palonosetron, at 20 mg for the patients receiving paclitaxel (Taxol) and 8 mg for the patients not receiving paclitaxel. The primary end point was complete response (CR: no emetic episodes and no rescue medication) in the acute phase (0–24 h).
Results: In total, 204 patients (88 men, 116 women; 96 with paclitaxel, 108 without paclitaxel) were assessable for efficacy. No dose–response relationship was observed regarding the CR rate in the acute phase. CR rates increased dose dependently for delayed (24–120 h) and overall (0–120 h) phases in patients receiving anthracyclines and cyclophosphamide combination (AC/EC, n = 80); however, the difference in CR rates among doses was not statistically significant. The most commonly reported adverse events related to palonosetron were constipation and headache, confirming the class safety profile.
Conclusion: This study indicates a statistically nonsignificant trend for the dose–response relationship for antiemetic protection in the delayed and overall phases in AC/EC patients (the regimen currently considered to be more emetogenic than MEC).
Key words: chemotherapy-induced nausea and vomiting, 5-HT3 receptor antagonist, palonosetron
Received for publication September 16, 2008. Revision received February 24, 2009. Revision received March 26, 2009. Accepted for publication March 27, 2009.