title: A phase II dose-ranging study of palonosetron in Japanese patients receiving moderately emetogenic chemotherapy, including anthracycline and cyclophosphamide-based chemotherapy.
abstract: BACKGROUND
  The 5-HT(3) 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-HT(3) 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.
  
  
  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.
  
  
  CONCLUSIONS
  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).
authors: Department of Medicine and Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Ehime, Japan. ysegawa1174@aol.com
authors: Y
authors: Y
authors: Segawa
authors: K
authors: K
authors: Aogi
authors: K
authors: K
authors: Inoue
authors: M
authors: M
authors: Sano
authors: I
authors: I
authors: Sekine
authors: Y
authors: Y
authors: Tokuda
authors: H
authors: H
authors: Isobe
authors: T
authors: T
authors: Ogura
authors: M
authors: M
authors: Tsuboi
authors: S
authors: S
authors: Atagi
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000009:adverse effects; D000932:Antiemetics / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D044466:Asian People; D003520:Cyclophosphamide / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D000077924:Palonosetron; D011812:Quinuclidines / Q000008:administration & dosage* / Q000009:adverse effects; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D018943:Anthracyclines; D000932:Antiemetics; D007546:Isoquinolines; D011812:Quinuclidines; D000077924:Palonosetron; D003520:Cyclophosphamide