title: Comparison of two dosing schedules of palonosetron for the prevention of nausea and vomiting due to interleukin-2-based biochemotherapy.
abstract: BACKGROUND
  Treatment of metastatic melanoma with interleukin-2-based biochemotherapy involves administration of a combination of moderately and highly emetogenic chemotherapies over 5 days. Corticosteroids for the prevention of biochemotherapy-induced nausea and vomiting (CINV) are contraindicated because they cause lysis of LAK cells produced in response to interleukin-2. Palonosetron is a long-acting, highly potent, second-generation serotonin receptor antagonist. The recommended dosing schedule of palonosetron for the control of CINV due to biochemotherapy is not known.
  
  
  METHODS
  In a phase II design, treatment-naïve patients with metastatic melanoma undergoing the first cycle of biochemotherapy were randomized to receive palonosetron 0.25 mg intravenously for CINV prophylaxis on either days 1 and 4 (schedule 1) or days 1, 3, and 5 (schedule 2). All patients received dacarbazine on day 1, cisplatin, vinblastine, and interleukin-2 on days 1-4, and interferon alpha-2b on days 1-5. We evaluated and compared, by palonosetron dosing schedule, the pattern and the severity of CINV during the first 7 days of treatment and the duration of the 21-day cycle as well as the impact on daily function with the Functional Living Index-Emesis.
  
  
  RESULTS
  Thirty patients (median age 53 years) were enrolled. Eighteen (60%) were men. A consistent trend of a better control of both nausea and vomiting favoring schedule 2 was observed during the first 7 days and throughout the cycle. Significantly more patients experienced nausea on any day during the first 7 days on schedule 1 (mean number of episodes 8.1 ± 1.5) than on schedule 2 (mean number of episodes 5.6 ± 2.3, p = 0.028). The impact on daily function was similar between the two groups.
  
  
  CONCLUSIONS
  Both dosing schedules of palonosetron were tolerated well. Alternate day dosing of palonosetron was more effective in controlling CINV in this patient population.
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Rahat
authors.initials: R
authors.lastname: Noor
authors.forename: Agop Y
authors.initials: AY
authors.lastname: Bedikian
authors.forename: Sandy
authors.initials: S
authors.lastname: Mahoney
authors.forename: Roland
authors.initials: R
authors.lastname: Bassett
authors.forename: Kevin
authors.initials: K
authors.lastname: Kim
authors.forename: Nicholas
authors.initials: N
authors.lastname: Papadopoulos
authors.forename: Wen-Jen
authors.initials: WJ
authors.lastname: Hwu
authors.forename: Patrick
authors.initials: P
authors.lastname: Hwu
authors.forename: Jade
authors.initials: J
authors.lastname: Homsi
mesh_terms: D000932:Antiemetics / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000009:adverse effects* / Q000627:therapeutic use; D007546:Isoquinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D000077924:Palonosetron; D011812:Quinuclidines / Q000008:administration & dosage / Q000627:therapeutic use*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D007376:Interleukin-2; D007546:Isoquinolines; D011812:Quinuclidines; D012702:Serotonin Antagonists; D000077924:Palonosetron