title: Palonosetron: an evidence-based choice  in prevention of nausea and vomiting induced  by moderately emetogenic chemotherapy.
abstract: OBJECTIVE
  In 2003, the second-generation, 5-HT(3) receptor antagonist (5-HT(3) RA) palonosetron was approved by the FDA for the prevention of nausea and vomiting associated with highly and moderately emetogenic chemotherapy. We reviewed the current knowledge on the role of palonosetron against acute and delayed emesis in patients with solid tumors undergoing single-day moderately emetogenic chemotherapy regimens.
  
  
  METHODS
  A literature review in PubMed was performed to update currently available preclinical and clinical evidence on palonosetron, prioritizing randomized clinical trials.
  
  
  RESULTS
  The distinct pharmacology of palonosetron provides a rationale behind the improved efficacy observed with the drug in prevention of delayed symptoms. This may be explained by allosteric binding properties and by palonosetron-triggered receptor internalization, which result in prolonged inhibition of the 5-HT(3) receptor function. Very recent pharmacology experiments have also suggested that palonosetron would be able to differentially inhibit 5-HT(3)/neurokinin 1 (NK-1) receptor signaling cross-talk. In two recent meta-analyses, palonosetron was shown to be more effective than other available 5-HT(3) RAs in preventing acute and delayed nausea and vomiting for both HEC and MEC. Recent findings also suggest that a single-day regimen of palonosetron plus dexamethasone (both drugs administered intravenously) may provide a reasonable therapeutic alternative to reduce the total dexamethasone dose administered in patients undergoing moderately emetogenic chemotherapy.
  
  
  CONCLUSIONS
  On the basis of accumulating data, the evidence-based international guidelines devised from the major organizations have been recently updated to recommend the use of palonosetron plus 3-day dexamethasone for the optimal prevention of nausea and vomiting due to moderately emetogenic chemotherapy. There is still a need to investigate the efficacy of palonosetron in combination with an NK-1 receptor antagonist and dexamethasone in well-designed randomized trials.
authors: Medical Oncology Unit 1, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. luigi.celio@istitutotumori.mi.it
authors: Luigi
authors: L
authors: Celio
authors: Francesco
authors: F
authors: Agustoni
authors: Isabella
authors: I
authors: Testa
authors: Katia
authors: K
authors: Dotti
authors: Filippo
authors: F
authors: de Braud
mesh_terms: D000932:Antiemetics / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000077608:Aprepitant; D003907:Dexamethasone / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D019317:Evidence-Based Medicine; D006801:Humans; D007262:Infusions, Intravenous; D007391:International Cooperation; D007546:Isoquinolines / Q000494:pharmacology / Q000627:therapeutic use*; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use*; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D064729:Neurokinin-1 Receptor Antagonists; D000077924:Palonosetron; D017410:Practice Guidelines as Topic; D011812:Quinuclidines / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D007546:Isoquinolines; D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D011812:Quinuclidines; D058831:Serotonin 5-HT3 Receptor Antagonists; D000077608:Aprepitant; D000077924:Palonosetron; D003907:Dexamethasone