title: Management of highly emetogenic chemotherapy.
abstract: OBJECTIVE
  This review updates the clinical data on antiemetic therapy for chemotherapy classified as highly emetogenic.
  
  
  RESULTS
  A meta-analysis demonstrated that palonosetron was superior to other 5-hydroxytryptamine3 (5-HT3) receptor antagonists at least in the absence of aprepitant. Two major guideline groups have reclassified all chemotherapy that contains cyclophosphamide and an anthracycline as 'highly emetogenic'. Although recommended prophylaxis for drugs in that category includes aprepitant, phase II studies with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) and doxorubicin, bleomycin, vincristine and dacarbazine (ABVD) demonstrated that single agent palonosetron alone provided control of emesis over 85% of patients. A randomized phase III trial of olanzapine versus aprepitant found that the control of emesis was similar and nausea was significantly better controlled with olanzapine. Two studies showed that there is no impact of the moderate cytochrome P450 3A4 (CYP3A4) inhibitor aprepitant on the pharmacokinetics of cyclophosphamide. Surveys in the United States and Europe demonstrated that antiemetic prescribing practices often do not adhere to guidelines even for highly emetogenic chemotherapy.
  
  
  CONCLUSIONS
  The major guideline groups recommend a combination of a 5-HT3 receptor antagonist, dexamethasone and aprepitant ('triple therapy') for treatment categorized as highly emetogenic. Recent data suggest that, although classified as highly emetogenic, palonosetron may provide very good control of emesis for CHOP and ABVD. Guidelines have not made firm recommendations for highly emetogenic chemotherapy administered over several days or stem cell transplant preparative regimens due to the lack of published randomized trials. Although well tolerated and effective, many patients receive suboptimal antiemetic therapy that includes aprepitant.
authors.affiliation: Department of Medical Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada. david.warr@uhn.on.ca
authors.forename: David
authors.initials: D
authors.lastname: Warr
mesh_terms: D000932:Antiemetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D006801:Humans; D014839:Vomiting / Q000139:chemically induced* / Q000188:drug therapy / Q000517:prevention & control / Q000628:therapy*
chemical_list: D000932:Antiemetics