title: Effective cross-over to granisetron after failure to ondansetron, a randomized double blind study in patients failing ondansetron plus dexamethasone during the first 24 hours following highly emetogenic chemotherapy.
abstract: In view of the similarity in chemical structure of the available 5HT(3)-receptor antagonists it is assumed, whilst these agents all act at the same receptor, that failure to one agent would predict subsequent failure to all 5HT(3)-receptor antagonists. We conducted a randomized double blind trial of granisetron 3 mg plus dexamethasone 10 mg versus continued treatment with ondansetron 8 mg plus dexamethasone 10 mg in patients with protection failure on ondansetron 8 mg plus dexamethasone 10 mg during the first 24 hours following highly emetogenic chemotherapy. Of 40 eligible patients, 21 received ondansetron + dexamethasone and 19 received granisetron + dexamethasone. We found a significant benefit from crossing-over to granisetron after failure on ondansetron. Of the 19 patients who crossed over to granisetron, 9 patients obtained complete protection, whereas this was observed in 1 of the 21 patients continuing ondansetron, P = 0.005. These results indicate that there is no complete cross-resistance between 5HT(3)-receptor antagonists, and that patients who have acute protection failure on one 5HT(3)-receptor antagonist should be offered cross-over to another 5HT(3)-receptor antagonist.
authors.affiliation: Rotterdam Cancer Institute and University Hospital Rotterdam, IJsselland Hospital Rotterdam, Albert Schweitzer Hospital Dordrecht, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: de Wit
authors.forename: A C
authors.initials: AC
authors.lastname: de Boer
authors.forename: G H
authors.initials: GH
authors.lastname: vd Linden
authors.forename: G
authors.initials: G
authors.lastname: Stoter
authors.forename: A
authors.initials: A
authors.lastname: Sparreboom
authors.forename: J
authors.initials: J
authors.lastname: Verweij
mesh_terms: D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D018592:Cross-Over Studies; D003907:Dexamethasone / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D017829:Granisetron / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017294:Ondansetron / Q000008:administration & dosage*; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D003907:Dexamethasone; D017829:Granisetron; D017294:Ondansetron