A randomized double-blind comparison of ondansetron and metoclopramide in the prophylaxis of emesis induced by cyclophosphamide, fluorouracil, and doxorubicin or epirubicin chemotherapy.

Abstract

Seventy-five breast cancer patients scheduled to receive a first course (in a new cycle) of cyclophosphamide, fluorouracil, and doxorubicin (FAC) or epirubicin (FEC) participated in a double-blind crossover study to compare the antiemetic efficacy and safety of ondansetron (GR38032), a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, and metoclopramide. Ondansetron was given as an 8 mg loading dose (4 mg intravenously [IV] plus 4 mg orally) before chemotherapy followed by 8 mg every 8 hours orally for 3 to 5 days. Metoclopramide was given as an 80 mg loading dose (60 mg IV plus 20 mg orally) before chemotherapy followed by 20 mg every 8 hours orally for 3 to 5 days. A "period" interaction in the analysis of emetic response in the first 24 hours necessitated a parallel group analysis of first treatments only, 68 patients being assessable for this parameter. In the first 24 hours, complete or major control (zero to two emetic episodes) of emesis was achieved in 30 of 35 (86%) patients receiving ondansetron and in 14 of 33 (42%) patients receiving metoclopramide (P less than .001). Ondansetron was also more effective in reducing acute nausea. On days 2 to 3, the complete or major responses were significantly better with ondansetron (81% v 65%; P = .033), but there was no statistical difference in the control of nausea. There was a significant patient preference for ondansetron (63% v 26%; P = .001). Extrapyramidal reactions were observed in two metoclopramide treatments; both treatments were otherwise well tolerated. These results are consistent with serotonin (5-HT), being a significant neurotransmitter of cyclophosphamide/doxorubicin- or epirubicin/fluorouracil-induced emesis.

Double-blind, randomized, parallel-group study on the efficacy and safety of oral granisetron and oral ondansetron in the prophylaxis of nausea and vomiting in patients receiving hyperfractionated total body irradiation

“…It is also important to control nausea and vomiting, not only for the immediate nutritional and emotional support of the patient, but also because patients who have had prior exposure to emetogenic chemotherapy may experience anticipatory nausea and vomiting during subsequent treatments. 14,18,[23][24][25] The efficacy of granisetron administered i.v. for prophylaxis of nausea and vomiting induced by highly emetogenic chemotherapy or irradiation has been previously evaluated.…”

“…), have been proven to be more effective than placebo and other active agents in preventing nausea and vomiting induced by highly emetogenic chemotherapy. 11,12,[18][19][20][21] Oral administration of a 5-HT 3 -receptor antagonist such as granisetron or ondansetron not only allows the medication to be absorbed so it can act peripherally and in the central nervous system, but also allows the medication to act locally in the gut to inhibit the emetogenic stimulus. The advantages of oral administration of antiemetic medications are clear: reduced costs compared to i.v.…”

Advances in the Management of Cytotoxic Drug-Induced Nausea and Vomiting

“…Three double-blind studies (7,47,48) have compared ondansetron (8 mg i.v. or an oral loading dose followed by 8 mg orally t.d.s.)…”

Pharmacokinetic profile and clinical efficacy of a once-daily ondansetron suppository in cyclophosphamide-induced emesis: a double blind comparative study with ondansetron tablets

“…The prevention and treatment of these symptoms was greatly improved with the development of selective 5HT3 receptor antagonists, which yield control of nausea and vomiting in more than 70% of patients treated with highly emetogenic chemotherapy during the first cycle of chemotherapy (Kaasa et al, 1990;Bonneterre et al, 1990;Marschner et al, 1991). The 5HT3 receptor antagonist ondansetron is rapidly absorped after oral administration and has an absolute bioavailability of approximately 60%.…”