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 5HT3-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 5HT3-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 5HT3-receptor antagonists, and that patients who have acute protection failure on one 5HT3-receptor antagonist should be offered cross-over to another 5HT3-receptor antagonist. © 2001 Cancer Research Campaign http://www.bjcancer.com

A Comparative Study of Ondansetron and Granisetron in the Prevention of Postoperative Nausea and Vomiting (Ponv) in Day-Care Surgery

“…This was in contrast to the better efficacy of granisetron in the prevention of chemotherapy-induced nausea and vomiting, which was proven in a number of studies like those by Specter JI et al [14] Carmichael et al [15] and De Wit et al [16] So also in our study there was no significant advantage of one 5-HT3 receptor blocker over the other for the prevention of PONV over 24 hours.…”

Chemotherapy-Induced Nausea and Vomiting: The Importance of Acute Antiemetic Control

“…However, patients receiving doses of cisplatin in excess of 50 mg/m 2 had lower complete response rates (25.0%-57.1%) than those receiving other cytostatic agents (59.3%-67.9%). Furthermore, in a small, randomized, double-blind study of patients failing ondansetron plus dexamethasone during the first 24 hours following highly emetogenic chemotherapy, granisetron plus dexamethasone was compared with continued ondansetron treatment [78,79]. Of the 40 eligible patients, significant benefit was achieved by switching patients to granisetron after failure with ondansetron (p = 0.005) (Fig.…”

Granisetron vs ondansetron: is it a question of duration of 5-HT3 receptor blockade?

“…We read with interest the publication by de Wit et al (2001) that there may be effective cross-over to granisetron after failure on ondansetron; both are selective 5-HT 3 receptor antagonists, a class of drugs considered the 'gold-standard' antiemetic agents for the control of emesis in cancer patients undergoing chemo-and radiotherapy. While we support the outcome that granisetron demonstrates superior efficacy to ondansetron, an effect that has been previously reported by Terrey and Aapro (1996), we have some concerns about the study design and the authors' interpretation of the results.…”

“…We recognise that the trial of de Wit et al (2001) involved only a small number of patients (n=40), however, for the study to be a balanced cross-over design, patients should have been selected from a background of failure on both ondansetron and granisetron with previous chemotherapy cycles. Moreover, the authors fail to discuss the possibility of a psychological bias toward the introduction of the 'new' drug.…”

“…Additionally, de Wit et al (2001) state that, 'there are no data to support the use of higher doses of the same 5-HT 3 receptor antagonists in patients failing the recommended dosage,' citing Gandara et al (1998). However, a dose-related response (P50.001) for oral dolasetron has been shown between doses of 25 and 200 mg (complete response rates 60.5 and 76.3% for 100 and 200 mg dolasetron, respectively; Fauser et al, 1996), despite a recommended dosage for the agent of 100 mg.…”