The control of acute cisplatin-induced emesis – a comparative study of granisetron and a combination regimen of high-dose metoclopramide and dexamethasone

Abstract

Summary The anti-emetic efficacy and safety of granisetron, a highly selective and potent 5-HT3 receptor antagonist, was compared with that of high-dose metoclopramide plus dexamethasone in 281 patients due to receive single-day cisplatin chemotherapy (,>49 mg m-). In this single-blind, multicentre study, granisetron (40 1tg kg-') was administered as a single prophylactic 5-min infusion. Dexamethasone (12 mg) was administered as a 30-min infusion followed by a loading dose of 3 mg kg-' metoclopramide. A maintenance dose of metoclopramide 4 mg kg-' was then infused over 8 h. A single prophylactic dose of granisetron was as effective as the combination regimen in the prevention of cisplatin-induced emesis. Of 143 granisetron-treated patients, 100 (70%) were complete responders (no vomiting and no or only mild nausea) compared with 93/138 (67%) patients who received the comparator regimen. Twenty-three percent of granisetron-treated patients experienced one of more adverse events compared with 33% of patients in the comparator group. No extrapyramidal reactions were reported in the granisetron group compared with 13 in comparator-treated patients (8%). This difference was significant (P<0.05). The commonest adverse event in the granisetron group, headache (9.8%) described by the majority of patients as mild, was significantly higher than that reported in the comparator group (3% P = 0.02). Granisetron appears to be a safe and effective agent which can be used as a single agent for the prophylaxis of cisplatin-induced emesis. The simplicity of administration, a single 5-min infusion prior to chemotherapy, and the lack of somnolence or extrapyramidal reactions offer clear advantages over the comparator combination regimen.

Effects of cinacalcet on gastrointestinal hormone release in patients with secondary hyperparathyroidism undergoing dialysis

“…Activation of 5-HT 3 serotonin receptors has been implicated in acute emesis in patients receiving chemotherapy, and the use of specific 5-HT 3 -receptor antagonists has been useful in controlling vomiting [18,19]. Our results indicate that plasma levels of serotonin are not significantly modified by the use of cinacalcet.…”

Comparison of granisetron alone and granisetron plus dexamethasone in the prophylaxis of cytotoxic-induced emesis

“…Toxicity was minimal with no significant differences between treatment groups. These results confirm the antiemetic activity of granisetron and show that it has an additive effect in combination with dexamethasone.As single agents the 5HT3 antagonists granisetron (Marty, 1992;Chevallier, 1993) ondansetron (De Mulder, 1990) and tropisetron (De Bruijn, 1992) have been shown to be at least as effective as conventional treatments in controlling the acute nausea and vomiting experienced by patients receiving highly emetogenic chemotherapeutic regimens. Furthermore, they have an improved safety profile.…”

NCCN Guidelines Insights: Antiemesis, Version 2.2017

“…[29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] For the 2017 update, the NCCN panel added recommendations for a new formulation of granisetron-subcutaneous granisetron extended-release injection-in antiemetic regimens for HEC and MEC based on published data and recent FDA approval (see AE-5, AE-6, AE-7, and AE-A 2; pages 886-888 and 890). It is important to note that subcutaneous granisetron extended-release injection is a unique formulation of granisetron using a polymer-based drug delivery system.…”