Dose finding study of granisetron in patients receiving high-dose cisplatin chemotherapy

Abstract

Summary The efficacy and safety of three different doses of granisetron (2pjgkg-', group A; 10;Lgkg-', group B; 40jiygkg-', group C) were compared in a randomised, double-blind study of 157 patients due to receive high-dose cisplatin therapy (mean dose >97 mg m-2). In each group, up to two 3 mg rescue doses of granisetron were allowed if more than mild nausea or vomiting occurred. In group A 30.8%, in group B 61.5% and in group C 67.9% of patients were complete responders (i.e. no vomiting or nothing worse than mild nausea) during the first 24 h. These differences are significant between groups A and B, and A and C. There were no statistically significant differences in any efficacy variable between the 10 g kg-' and 40 jig kg-groups, although in each case the trend favoured the higher dose. Additional rescue doses resulted in resolved or improved symptoms in 95.3% for the first rescue dose and 93.3% for the second. Over the 7 days of the study, 82.7%, 82.7% and 86.8% of patients in groups A, B and C respectively were treated with granisetron alone. Headache was the most common side-effect, reported by 9.6% of patients; the majority of headaches were mild. There was no difference between the treatment groups regarding the adverse event rate. We concluded that prophylactic doses of 10 or 40 jig kg-' lead to a safe and satisfactory degree of control of nausea and vomiting induced by high-dose cisplatin.

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.…”

Prospective evaluation of antiemetic outcome following high-dose chemotherapy with hematopoietic stem cell support

“…[10][11][12][13] The combination of a 5-HT3 receptor antagonist and a corticosteroid represent the current standard of care in the prevention of emesis with moderate to highly emetogenic chemotherapy. 19 For patients receiving high-dose chemotherapy or chemo/ radiotherapy regimens in association with hematopoietic stem cell support, a number of studies suggest that antiemetic control may be a greater challenge in this setting.…”

“…The use of 5-hydroxytryptamine-3 (5HT3) antagonists, such as dolasetron, granisetron and ondansetron, have contributed significantly to the control of nausea and vomiting in patients receiving moderately and highly emetogenic chemotherapy. [10][11][12][13] The great majority of patients receiving emetogenic chemotherapy at standard doses should achieve complete control of emesis at the present time.A number of patient and treatment-related factors predictive for the development of chemotherapy-induced emesis have been defined. These include age, gender, ethanol consumption history, and the intrinsic emetogenicity of the chemotherapy agents.…”

Influence of the Component Excipients on the Quality and Functionality of a Transdermal Film Formulation

“…The dried formulation films were carefully cut into uniform sizes to contain a theoretical equivalent of ∼4 mg of the drug per film. This dose of GRN (4 mg per film) was targeted based on the recommended therapeutic doses of GRN for chemotherapy-induced nausea and vomiting (24). Preliminary studies based on film dimensions showed that GRN (9.1% w/w) in the formulations achieved this target dose per film.…”