Efficacy and tolerability of transdermal granisetron for the control of chemotherapy-induced nausea and vomiting associated with moderately and highly emetogenic multi-day chemotherapy: a randomized, double-blind, phase III study

Abstract

Purpose A novel transdermal formulation of granisetron (the granisetron transdermal delivery system (GTDS)) has been developed to deliver granisetron continuously over 7 days. This double-blind, phase III, non-inferiority study compared the efficacy and tolerability of the GTDS to daily oral granisetron for the control of chemotherapy-induced nausea and vomiting (CINV). Patients and methods Six hundred forty-one patients were randomized to oral (2 mg/day, 3-5 days) or transdermal granisetron (one GTDS patch, 7 days), before receiving multi-day chemotherapy. The primary endpoint was complete control of CINV (no vomiting/retching, no more than mild nausea, no rescue medication) from chemotherapy initiation until 24 h after final administration. The prespecified non-inferiority margin was 15%. Results Five hundred eighty-two patients were included in the per protocol analysis. The GTDS displayed noninferiority to oral granisetron: complete control was achieved by 60% of patients in the GTDS group, and 65% in the oral granisetron group (treatment difference, −5%; 95% confidence interval, −13-3). Both treatments were well tolerated, the most common adverse event being constipation.Conclusions The GTDS provides effective, well-tolerated control of CINV associated with moderately or highly emetogenic multi-day chemotherapy. It offers a convenient alternative route for delivering granisetron for up to 7 days that is as effective as oral granisetron.

Antiemetic research: future directions

“…The emergence of gene array technology identifying the genes coding for the 5-HT 3 and NK 1 receptors may allow clinical correlations and more rational selection of antiemetic regimens for patients. For example, patients with genetic variations in the 5-HT 3B receptor gene might respond differently to antiemetic treatment with the 5HT 3 receptor antagonists [46].…”

“…tropisetron) depends on cytochrome P-450 2D6 (CYP2D6) genotype, and rapid and ultrarapid metabolisers could be undertreated [23]. Ultrarapid metabolisers could, however, benefit from treatment with a 5-HT 3 antagonist not dependent of the CYP2D6 enzymes (e.g. granisetron).…”

“…While the intravenous and oral administration of antiemetics is well established, other delivery systems, such as the granisetron trasdermal patches [3] which are available in some countries such as the USA and Australia, may offer more patient choice, can be convenient, reduce pill counts and be particularly useful where compliance to medication is low, where there are swallowing difficulties or where oral absorption may be compromised. Such delivery systems need further research.…”

Granisetron Transdermal System in the Management of Chemotherapy-Induced Nausea and Vomiting

“…28 Information is also available from a pooled population pharmacokinetic analysis, incorporating data from the phase I study (n = 48) and phase II and III studies in cancer patients (n = 793). [28][29][30] Two of these studies are fully published, and the phase II study is available as an abstract. The pharmacokinetics is best described by a two-compartment model with zero-order release from the patch to a buffer compartment and first-order release from the buffer into circulation.…”

“…The efficacy and safety of GTS for CINV were evaluated in two randomized, double-blind, double-dummy, parallelgroup, multicenter, premarketing studies: one was a phase II study (n = 171) for single-day MEC, whose results are available from as an abstract 29 and the other was a pivotal 30 The other was an open-label, cross-over, noninferiority phase IV trial that compared the efficacy of GTS with palonosetron for MEC. 32 The results of all three published studies showed noninferiority of GTS.…”