Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist

Results of a Phase III, single-dose trial versus dolasetron

Authors

  • Peter Eisenberg MD,

    1. California Cancer Care, Greenbrae, California
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    • Dr. Eisenberg has participated in clinical trials and received consulting fees and honoraria from Helsinn Healthcare SA (Lugano, Switzerland), MGI Pharma (Bloomington, Minnesota), GlaxoSmithKline (Research Triangle Park, North Carolina), Merck (Whitehouse Station, New Jersey), Roche (Basel, Switzerland), and Aventis Pharmaceuticals (Bridgewater, New Jersey). Dr. Cartmell is a clinical investigator for MGI Pharma. Dr. Macciocchi is an employee of Helsinn Healthcare SA. Dr. Grunberg is a consultant to Helsinn Healthcare SA and has received honoraria from MGI Pharma.

  • Jazmin Figueroa-Vadillo MD,

    1. Hospital General Mexico, Mexico City, Mexico
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  • Rosalio Zamora MD,

    1. Hospital Regional 1° de Octubre, Mexico City, Mexico
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  • Veena Charu MD,

    1. Pacific Cancer Medical Center, Anaheim, California
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  • Julio Hajdenberg MD,

    1. Pasco-Pinellas Cancer Center, Tarpon Springs, Florida
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  • Alan Cartmell MD,

    1. Comprehensive Blood and Cancer Center, Bakersfield, California
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  • Alberto Macciocchi MD,

    Corresponding author
    1. Helsinn Healthcare SA, Lugano, Switzerland
    • Helsinn Healthcare SA, P.O. Box 357, 6915 Pambio-Noranco (Lugano(, Switzerland
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    • Fax: (011) 41-91-993-21-22

  • Steven Grunberg MD

    1. Fletcher Allen Health Care, Burlington, Vermont
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Abstract

BACKGROUND

Palonosetron, a highly selective and potent 5-HT3 receptor antagonist with a strong binding affinity and a long plasma elimination half-life (approximately 40 hours), has shown efficacy in Phase II trials in preventing chemotherapy-induced nausea and vomiting (CINV) resulting from highly emetogenic chemotherapy. The current Phase III trial evaluated the efficacy and safety of palonosetron in preventing acute and delayed CINV after moderately emetogenic chemotherapy.

METHODS

In the current study, 592 patients were randomized to receive a single, intravenous dose of palonosetron 0.25 mg, palonosetron 0.75 mg, or dolasetron 100 mg, 30 minutes before receiving moderately emetogenic chemotherapy. The primary efficacy endpoint was the proportion of patients with a complete response (CR; defined as no emetic episodes and no rescue medication) during the first 24 hours after chemotherapy. Secondary endpoints included assessment of prevention of delayed emesis (2–5 days postchemotherapy).

RESULTS

In the current study, 569 patients received study medication and were included in the intent-to-treat efficacy analyses. CR rates during the first 24 hours were 63.0% for palonosetron 0.25 mg, 57.1% for palonosetron 0.75 mg, and 52.9% for dolasetron 100 mg. CR rates during the delayed period (24–120 hours after chemotherapy) were superior for palonosetron compared with dolasetron. Adverse events (AEs) were mostly mild to moderate and not related to study medication, with similar incidences among groups. There were no serious drug-related AEs.

CONCLUSIONS

A single dose of palonosetron is as effective as a single dose of dolasetron in preventing acute CINV and superior to dolasetron in preventing delayed CINV after moderately emetogenic chemotherapy, with a comparable safety profile for all treatment groups. Cancer 2003. © 2003 American Cancer Society.

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