Palonosetron Reduces Postoperative Nausea and Vomiting: Presented at ASA

To print: Select File and then Print from your browser's menu
---------------------------------------------------------------------------------------
Title: Palonosetron Reduces Postoperative Nausea and Vomiting: Presented at ASA
URL: http://www.pslgroup.com/dg/231556.htm
Doctor's Guide
October 24, 2008

By Deborah Brauser

ORLANDO, Fla -- October 24, 2008 -- Palonosetron, a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, has been found to reduce postoperative nausea and vomiting (PONV), according to combined findings from 2 phase 3 trials presented here at the American Society of Anesthesiologists (ASA) 2008 Annual Meeting.

Lead investigator of the combined analysis Keith Candiotti, MD, University of Miami Health System and Miller School of Medicine, Miami, Florida, reported the results here on October 20. The study was designed to investigate the efficacy and safety of 3 doses of palonosetron versus placebo for the prevention of PONV in both an outpatient setting and an inpatient setting.

In the first trial, 547 patients undergoing outpatient abdominal or gynaecological laparoscopic surgery were enrolled in centres in the United States. In the second study, 544 predominantly female patients undergoing inpatient gynaecologic or breast surgery were enrolled in European centres.

All patients in both trials received general anaesthesia followed by either a 0.025, 0.05, or 0.075-mg dose of intravenous palonosetron prior to anaesthesia induction. Subjects were then assessed for 3 days post-surgery. The primary efficacy endpoint was complete response (defined as no emetic episode and no use of rescue medications) at the 0- to 24-hour and 24- to 72-hour intervals.

Secondary endpoints included time to treatment failure (defined as either time to first emetic episode or time to first administration of rescue medication) and severity of nausea (none, mild, moderate, severe).

Additionally, in the outpatient study, the impact of nausea and emesis was measured using a validated 4-point scale of "not at all," "a little bit," "quite a bit," or "very much."

Results at the end of the trial showed that the 0.075-mg dose of palonosetron had the greatest effect across endpoints in both study settings. In the outpatient study, complete response rates for the 0.075-mg dose versus placebo were as follows: 43% versus 26% during the 0- to 24-hour interval (P = .004); 49% versus 41% during the 24- to 72-hour interval (P = .188); and 39% versus 24% during the 0- to 72-hour interval (P = .010).

For the inpatient study, complete response rates for the 0.075-mg dose of palonosetron versus placebo were as follows: 56% versus 36% during the 0- to 24-hour interval (P = .001); 70% versus 52% for the 24- to 72-hour interval (P = .002); and 52% versus 36% during the 0- to 72-hour interval (P = .010).

In both the outpatient and inpatient studies, palonosetron significantly delayed the time to treatment failure (P = .024 and P = .004, respectively) and reduced the severity of nausea over the 3-day period (P = .040 and P < .001, respectively).

The treatment effect of the study drug in the outpatient subjects was also associated with less interference in postoperative functioning.

There were no statistical differences in adverse events reported, all of which were consistent with those expected for the 5-HT3 class, with no significant QTc-interval issues.

Said Dr. Candiotti, "5-HT3s are classically believed to not be very good for nausea, but palonosetron appears to reduce its severity. That is an effect that has not been reported with other 5-HT3s, and I think [it is] the most notable finding in these studies."

"The drug has a longer half-life than any of the other 5-HT3s that we're currently using," Dr. Candiotti continued, "and I think it works well; however, it has not been compared against an active comparator and has not been evaluated for rescue. So these are other options that we may utilise [in the future.]"

When asked to summarise the study's findings, Dr. Candiotti noted, "This drug … probably will be beneficial in the anaesthetic management of patients, possibly better in ambulatory patients -- although it appears to have overall increased efficacy in inpatients. But that may be true for all 5-HT3s."

"I think we just have to wait and see how it pans out for other applications and clinical practice," he concluded.

Funding for this study was provided by MGI/Eisai.

[Presentation title: Efficacy and Safety of Palonosetron for the Prevention of Post-Operative Nausea and Vomiting (PONV). Abstract A-1198]

http://www.docguide.com

Return to News Story Page

webmaster@pslgroup.com