1572P - Safety and efficacy of oral palonosetron in preventing chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of Moderately Emetogenic...

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Supportive Care
Presenter Daniel Voisin
Authors D. Voisin1, S. Grunberg2
  • 1Helsinn Healthcare, 6915 - Pambio Noranco/CH
  • 2Hematology/oncology Unit, Fletcher Allen Health Care, VT 05401 - Burlington/US

Abstract

Background

Palonosetron (PALO), a pharmacologically distinct 5-HT3 receptor antagonist (RA) offers superior CINV prevention compared with other 5-HT3 RAs when administered as a single IV dose. Oral PALO doses 0.25, 0.50, 0.75 mg were clinically comparable to the approved 0.25 mg IV dose in a pivotal phase 3 single-cycle trial, with 0.50 mg being the FDA/EMA approved dose. A dose of 0.75 mg was selected for the present study to best evaluate safety of oral PALO in multiple cycles of chemotherapy (CT).

Methods

In this multicenter, open-label study, patients received a single 0.75 mg dose of oral PALO (with [at investigator discretion] or without concomitant dexamethasone [DEX]) 60 min prior to MEC (up to a maximum of 4 consecutive cycles). The primary safety and efficacy assessments were adverse event (AE) reporting and the proportion of cycles showing patients complete response (CR: no emesis, no rescue medication) in the acute and delayed intervals.

Results

217 patients (75% female; 61% white, 36% Hispanic; 66% CT-naive) received a total of 654 cycles of MEC (median 3 cycles).The median number of cycles was 3 with ∼ half of patients receiving 4 cycles. Concomitant DEX (8 mg Day 1) was administered in 483 cycles while PALO was given alone in 171 cycles. Generally, antiemetic efficacy was maintained across the CT cycles (Table) with higher CR rates when DEX was given concomitantly vs PALO alone (acute: 74% vs 61%; delayed: 63% vs 60% respectively, all cycles combined).

CR (%)Time Period, hrs Cycle 1(n = 217) Cycle 2(n = 186) Cycle 3(n = 143) Cycle 4(n = 107)
Acute (0-24h) 75 70 72 60
Delayed (24-120h) Overall (0-120h) 63 57 62 58 63 60 60 55

The majority of AEs were mild, with headache the most common related AE in 3.5% cycles PALO alone and 5.4% cycles PALO + DEX. In both the PALO alone and PALO + DEX groups, AEs decreased slightly from cycle 1 to 3 and remained about the same for cycle 4. There were few severe or serious AEs and the profile raised no safety concerns.

Conclusion

Oral PALO was well tolerated and effective in preventing CINV over multiple cycles in patients receiving MEC.

Disclosure

D. Voisin: Yes. Daniel Voisin is a Helsinn employee,

S. Grunberg: Yes Steven Grunberg is an Helsinn Helathcare consultant.