1573P - The dopamine D2/D3 receptor antagonist APD421 in combination with ondansetron effectively prevents acute cisplatin-induced nausea and vomiting (CINV)

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Supportive Care
Presenter Joern Herrstedt
Authors J. Herrstedt1, Y. Summers2, G. Daugaard3, T.B. Christensen4, K. Holmskov5, P.D. Taylor2, G. Fox6, A. Molassiotis7
  • 1Oncology R, Odense University Hospital, DK-5000 - Odense/DK
  • 2Pulmonary Oncology Unit, University Hospital South Manchester NHS Foundation Trust, Manchester/UK
  • 3Department Of Oncology 5073, Rigshospitalet, Copenhagen University Hospital, DK-2100 - Copenhagen/DK
  • 4Oncology Department Ra65 C8, Herlev Hospital, 2730 - Herlev/DK
  • 5Onkologisk Afdeling R, Odense University Hospital, DK-5000 - Odense/DK
  • 6Clinical Development, Acacia Pharma Ltd, CB22 7GG - Cambridge/UK
  • 7School Of Nursing, Midwifery And Social Work, Manchester University, Manchester/UK

Abstract

Conventional dopamine D2 antagonists are among the oldest antiemetics and are considered to be of only moderate efficacy in CINV. Central dopamine D3 receptors have recently been demonstrated to be involved in the emetic reflex arc, but so far no clinical data have been published for any agents acting at these receptors. In preliminary testing, APD421, a potent D2 and D3-antagonist, showed some single-agent efficacy in preventing vomiting and especially nausea caused by cisplatin. We therefore investigated its efficacy in combination with ondansetron at preventing acute-phase CINV.

Methods

Chemotherapy-naïve patients receiving cisplatin ≥ 50 mg/m2 were given single IV doses of APD421 (20 mg) and ondansetron (8 or 16 mg) 30 minutes prior to the cisplatin. Complete response (CR) was defined as no emetic episodes and no rescue medication in the first 24 h after cisplatin infusion. Prospective nausea scores were measured on a 100 mm visual analogue scale at times 2, 4, 8 and 24 h. After the initial 24 h patients received standard antiemetics.

Results

17 subjects (15M:2F) have taken part so far, receiving a mean cisplatin dose of 71 mg/m2 (range 64-82 mg/m2), of whom 15 have had CR (88%; 95% CI 72-100%). The mean nausea score is 0.7/100 (range 0-8). 57/66 nausea scores collected have been zero. There have been no clinically-significant APD421-related adverse events. Recruitment will continue until the desired sample size of 23 subjects is reached (expected to be completed July 2012). Final results will be presented.

Conclusions

The acute-phase efficacy of APD421 in combination with ondansetron in CINV compares favourably with historical data on other 5-HT3-based combinations. Randomised trials in acute and delayed phase CINV are merited.

Disclosure

G. Fox: The author is an employee and stock-holder of Acacia Pharma.

All other authors have declared no conflicts of interest.