title: Sustained antiemetic responses with APF530 (sustained-release granisetron) during multiple cycles of emetogenic chemotherapy.
abstract: BACKGROUND
  A phase 3 trial in patients with cancer who received chemotherapy has shown that subcutaneous (SC) APF530, a sustained-delivery formulation of granisetron, is noninferior to palonosetron in preventing acute (0-24 hours) and delayed (>24-120 hours) chemotherapy-induced nausea and vomiting (CINV).
  
  
  OBJECTIVE
  To investigate the sustainability of APF530 antiemetic responses during multiple chemotherapy cycles.
  
  
  METHODS
  1,395 patients receiving moderately or highly emetogenic chemotherapy (MEC and HEC, respectively) were randomized either to APF530 250 or 500 mg SC (containing granisetron 5 or 10 mg, respectively) or palonosetron 0.25 mg intravenously before cycle 1 of chemotherapy. Patients who received palonosetron in cycle 1 were rerandomized in cycles 2-4 to APF530 250 or 500 mg; those who received APF530 in cycle 1 continued their APF530 dose. Between-group response rates were compared using the Fisher exact test.
  
  
  RESULTS
  Complete response (CR; no emesis, no rescue medication) for APF530 500 mg with HEC increased from 81.3% to 87.8% over 4 cycles in the acute phase of CINV, and from 67.1% to 83.1% in the delayed phase. Rates were slightly lower with MEC. Within-cycle CR rates between APF530 doses showed no significant differences. With HEC, APF530 500 mg provided sustained CRs through 4 cycles of chemotherapy in 68.4% of patients in the acute phase and in 57.9% in the delayed phase; with MEC, corresponding CRs were 56.5% and 41.3%. Nausea prevention was nearly as effective as emesis prevention.
  
  
  CONCLUSIONS
  Chemotherapy emetogenicity was classified according to Hesketh criteria during the time of this study. However, subsequent post hoc analyses indicate that reclassification according to newer ASCO emetogenicity guidelines did not alter the original study noninferiority conclusions.
  
  
  CONCLUSIONS
  CR rates with APF530 during the acute and delayed phases of CINV in MEC and HEC were maintained over multiple cycles.
authors: Center for Cancer and Blood Disorders, Bethesda, Maryland, USA. rboccia@ccbdmd.com.
authors: Ralph
authors: R
authors: Boccia
authors: TFS International, Flemington, New Jersey, USA.
authors: William
authors: W
authors: Cooper
authors: FebroGen Inc, San Francisco, California, USA.
authors: Erin
authors: E
authors: O'Boyle
keywords: CINV; cancer; chemotherapy-induced nausea and vomiting; extended release; granisetron; subcutaneous