title: Randomized phase III trial of APF530 versus palonosetron in the prevention of chemotherapy-induced nausea and vomiting in a subset of patients with breast cancer receiving moderately or highly emetogenic chemotherapy.
abstract: BACKGROUND
  APF530 provides controlled, sustained-release granisetron for preventing acute (0-24 h) and delayed (24-120 h) chemotherapy-induced nausea and vomiting (CINV). In a phase III trial, APF530 was noninferior to palonosetron in preventing acute CINV following single-dose moderately (MEC) or highly emetogenic chemotherapy (HEC) and delayed CINV in MEC (MEC and HEC defined by Hesketh criteria). This exploratory subanalysis was conducted in the breast cancer subpopulation.
  
  
  METHODS
  Patients were randomized to subcutaneous APF530 250 or 500 mg (granisetron 5 or 10 mg) or intravenous palonosetron 0.25 mg during cycle 1. Palonosetron patients were randomized to APF530 for cycles 2 to 4. The primary efficacy end point was complete response (CR, no emesis or rescue medication) in cycle 1.
  
  
  RESULTS
  Among breast cancer patients (n = 423 MEC, n = 185 HEC), > 70 % received anthracycline-containing regimens in each emetogenicity subgroup. There were no significant between-group differences in CRs in cycle 1 for acute (APF530 250 mg: MEC 71 %, HEC 77 %; 500 mg: MEC 73 %, HEC 73 %; palonosetron: MEC 68 %, HEC 66 %) and delayed (APF530 250 mg: MEC 46 %, HEC 58 %; 500 mg: MEC 48 %, HEC 63 %; palonosetron: MEC 52 %, HEC 52 %) CINV. There were no significant differences in within-cycle CRs between APF530 doses for acute and delayed CINV in MEC or HEC in cycles 2 to 4; CRs trended higher in later cycles, with no notable differences in adverse events between breast cancer and overall populations.
  
  
  CONCLUSIONS
  APF530 effectively prevented acute and delayed CINV over 4 chemotherapy cycles in breast cancer patients receiving MEC or HEC.
  
  
  BACKGROUND
  Clinicaltrials.gov identifier: NCT00343460 (June 22, 2006).
authors.affiliation: Center for Cancer and Blood Disorders, 6410 Rockledge Drive #660, Bethesda, MD, 20819, USA. RBoccia@CCBDMD.com.
authors.forename: Ralph
authors.initials: R
authors.lastname: Boccia
authors.affiliation: FibroGen, Inc, 409 Illinois Street, San Francisco, CA, 94158, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: O'Boyle
authors.affiliation: TFS, Inc, 212 Carnegie Center, Suite 208, Princeton, NJ, 08540, USA.
authors.forename: William
authors.initials: W
authors.lastname: Cooper
mesh_terms: D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000150:complications* / Q000188:drug therapy; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009325:Nausea / Q000209:etiology* / Q000517:prevention & control*; D000077924:Palonosetron; D011812:Quinuclidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014839:Vomiting / Q000209:etiology* / Q000517:prevention & control*
chemical_list: D000932:Antiemetics; D007546:Isoquinolines; D011812:Quinuclidines; D000077924:Palonosetron