title: Pharmacokinetics, safety, and efficacy of APF530 (extended-release granisetron) in patients receiving moderately or highly emetogenic chemotherapy: results of two Phase II trials.
abstract: BACKGROUND
  Despite advances with new therapies, a significant proportion of patients (>30%) suffer delayed-onset chemotherapy-induced nausea and vomiting (CINV) despite use of antiemetics. APF530 is a sustained-release subcutaneous (SC) formulation of granisetron for preventing CINV. APF530 pharmacokinetics, safety, and efficacy were studied in two open-label, single-dose Phase II trials (C2005-01 and C2007-01, respectively) in patients receiving moderately emetogenic chemotherapy or highly emetogenic chemotherapy.
  
  
  METHODS
  In C2005-01, 45 patients received APF530 250, 500, or 750 mg SC (granisetron 5, 10, or 15 mg, respectively). In C2007-01, 35 patients were randomized to APF530 250 or 500 mg SC. Injections were given 30 to 60 minutes before single-day moderately emetogenic chemotherapy or highly emetogenic chemotherapy. Plasma granisetron was measured from predose to 168 hours after study drug administration. Safety and efficacy were also evaluated.
  
  
  RESULTS
  APF530 pharmacokinetics were dose proportional, with slow absorption and elimination of granisetron after a single SC dose. Median time to maximum plasma concentration and half-life were similar for APF530 250 and 500 mg in both trials, with no differences between the groups receiving moderately and highly emetogenic chemotherapy. Exposure to granisetron was maintained at a therapeutic level over the delayed-onset phase, at least 168 hours. Adverse events in both trials were as expected for granisetron; injection site reactions (eg, erythema and induration) were predominantly mild and seen in ≤20% of patients. Complete responses (no emesis, with no rescue medication) were obtained in the acute, delayed, and overall phases in ≥80% and ≥75% of patients in both trials with the 250 and 500 mg doses, respectively.
  
  
  CONCLUSIONS
  After a single injection of APF530, there were dose-proportional pharmacokinetics and sustained concentrations of granisetron over 168 hours. The 250 and 500 mg doses were well tolerated and maintained therapeutic granisetron levels for ≥5 days.
authors.affiliation: Gabrail Cancer Center, Canton, OH, USA.
authors.forename: Nashat
authors.initials: N
authors.lastname: Gabrail
authors.affiliation: St Louise Regional Hospital, Gilroy, CA, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Yanagihara
authors.affiliation: Department of Gynecology, Obstetrics and Gynecologic Oncology, University of Medical Sciences, Poznan, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Spaczyński
authors.affiliation: TFS International, Flemington, NJ, USA.
authors.forename: William
authors.initials: W
authors.lastname: Cooper
authors.affiliation: FibroGen, Inc., San Francisco, CA, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: O'Boyle
authors.affiliation: Gabrail Cancer Center, Canton, OH, USA.
authors.forename: Carrie
authors.initials: C
authors.lastname: Smith
authors.affiliation: Center for Cancer and Blood Disorders, Bethesda, MD, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Boccia
keywords: cancer; chemotherapy-induced nausea and vomiting; subcutaneous
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