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Cancer Manag Res. 2015 Mar 17;7:83-92. doi: 10.2147/CMAR.S72626. eCollection 2015.

Pharmacokinetics, safety, and efficacy of APF530 (extended-release granisetron) in patients receiving moderately or highly emetogenic chemotherapy: results of two Phase II trials.

Author information

1
Gabrail Cancer Center, Canton, OH, USA.
2
St Louise Regional Hospital, Gilroy, CA, USA.
3
Department of Gynecology, Obstetrics and Gynecologic Oncology, University of Medical Sciences, Poznan, Poland.
4
TFS International, Flemington, NJ, USA.
5
FibroGen, Inc., San Francisco, CA, USA.
6
Center for Cancer and Blood Disorders, Bethesda, MD, USA.

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.

CONCLUSION:

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.

KEYWORDS:

cancer; chemotherapy-induced nausea and vomiting; subcutaneous

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