Gabrail, N., Yanagihara, R., Spaczynski, M., Cooper, W., O'Boyle, E., Smith, C., & Boccia, R. (2015). Pharmacokinetics, safety, and efficacy of APF530 (extended-release granisetron) in patients receiving moderately or highly emetogenic chemotherapy: Results of two phase II trials. Cancer Management and Research, 7, 83-92.

To determine the pharmacokinetics, safety, and efficacy of two dosing regimens of APF530

There were two separate studies reported in this paper. The first study included 45 patients and used three escalating dosing schedules of 250 mg, 500 mg, or 750 mg. The second study included 35 patients with two dosing schedules of 250 or 500 mg. Safety and efficacy were reported. Drug levels were measured from predose to 168 hours after administration. Doses were given via subcutaneous injection in the abdomen prior to chemotherapy. All patients also received dexamethasone.

• N = 80
• MEAN AGE = 64 years (SD = 12.5 years [trial 1]), 55.7 years (SD = 8.7 years [trial 2])
• MALES: 40% (trial 1), FEMALES: 60% (trial 1), 100% (trial 2)
• KEY DISEASE CHARACTERISTICS: Ovarian cancer, breast cancer, lung cancer, lymphoma, leukemia, endometrial cancer, cervical cancer, vulvar cancer, colorectal cancer, bladder cancer, thymoma, and myeloma
• OTHER KEY SAMPLE CHARACTERISTICS: Chemotherapy regimens included carboplatin and combinations of cyclophosphamide-anthracycline, cyclophosphamide combinations, irinotecan, topotecan, cisplatin combinations, anthracycline, and gemcitabine-vinorelbine, among others.

• SITE: Multi-site    
• SETTING TYPE: Outpatient  
• LOCATION: Gabrail Cancer Center in Canton, OH; St. Louise Regional Hospital in Gilroy, CA; Department of Gynecologic Oncology at the University of Medical Science in Poznan, Poland

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care and palliative care

Prospective

• Plasma concentrations were measured.  
• Safety was assessed by vital signs, physical examinations, and clinical laboratory tests.  
• Twelve lead electrocardiograms were completed at screenings.  
• Symptoms were assessed with patient diaries.  
• Effectiveness was measured using diaries, information about the use of rescue medications, the number of emetic episodes, the number of retching episodes, and the number of nausea episodes for a seven-day period after the administration of medications.  
• Noncompartmental methods and descriptive statistics were used.

Both studies met the primary objective by defining pharmacokinetics. Adverse events did not appear to be dose-related. Most were mild to moderate and were unrelated to the study drug. Injection site reactions were low and were not associated with dosing, and 17.7% of erythema was reported in the 250 mg arm. No erythema was reported in the 750 mg arm. The plasma concentrations of granisetron were maintained for seven days with a single dose of the drug. Preliminary data demonstrated another option for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. Patients treated with APF530 at 250 or 500 mg obtained complete response 83% of the time in the acute-onset and delayed-onset phases. Complete control was obtained in 76%. Nausea was controlled almost as well as emesis. Nausea reports were mostly mild.

Granisetron exposure was maintained for seven days with a single dose of subcutaneous AFP530. Mild injection site irritation was noted. Nausea was mild, and nausea and vomiting were controlled in the acute and delayed phases.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Risk of bias (no appropriate attentional control condition)  
• Findings not generalizable

This could be another option for treating chemotherapy-induced nausea and vomiting, but it is possible that this treatment causes unnecessary discomfort when oral and transdermal approaches are available. This is very preliminary data, and the study did not compare this treatment to standard care. Additional research to determine the usefulness of this drug for chemotherapy-induced nausea and vomiting is needed.