Boccia, R., Cooper, W., & O'Boyle, E. (2015). Sustained antiemetic responses with APF530 (sustained-release granisetron) during multiple cycles of emetogenic chemotherapy. Journal of Community and Supportive Oncology, 13, 38–46.
To determine if a response to antiemetic APF530 is sustained over multiple cycles of chemotherapy
This study consisted of three treatment arms. During cycle 1, group 1 received 250 mg of subcutaneous APF530, group 2 received 500 mg of subcutaneous APF530, and group 3 received palonosetron at 0.25 mg IV in addition to an subcutaneous placebo before moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC). Patients receiving MEC also received dexamethasone at 8 mg IV 30–90 minutes before chemotherapy. Patients receiving HEC were given 20 mg of IV dexamethasone followed by 8 mg orally twice per day on days 2–4. In cycles 2–4, palonosetron was discontinued, and all patients in the palonosetron group were randomized to receive either 250 mg or 500 mg of APF530 with dexamethasone (dosing as previously stated). Cycles were separated by a range of 3–28 days. Rescue antiemetics were allowed as needed. Local anesthetic was administered to the injection site before the study drugs were administered. Study subjects kept diaries of emetic episodes, the use of rescue medications, and the severity of nausea for each 24-hour period after receiving chemotherapy. Adverse events were documented according to standard toxicity criteria. Complete response (CR) was defined as no rescue medications and no emetic episodes. Complete control (CC) was defined as no more than mild nausea and no rescue medications. Total response was defined as no nausea and no rescue medications.
Prospective, multicenter, randomized, double-blinded, placebo-controlled, parallel-group, phase 3 trial with stratification according to the emetogenicity of regimens
In cycle 1, ≥ 75% of both doses of APF530 had acute-phase CR, and ≥ 50% had delayed-phase CR. There was a similar response rate for cycles 2–4 with the HEC group having a slightly better response than the MEC group. Acute phase CR increased over the four cycles of HEC (81%–88%) for APF530 500 mg dose and CR increased from 67% to 83% in the delayed phase for this group. In patients who received palonosetron in cycle 1, ≥ 90% of those who had CR maintained CR in subsequent cycles (with APF530). Half of the of MEC and palonosetron group that did not achieve CR in cycle 1 achieved CR in next cycle (with APF530). No treatment-related serious adverse events were seen. Common adverse events across all cycles included constipation, headache, fatigue, and diarrhea for patients who received APF530. APF530 at 250 or 500 mg caused injection site reactions. Most were mild, and greater than than 3% were moderate.
This study demonstrated sustained responses in the acute and delayed phases of chemotherapy over four cycles in both 250 mg adnd 500 mg oses of APF530. Patients who responded to APF530 in cycle 1 also responded in cycles 2–4. Patients receiving palonosetron for chemotherapy-induced nausea and vomiting had a similar response to APF530 in subsequent cycles. Patients receiving APF530 had mild adverse effects primarily related to injection site reactions.
APF530 was an effective 5HT3 blocker for the prevention of chemotherapy-induced nausea and vomiting in HEC and MEC regimens, and its efficacy was sustained over multiple cycles. There was no significant benefit in using higher doses over the 250 mg dose. There was a potential for injection site reactions caused by the subcutaneous route of APF530, which may affect patients' quality of life.