Efficacy and safety of olanzapine combined with aprepitant, palonosetron, and dexamethasone for the prevention of cisplatin-based chemotherapy-induced nausea and vomiting for gynecological cancer: KCOG G-1301 phase II trial.

TPS9639 Background: Olanzapine is proved to be effective for chemotherapy-induced nausea and vomiting (CINV). But its preventive efficacy in combination with standard antiemetic therapy (palonosetron, aprepitant, and dexamethasone) is unknown. The purpose of this study is to prove the preventive effect of olanzapine for the prevention of CINV caused by highly emetogenic chemotherapy (HEC) when used with standard antiemetic therapy. We started a prospective multicenter phase II study at six facilities related to Kansai Clinical Oncology Group (KCOG) since September 2013. Methods: Chemo-naïve patients aged 20-79 years old is enrolled. They are gynecologic cancer patients who are treated with HEC regimen containing cisplatin (more than 50 mg/m2). Target sample size is 40. Since olanzapine is contraindicated in patients with diabetes mellitus, their blood sugar level and HbA1c are checked to confirm that they do not have glucose intolerance before treatment. All patients are informed of drug information and the consent of using olanzapine are obtained. Aprepitant is administered at a dose of 125 mg before chemotherapy on day 1 and at 80 mg on days 2 and 3. Palonosetron (0.75 mg) is given before chemotherapy on day 1. Dexamethasone is administered at a dose of 9.9 mg before chemotherapy on day 1 and at 6.6 mg on days 2–4. 5mg oral olanzapine is administered for 6 days from the day before chemotherapy. All of patients record the self-evaluation diary about their emesis every 24 h throughout the overall phase (0–120 h after cisplatin). The primary endpoint is the proportion of patients with a complete response (no vomiting and no rescue therapy) throughout the overall phase. The secondary endpoints are the proportion of patients with complete response in the acute phase (0–24 h after cisplatin) and in the delayed phase (24–120 h after cisplatin) of the study, as well as the proportion of patients with complete control (no vomiting, no rescue therapy, no significant nausea (numeric rating scale 0-2)) and total control (no vomiting, no rescue, no nausea) throughout the study and in the acute and delayed phases. Clinical trial information: UMIN000011857.