An Interim Analysis of Phase II, Open Randomized Comparative Trial: Alternate or Multiple-Day Dosing of Palonosetron (PALO) Is Effective and Safe in the Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) in Patients (pts) with Leukemia Receiving High Dose Ara-C (HDAC).

Background: CINV is a significant problem for pts with leukemia undergoing multiple-day, high-dose chemotherapy (MD-HD-CHEMO). (PALO) has higher binding affinity to 5-HT3 receptors, higher potency and longer half-life than first generation 5-HT3 receptor antagonists, which, in addition, are not effective in preventing delayed CINV.

Study Objectives: To compare if PALO given in alternate doses or in multiple-day dosing is better than ondansetron (ONDA) given daily in the prevention of CINV in pts with AML/HR-MDS receiving MD-HD-CHEMO with HDAC containing regimens (AraC =1.5 or 2gm/m2 for 3–5 days).

Methods: Eligible pts were randomized to receive 30 minutes before CHEMO: ONDA: 8 mg IV bolus, then 24mg IV, continuous infusion on d1 through d5 and for 12 hours after Ara C infusion ends [ONDA 1–5]; or PALO 0.25mg IV bolus over 30 seconds, on d1 through d5 of Ara C infusion, [PALO 1–5]; or PALO 0.25mg IV bolus over 30 seconds, on day 1,3, and 5 of Ara C infusion (PALO 1,3,5). All patients received Solumedrol 40 mg IV before AraC. Complete response (CR) was defined as no emesis and no use of rescue medication (RM) during the administration of chemo and up to 7 days; Complete control (CC) was define as CR + pts with ≤ 1 episode of emesis within 24 hours and no more than moderate nausea with no need of RM for either case. Failure (F) was defined as the needs to use of RM. Pts were followed for 7 days. A diary to evaluate impact of CINV on daily activities was filled by the pts during the 7 days. Hereby we present data in the first 95 evaluable patients. The 3 group of pts were comparable in regards to age, gender, race, performance status, history of alcohol use and smoking habits. Response rates are shown in the table below. Although not statistically significant (p= 0.178), less pts in either PALO arm had CINV on day 1 (28%, 10% and 22 for ONDA 1–5, PALO 1–5 and Palo 1,3,5, respectively). In addition, more patients in PALO 1–5 reported none or mild nausea on days 6 (p= 0.023) and 7 (p= 0.139). No grade 3/4 side effects were reported. Five pts had Grade 2 constipation (PALO 1–5= 3; PALO 1,3,5 = 2), and 1 other pt in the PALO 1–5 had grade 2 headache.

Conclusions: Palonosetron given on days 1, 3 and 5 or in multiple-day dosing is effective and safe for the prevention of CINV in pts with AML or HR-MDS receiving multiple-day high-dose ARA C chemotherapy.