Mattiuzzi, G.N., Cortes, J.E., Blamble, D.A., Bekele, B.N., Xiao, L., Cabanillas, M., … Kantarjian, H. (2010). Daily palonosetron is superior to ondansetron in the prevention of delayed chemotherapy-induced nausea and vomiting in patients with acute myelogenous leukemia. Cancer, 116, 5659–5666.

To compare the efficacy of two schedules of palonosetron versus ondansetron given by continuous IV infusion for treatment of chemotherapy-induced nausea and vomiting (CINV)

• Patients were randomly assigned to 1 of 3 intervention arms.
  • 8 mg of ondansetron IV bolus over 15 minutes followed by 24 mg of ondansetron given by continuous IV infusion starting 30 minutes before chemotherapy and lasting until 12 hours after chemotherapy infusion ended
  • 0.25 mg of palonosetron as IV bolus over 30 seconds, 30 minutes before start of chemotherapy daily during the chemotherapy cycle
  • 0.25 mg palonosetron as an IV bolus over 30 seconds, 30 minutes before the start of chemotherapy on days 1, 3, and 5 of treatment.
• All patients received 40 mg methylprednisolone as an IV bolus before each cytarabine infusion.
• Patient diaries were used to record episodes of vomiting, severity of nausea, use of rescue medication, and degree of impact on daily activities.
• Patients were followed for 7 days.

• The sample consisted of 143 patients.
• Median age was 53 years.
• The sample consisted of 47.6% female and 52.4% male patients.
• All subjects had acute myeloid leukemia, and all but five patients were undergoing induction therapy with idarubicin plus cytarabine or fludarabine plus cytarabine.

The study was conducted at an inpatient setting at the University of Texas M.D. Andersen Cancer Center.

All patients were in active treatment.

This was a randomized prospective study.

• Patients recorded nausea and vomiting severity in diaries.
• Nausea severity was measured on a Likert-type scale.
• Complete response (CR) was defined as no emesis and no use of rescue medications.
• Partial response (PR) was defined as one or fewer emesis episodes, no use of rescue medication during the study, and no more than grade 2 nausea.

• No significant difference was found in the proportion of patients who achieved a CR among groups.
• On day 1, more than 77% of patients in each group were free of nausea. The proportion of patients without nausea was similar across groups on days 2 through 5. On days 6 and 7, more patients receiving palonosetron than ondansetron were free of nausea (p < 0.03).
• No between-group differences in severity of nausea were recorded during days 1–5.
• Predictors of nausea in multivariate analysis were younger age, (p = 0.02), high-dose cytarabine plus idarubicin (p = 0.04), and prophylactic antibiotics (p = 0.009).
• The most commonly reported adverse events were headache and constipation.

Palonosetron was superior to ondansetron in reducing the prevalence of delayed nausea.

The study has potential bias because no control group or blinding was used.

Daily palonosetron appears to be more effective than the alternative used here for the prevention of delayed nausea. All the regimens here were similar in the early days of the therapy course, but palonosetron was significantly better in later days. Findings suggest that different drugs might be more helpful on different days throughout the course of chemotherapy, in concert with patterns seen in nausea.