Palonosetron Prevents Delayed CINV in Patients with AML

A study presented at the 51st American Society of Hematology Meeting and Expedition reported that 5 days of palonosetron (Aloxi) was significantly more effective than ondansetron at preventing delayed chemotherapy-induced nausea and vomiting (CINV) in patients with acute myelogenous leukemia (AML). Both drugs had similar efficacy in preventing acute CINV.

Very few agents are effective at preventing delayed emesis. The National Comprehensive Cancer Network (NCCN) guidelines state that “Ondansetron, granisetron, and dolasetron are effective in preventing acute emesis but appear to be less effective for delayed emesis” and note that intravenous (IV) palonosetron is effective at preventing acute and delayed emesis. The study by investigators from M.D. Anderson Cancer Center in Houston, Texas, supports these statements from NCCN for the AML patient population.

The authors explained that while patients with hematologic malignancies often experience CINV, it has only been weakly investigated. They had three objectives: compare alternate dosing or multiple-day dosing with palonosetron to ondansetron in patients receiving a multi-day, high-dose regimen containing cytarabine; evaluate the incidence of CINV in patients with AML; and identify risk factors for CINV.

Approximately one-third of the enrolled patients (n = 47) were randomized to receive 8 mg of ondansetron IV bolus 30 minutes prior to chemotherapy followed by 24 mg of ondansetron IV on day 1 up to day 5 (ONDA 1-5 arm). One-third (n = 48) received .25 mg of palonosetron IV bolus on day 1 up to day 5 of chemotherapy (PALO 1-5 arm), and the remaining one-third of patients (n = 48) received the same dose of palonosetron but only on days 1, 3, and 5 of chemotherapy (PALO 1,3,5 arm). All patients in the study received 40 mg of intravenous methylprednisolone each day prior to chemotherapy administration. For 1 week after completing chemotherapy, patients were asked to diary how CINV affected their daily activities.

At the end of the study period, 143 patients were evaluable for response. In assessing efficacy of the antiemesis medications, patients were considered to have complete response (CR) if they had no emesis and did not use rescue medication during chemotherapy and in the 7 days after chemotherapy. Complete control (CC) included patients demonstrating CR plus those with ≤1 episode of emesis within 24 hours and moderate nausea at most, with no need for rescue medication. The investigators defined failure as any need for rescue medication.

On day 1, when nausea was the greatest, the percentage of patients without nausea was similar across all three arms (P = .50), though response was slightly higher for patients taking palonosetron. CC was higher for patients in both palonosetron groups compared with the ondansetron group. On days 2 through 5, each arm experienced a steady decline in the proportion of patients who experienced nausea, according to investigators. For days 6 and 7, patients in the PALO 1-5 arm had a significantly lower incidence of nausea compared with those in the ONDA 1-5 arm and the PALO 1,3,5 arm (P = .0001 and .024, respectively). Patients in the PALO 1-5 arm were also less likely to need rescue medication on days 6 and 7 compared with patients in the ONDA 1-5 and the PALO 1,3,5 arms (P = .034 and .0350, respectively). Overall, a greater percentage of patients treated with ondansetron failed than those taking either dosing regimen of palonosetron, but researchers said the difference was not significant.

Based on patients’ diaries, significantly more patients in the PALO 1-5 group documented “none” or “mild” nausea on the final 2 days of follow-up compared with the ONDA 1-5 and the PALO 1,3,5 arms (P = .039 and .219, respectively). In addition, more patients in the PALO 1-5 group said CINV had minimal impact on their daily activities on day 6 (P = .0229).

The researchers conducted a univariate analysis and identified female sex, younger age, good performance status, the addition of idarubicin to chemotherapy, and use of prophylactic antibiotics as factors corresponding with an increased risk of developing chemotherapy-induced nausea. Multivariate analysis found that only younger age, a chemotherapy-regimen containing idrarubicin, and prophylactic antibiotic use were significantly associated with an increased likelihood of chemotherapy-

induced nausea.

The authors concluded that administering palonosetron for 5 days is “significantly better than ondansetron in the prevention of delayed CINV.” Although the regimens were similarly effective at preventing CINV in the acute phase, the authors said all 5HT3 antagonists continue to be “sub-optimal” at controlling nausea after day 1 of chemotherapy in this particular multi-day regimen and that new strategies are required.

Mattiuzzi G, Cortes J, McCue D, et al. Palonosetron given daily for up to 5 days is significantly better than ondansetron in the prevention of delayed CINV in patients with acute myelogenous leukemia. Presented at: 51st Annual ASH Meeting and Symposium. December 5, 2009; New Orleans, LA.