Boccia, R., Grunberg, S., Franco-Gonzales, E., Rubenstein, E., & Voisin, D. (2013). Efficacy of oral palonosetron compared to intravenous palonosetron for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: a phase 3 trial. Supportive Care in Cancer, 21, 1453–1460.

To examine the efficacy of three different doses of oral palonosetron compared to IV palonosetron for chemotherapy-induced nausea and vomiting (CINV) management and to explore the contribution of dexamethasone to these regimens

Patients were randomized to one of four different groups: oral palonosetron at 0.25, 0.5, and 0.75 mg or IV palonosetron at 0.25mg. Within each of these groups, patients were randomized to receive a single 8 mg IV dose of dexamethasone or placebo. Patients were stratified by age and by whether they had received previous chemotherapy. All patients were receiving single day chemotherapy. The noninferiority margin for analysis was set at a maximum difference in complete response rate at 24 hour of 15%.

• The study looked at 635 patients with a mean age of 56.7 years.
• The sample was 47% male and 53% female.
• Diagnoses were breast, colon, and lung.  All patients were receiving single-day, moderately emetogenic chemotherapy (MEC).
• Most patients were Caucasian or Hispanic.  Slightly more than half were chemotherapy naïve.

This was a multisite study conducted in outpatient settings in multiple countries.

All patients were in active antitumor treatment.

This was a randomized, double-blind, double-dummy trial.

• Complete response (CR) in the acute, delayed and overall phases was defined as no emesis and no rescue antiemetics.
• Nausea severity was rated on 4-point, Likert-type scale.

• In the acute phase, all of the oral doses were shown to not be inferior to IV palonosetron. In the delayed phase, none of the oral doses reached noninferiority to the IV dose.  In the overall phase, (0-120 hours postchemotherapy), only the 0.5 mg oral dose was found to be noninferior.
• CR was 77%–83% in the acute phase, 68%–75% in the delayed phase, and 61%–70% in the overall phase. 
• No differences were found across palonosetron groups in nausea.
• In general, in both the acute and delayed phases, subgroups that also received dexamethasone showed higher CR rates. 
• Use of rescue antiemetics was similar across study groups.  
• Adverse events were comparable across groups, with no apparent dose-response relationship.

Both oral and IV palonosetron formulations were shown to be effective in CINV prevention, and similar effects were seen at all three oral doses studied.  IV palonosetron may be more effective for reduction in CINV during the delayed phase. The addition of dexamethasone was associated with improved CR rates for both acute and delayed CINV.

• The measurements and methods were not well described.
• The findings are not generalizable.
• Other limitations include that the timing and method of nausea measurement were not well described and the findings are applicable to single-day MEC only.

Findings show that effectiveness of oral and IV palonosetron is similar, though the IV formulation may be slightly more effective for prevention of CINV during the delayed phase.   Findings also show that dexamethasone improves CINV control. Further research with multiday chemotherapy regimens and other emetogenic chemotherapy levels is warranted.  Findings continue to show that nausea is not as well controlled as emesis. High quality assessment of CINV in both acute and delayed phases is essential to ongoing planning for the most effective antiemetic approach for individual patients. A continued need exists to find effective interventions to reduce nausea as well as emesis.