Celio, L., Frustaci, S., Denaro, A., Buonadonna, A., Ardizzoia, A., Piazza, E., … Italian Trials in Medical Oncology Group. (2010). Palonosetron in combination with 1-day versus 3-day dexamethasone for prevention of nausea and vomiting following moderately emetogenic chemotherapy: A randomized, multicenter, phase III trial. Supportive Care in Cancer,19, 1217–1225.

To assess the efficacy of palonosetron plus dexamethasone given once in preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV) with moderately emetogenic chemotherapy (MEC) regimens

All patients received a single IV dose of 0.25 mg palonosetron and 8 mg dexamethasone before chemotherapy on day 1. Patients then were randomized to one of two delayed antiemetic regimens: no additional dexamethasone or 8 mg dexamethasone daily on days 2 and 3. Rescue medication of dexamethasone or metoclopramide was allowed as needed. In patient diaries, participants recorded emetic events, use of rescue medication, and maximum nausea experience.

• The study consisted of 332 participants.
• In the palonosetron plus dexamethasone, one-day group, the mean age was 56.9 years (SD = 11.8). In the palonosetron plus dexamethasone, three-day group, the mean age was 57.2 years (SD = 11.3).
• The sample was 65.1% female and 34.9% male.
• Cancer diagnoses were breast, colorectal, lung, or other.
• Patients were chemotherapy naïve.
• Most patients received oxaliplatin or anthracycline plus cyclophosphamide (AC)–based chemotherapy regimens.

The study was conducted in multiple sites in Italy.

All patients were in active treatment.

This was a randomized, open-label, parallel group trial.

Patients recorded the number and time of emetic episodes, use of rescue medications, maximum nausea in the previous 24 hours, adverse events, and use of concomitant medication in patient diaries.

The following were measured.

• Complete response (CR), defined as no emetic episodes, no rescue medication, during days 1–5
• CR in acute and delayed phase
• Complete control (CC), defined as no emetic episodes, no use of rescue medication, no more than mild nausea
• No emesis, no nausea, and no use of rescue medication in overall, acute, and delayed phases
• Severity of nausea on a four-point Likert-type scale.

• No significant differences in CR rate were found between study groups in the overall, acute, and delayed phases.
• During the delayed phase, significantly fewer patients who had received three days of dexamethasone required rescue medication (p = 0.026).
• Overall, 83%–87% of patients achieved CC in the acute phase.
• In the delayed phase, 66.3% who received 1 day of dexamethasone had CR, compared to 75.8% of those who had three days of dexamethasone. These differences were not statistically significant.
• The proportion of patients with no vomiting and no nausea was not different between groups.
• Female gender and AC-containing chemotherapy were associated with worse overall CR rates across all subjects (p = 0.02).
• No clinically relevant differences were found between groups with respect to adverse events.

Palonosetron plus single-dose dexamethasone administered before common MEC regimens was not as effective as palonosetron plus dexamethasone for three days in the prevention of CINV.

• The percentage of patients who received AC chemotherapy (HEC) was 35.2% (subanalysis was done).
• The discussion states that the one-day regimen with palonosetron was more effective; however, data did not support that conclusion.
• Article discussion suggested bias.

For patients receiving non-AC MEC chemotherapy, and especially male patients, single-dose palonosetron and dexamethasone could be an option, considering side effects from multiday use of dexamethasone. However, as the study suggested, the need for rescue medication was higher in this group compared with the three-day dexamethasone regimen during the delayed phase.