Celio, L., Denaro, A., Agustoni, F., & Bajetta, E. (2012). Palonosetron plus 1-day dexamethasone for the prevention of nausea and vomiting due to moderately emetogenic chemotherapy: Effect of established risk factors on treatment outcome in a phase III trial. The Journal of Supportive Oncology, 10(2), 65–71.

To verify whether the noninferiority hypothesis of a dexamethasone sparing regimen can be demonstrated even after adjustment for known risk factors for developing CINV and to assess the impact of the risk factors studied on antiemetic outcome

Chemotherapy-naïve patients received 0.25 mg IV palonosetron and 8 mg IV dexamethasone on day 1. Patients were randomly assigned to no additional dexamethasone (1 day dexamethasone regimen) or 8 mg oral dexamethasone on days 2–3 (3-day dexa regimen). After chemotherapy, rescue medication, including dexamethasone or metoclopramide, were permitted on an as-needed basis.

• The study consisted of 324 patients with a median age of 57.5 years.
• The sample was 35% male and 65% female.
• Cancer diagnoses were primarily breast and colorectal with some lung and other.
• Patients were chemotherapy naïve receiving MEC (additional chemotherapeutic agents of Hesketh-emetogenic level 2 or lower were permitted between days 1–5) with a European Cooperative Oncology Group status of 0–2 (mostly 0–1).
• Patients receiving AC chemotherapy represented 35% of the sample, and 36% of patients had distant metastases.

The study was conducted at multiple sites (not specified) in Italy.

• All patients were in active treatment.
• This study has application to late effects and survivorship.

This was a prespecified, posthoc analysis of a randomized, multicenter, phase III trial.

• Complete response was defined as no emetic episodes and no rescue antiemetics during the overall five-day study period and no nausea in the overall study period.
• Risk factors of age, gender, and alcohol consumption were recorded.

• In the adjusted model (multivariable), only younger age (p = 0.044) was significantly associated with poorer outcomes in terms of CR to antiemetic treatment. As compared with older patients, those under 50 years of age had a probability of achieving complete protection against CINV in the overall five-day study period that was reduced by approximately 13 percentage points.
• No between-treatment differences were found in CR rates according to age, gender, alcohol consumption, and type of MEC regimen.
• No significant differences were found between treatment groups in the rate of no nausea according to each risk factor studied (among younger patients undergoing AC-based chemotherapy).
• The three-day regimen achieved higher nausea control than the one-day regimen (p = 0.075).

The analysis confirmed that the palonosetron plus one-day dexamethasone regimen provides a valid treatment option for prevention of CINV in delayed, non-AC-based MEC. However, these findings are not applicable to younger patients undergoing AC-based chemotherapy as the palonosetron plus three-day dexamethasone regimen achieved statistically better nausea control in this population.

Younger patients were mostly women undergoing AC chemotherapy and, primarily, no history of alcohol consumption.  A 15% margin was set for the noninferiority analysis, which is still a highly clinically relevant difference.

Administration of palonosetron with single-day dexamethasone could be recommended for the patients undergoing non-AC-based MEC for the control of delayed CINV, considering the side effects of dexamethasone. This was a noninferiority analysis, meaning that  researchers accepted a 15% difference in rate of control as no real difference. Nurses need to be aware of the implications of this type of trial and judge whether lack of CINV control in 15% of patients is acceptable.  As the study demonstrated, the palonosetron with three-day dexamethasone regimen is still recommended for the control of nausea, especially for younger patients receiving AC-based chemotherapy.