Celio, L., Agustoni, F., Ricchini, F., Dotti, K., Niger, M., & Braud, F.D. (2013). Palonosetron plus dexamethasone in highly emetogenic chemotherapy: Pooled data from two phase III trials. Future Oncology, 9(10), 1451–1458. 

To compare the effectiveness of palonosetron combined with dexamethasone versus older antagonist-containing regimens in combination with dexamethasone in patients receiving highly emetogenic chemotherapy (HEC)

In both studies, eligible patients were randomly assigned to receive a single IV dose of palonosetron (0.25 mg or 0.75 mg), or an older antagonist (Zofran® 32 mg or granisetron 3 mg) as a bolus given 30 minutes before initiation of HEC on day 1. Prophylactic dexamethasone (20 or 16 mg IV) was administered before the initiation of chemotherapy on day 1. In the Saito et al. trial, one of the trials summarized by Celio et al., delayed dexamethasone was also given daily on days 2 and 3. The primary endpoint for efficacy was the proportion of patients achieving CR (defined as no emetic episodes and no use of rescue antiemetics). Patients recorded daily emetic events, nausea, and rescue medications for five days after starting chemotherapy.

• N = 1411
• MEAN AGE = 55–56 years
• MALES: 43.1%, FEMALES: 56.9%
• KEY DISEASE CHARACTERISTICS: Lung/breast/other malignancies scheduled to receive a single dose of IV HEC

• SITE: Multi-site  
• SETTING TYPE: Multiple settings  
• LOCATION: Japan and western countries

• PHASE OF CARE: Active antitumor treatment

Pooled analysis of multi-center, double-blind, double-dummy, parallel-group, active-comparator trials

Patient daily diary recording emetic events, severity of nausea, and rescue medication use

The proportion of patients achieving CR was significantly higher with the palonosetron versus the control regimen in the overall five-day study period (49.2% versus 37.3%; p < 0.0001), in the acute phase (73.1% versus 69.7%), as well as in the post hoc analysis for the delayed time period (53.6% versus 41.2%; p < 0.0001). For either time period, the incremental improvement observed with the use of palonosetron was approximately 12 percentage points.

The analysis of data from two pooled studies demonstrates the benefit of palonosetron plus dexamethasone, compared to older 5-HT3 receptor antagonists plus dexamethasone, in the prevention of chemotherapy-induced nausea and vomiting (CINV) in HEC during a five-day study period. It also suggests a benefit of palonosetron on delayed nausea or vomiting.

• Risk of bias (no control group)
• Other limitations/explanation: Different doses of dexamethasone were given in standard care group.

This study further supports prior data showing that palonosetron with dexamethasone provides improved protection from overall CINV during HEC, as well as in the delayed phase, over older-generation 5-HT3 receptor antagonists.