Craver, C., Gayle, J., Balu, S., & Buchner, D. (2011). Palonosetron versus other 5-HT₃ receptor antagonists for prevention of chemotherapy-induced nausea and vomiting in patients with hematologic malignancies treated with emetogenic chemotherapy in a hospital outpatient setting in the United States. Journal of Medical Economics, 14(3), 341–349.

To evaluate the rate of uncontrolled chemotherapy-induced nausea and vomiting (CINV) after initiation of antiemetic prophylaxis with palonosetron as compared to all other 5-HT₃ antagonists in patients diagnosed with hematologic malignancies and receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC)

Subjects who were 18 or older, were identified from eight million cancer discharges that are part of the Premier Perspective Database, which includes data from more than 600 hospital systems. After establishing the correct diagnosis and pharmacologic treatment, data were retrospectively extracted from the database from initiation of chemotherapy to the end of eight rounds of chemotherapy treatment or for six months. 

• This study reported on 971 patients with a mean age of 61.9 years.
• The sample was 48% male and 52% female.
• Primary hematologic malignancies were defined as lymphoma (79%), myeloma (6.4%), and leukemia  (AML , CML, ALL, CLL, and other leukemia, 14%).   
• Patients were chemotherapy naïve, with no prior evidence of nausea or vomiting.
• Patients had hematologic malignancies and were initiated with single or multiday chemotherapy and antiemetic prophylaxis with palonosetron (group 1) or all other 5-HT₃ antagonists (group 2). The sample was 71.2 % white. Patients who received palonosetron represented 22% of the sample.

This was a multisite, outpatient study based on the Premier Perspective Database containing data from more than 600 hospitals.

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

This was a longitudinal, retrospective observational study.

The primary study outcome was rate of uncontrolled CINV events in the study follow-up period of eight cycles of chemotherapy or six months, with events operationally defined by either the need for rescue antiemetics on day two or by any of the ICD-9 codes for nausea, vomiting or volume depletion, dehydration, or hypovolemia. The unit of analysis was one cycle, defined as number of treatments in seven days.

• Of 971 subjects for whom data were extracted, 211 subjects were treated initially with palonosetron and 760 subjects were treated with other 5-HT₃ antagonists.  The groups were comparable in most aspects, including the Charlson Comorbidity Index (mean CCI = 0.2); however, group 1 had a higher percentage of patients who received HEC.
• After adjusting for baseline differences in the two groups, multivariate analysis results predicted a 20.4% lower CINV event rate per chemotherapy cycle in patients with hematologic malignancies treated with palonosetron. This difference was slightly more than one episode per cycle. No significant differences were found in the actual event rate from analysis. 
• Females were shown to have a higher CINV rate, but it was not statistically significant.
• Cycle length (total days within week) also was found to be associated with CINV, with increased days leading to more CINV.

Patients treated with palonosetron in the outpatient setting had significantly lower CINV event rates (decrease of 20%) versus patients treated with other 5-HT₃ antagonists after adjusting for baseline differences.  However, because this study did not look at the contribution of other antiemetics (e.g., aprepitant, dexamethasone), we may only conclude that in a fairly large sample of patients from the Premier Perspective Database, the group of patients who were given palonosetron on the initiation of HEC or MEC experienced less CINV.

• A retrospective study design relies on the accurate documentation of events by others; however the large sample size is definitely a plus.  
• Using a combined data set pulls patients from many practices, the researchers cannot control for variation in clinical practices. We do not know why palonosetron was chosen originally.
• The use of other antiemetics were not considered, including corticosteroids and the neurokin 1 (NK1) receptor antagonist aprepitant, which may have an impact on the study results.
• We do not know the patients' histories of previous nausea and vomiting, motion sickness, smoking history, or how much medication was given.

Palonosetron should be considered for the prevention of CINV in patients with hematologic malignancies being treated with HEC or MEC.