Schwartzberg, L., Jackson, J., Jain, G., Balu, S., & Buchner, D. (2011). Impact of 5-HT(3) RA selection within triple antiemetic regimens on uncontrolled highly emetogenic chemotherapy-induced nausea/vomiting. Expert Review of Pharmacoeconomics & Outcomes Research, 11(4), 481–488.

To assess the likelihood of uncontrolled chemotherapy-induced nausea and vomiting (CINV) events following antiemetic prophylaxis with the 5-HT₃ receptor antagonist (RA) palonosetron plus aprepitant or fosaprepitant and dexamethasone versus any of the other 5-HT₃ RAs (granisetron, dolesetron, ondansetron) plus aprepitant or fosaprepitant and dexamethasone among single-day, highly emetogneic chemotherapy (HEC) cycles

This was a retrospective analysis of a healthcare claims database from January 2006 through June 2010 using data from International Classification of Diseases book 9 (ICD-9), Current Procedural Terminology (CPT), and pharmacy claims. Investigators evaluated two cohorts. The palonosetron cohort consisted of patients initiating antiemetic prophylaxis with palonosetron plus aprepitant or fosaprepitant and dexamethasone. The \"other 5-HT₃ cohort\" consisted of patients receiving any other 5-HT₃ RA plus aprepitant or fosaprepitant and dexamethasone.

• In all, 4,552 patients met the selection criteria; 3,574 for the palonosetron cohort and 978 for the other 5-HT₃ cohort. Mean age was 53 years.
• The sample was 23% male and 77% female.
• To be included in the study, patients could be diagnosed with any cancer but must have received treatment with a single-day, HEC regimen (defined as chemotherapy administrations with at least a 5-day gap between two consecutive administrations). Breast cancer was the predominant malignancy (n = 2,313, approximately 50%) followed by “multiple cancers” (n = 1,282, approximately 30%). All HEC-treated patients were required to have received a prophylactic antiemetic regimen that included a 5-HT₃ plus dexamethasone plus fosaprepitant or aprepitant regimen.
• In the database, the payer-type distribution was 80% commercial, 15% other, 3% Medicaid, and 1.7% Medicare Risk. All patients included in the database were eligible for medical and pharmacy benefits.

Patients were undergoing the active treatment phase of care.

This was a retrospective data analysis.

CINV was defined as at least one of the following during days 2–5 post chemotherapy: a diagnosis of nausea or vomiting (ICD-9 code); hydration procedure (CPT code); rescue medication use of any of the following: dexamethasone, diphenhydramine, olanzapine, promethazine, haloperidol, prochlorperazine, lorazepam, or metoclopramide; or antiemetic administration of palonosetron, ondansetron, granisetron, dolasetron and fosaprepitant/aprepitant by oral or IV routes.

A total of 8,018 cycles for the palonosetron cohort and 1,926 cycles for the other 5-HT₃-RA cohort were analyzed. Single-day HEC cycles received by the palonosetron cohort had a significantly lower unadjusted risk of an uncontrolled CINV event with a 17% lower risk for palonosetron-administered cycles versus 21% risk for other 5-HT₃ RAs (p = 0.0010). Results in the breast cancer and multiple cancer subgroups were consistent with those for the overall population.

This study suggests that all 5-HT₃ RAs may not be equivalent in preventing delayed CINV for patients receiving single-day HEC; however, the study design limits the strength of the evidence.  

• No appropriate control group was included.
• The study is limited in its design because retrospective database analysis does not allow for assessment of potential differences between cohorts in terms of patient history of CINV-predictive factors such as alcohol use and motion sickness.
• The study does not evaluate multiple-day regimens of HEC. 
• The data were taken from claims with the assumption that patients billed for antiemetic medications, prescriptions, or hydration experienced an “uncontrolled CINV event” and patients that did not have this same associated claim data did not have an uncontrolled CINV event. However, this does not reflect the practice styles of prescribers or patient reports. Some prescribers routinely give patients oral rescue antiemetic prescriptions and have them filled prior to the start of treatment. Additionally, patients may have had unreported or untreated CINV or may have taken prophylactic treatment without actually experiencing uncontrolled CINV. 
   

Nurses may want to consider substituting palonosetron as 5-HT₃ in antiemetic regimen for single day HEC.