Impact of 5-HT3 receptor antagonists on chemotherapy-induced nausea and vomiting: a retrospective cohort study.

Swu-Jane Lin,Hind T Hatoum,David Cox,Deborah Buchner,Sanjeev Balu

doi:10.1186/1472-6963-12-215

Abstract

Background1st generation 5-hydroxytryptamine receptor antagonists (5-HT3 RAs), and palonosetron, a 2nd generation 5-HT3 RA, are indicated for the prevention of chemotherapy (CT)-induced nausea and vomiting (CINV) associated with moderately (MEC) and highly emetogenic CT agents (HEC). This study explores the impact of step therapy policies requiring use of an older 5-HT3 RA before palonosetron on risk of CINV associated with hospital or emergency department (ED) admissions.MethodsPatients who received cyclophosphamide post breast cancer (BC) surgery or who were diagnosed with lung cancer on carboplatin (LC-carboplatin) or cisplatin (LC-cisplatin) were selected from PharMetrics’ (IMS LifeLink) claims dataset (2005-2008). Patients were followed for 6 months from initial CT administration for CINV events identified through ICD-9-CM codes. Patients were grouped into those initiated with older, generic 5-HT3 RAs (ondansetron, granisetron, and dolasetron) and those initiated and maintained on palonosetron throughout study follow-up. CINV events and CINV days were analyzed using multivariate regressions controlling for demographic and clinical variables.ResultsEligible patients numbered 3,606 in BC, 4,497 in LC-carboplatin and 1,154 in LC-cisplatin cohorts, with 52%, 40%, and 34% in the palonosetron group, respectively. There was no significant difference between the two 5-HT3 RA groups in age or Charlson Comorbidity Index among the two MEC cohorts (BC and LC-carboplatin). Among the LC-cisplatin cohort, palonosetron users were older with more males than the older 5-HT3 RA group (age: 60.1 vs. 61.3; males, 66.9% vs. 56.9%). Compared to the older 5-HT3 RAs, the palonosetron groups incurred 22%-51% fewer 5-HT3 RA pharmacy claims, had fewer patients with CINV events (3.5% vs. 5.5% in BC, 9.5% vs. 12.8% in LC-carboplatin, 16.4% vs. 21.7% in LC-cisplatin), and had lower risk for CINV events (odds ratios 0.62, 0.71, or 0.71, respectively; p < 0.05). The BC and LC-carboplatin palonosetron groups experienced 50% and 30% fewer CINV days than the generic 5-HT3 RA group (p < 0.05).ConclusionsPatients with breast or lung cancer initiated and maintained on palonosetron were at significantly lower risk for potentially costly CINV versus those on older 5-HT3 RAs. Further studies on impact of step therapy policy are warranted in order to minimize the clinical and economic burden of CINV.

Highlights

Antiemetics including the 5-hydroxytryptamine receptor antagonists (5-HT3 RAs) have been used as prophylaxis against chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately (MEC) or highly emetogenic (HEC) chemotherapy [1,2]
The objectives of the study were to: 1) identify patterns of therapy with 5-HT3 RA-based antiemetic regimens indicative of step therapy approaches in patients newly treated with MEC or HEC, 2) explore the characteristics of patients and health plans associated with 5-HT3 RA step therapy prescribing patterns, and 3) evaluate the impact of a step therapy approach of initiating patients on an older 5-HT3 RA before using palonosetron with regard to differences in the incidence of hospital/emergency department (ED) associated CINV events
The study included patients diagnosed with breast cancer (BC) who received adjuvant chemotherapy with cyclophosphamide within four months after surgery, along with patients diagnosed with lung cancer (LC) who received carboplatin (LC-carboplatin), and patients diagnosed with lung cancer (LC) who received cisplatin-based chemotherapy (LC-cisplatin)

Summary

Introduction

Antiemetics including the 5-hydroxytryptamine receptor antagonists (5-HT3 RAs) have been used as prophylaxis against chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately (MEC) or highly emetogenic (HEC) chemotherapy [1,2]. W tron (Aloxi ) is a newer 5-HT3 RA, approved in the US in 2003 for antiemetic prophylaxis in patients with cancer receiving MEC or HEC. Palonosetron is a potent and highly selective 5-HT3 RA with a strong binding affinity and a longer plasmaelimination half-life relative to the older 5-HT3 RAs [3]. In four phase III trials, two in MEC and two in HEC, palonosetron was reported to have improved efficacy relative to the older 5-HT3 RAs in the prevention of nausea and vomiting associated with initial and repeat courses of MEC or HEC [2,6,7,8]. The available pre-clinical and clinical evidence suggests that the control of CINV in the delayed phase is a true pharmacological effect reflecting the unique properties of palonosetron rather than a carryover effect from better control during the acute phase [9]

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