Lin, S.J., Hatoum, H.T., Buchner, D., Cox, D., & Balu, S. (2012). Impact of 5-HT3 receptor antagonists on chemotherapy-induced nausea and vomiting: A retrospective cohort study. BMC Health Services Research, 12, 215.

DOI Link

Study Purpose

To study the effect of step-therapy policy requiring an older 5-HT3 receptor antagonist (RA) prior to palonosetron on the risk of chemotherapy-induced nausea and vomiting (CINV) associated with hospital or emergency department (ED) admissions

Intervention Characteristics/Basic Study Process

Patients with a diagnosis of breast or lung cancer and receiving moderately emetogenic chemotherapy (MEC) (cyclophosphamide, carboplatin) or highly emetogenic chemotherapy (HEC) (cisplatin) were selected from the PharmMetrics claims dataset (providing drug name, quantity dispensed, and length of supply) between January 2005 and June 2008. CINV events were followed for six months from initial chemotherapy administration through ICD-9-CM codes. Study duration was six months from the index chemotherapy date, and antiemetics investigated included dolasetron, granisetron, ondansetron, and palonosetron. Patients were divided into two groups: those initiated with palonosetron and maintained on the drug for the duration of the study and those who began therapy with one of the older 5-HT3 RAs and maintained on the initial drug or alternated between any 5-HT3 RAs. The use of dexamethasone was assessed for both groups. CINV events were calculated using paid and filed claims with ICD-9 codes for nausea, vomiting, or dehydration, and those with hospital admissions were selected.

Sample Characteristics

  • This study reported on 9,257 patients.
  • Ages ranged from 53.7–65.03 years.
  • The sample was 33.6% male and 66.4% female.
  • Patients had been diagnosed with breast or lung cancer.
  • Patients were chosen based on having at least six months of records available prior to the study index date; no prior history of vomiting, nausea, or dehydration during the six months preceding the index chemotherapy; and a follow-up period of at least six months after the first date of the first chemotherapy treatment cycle.

Setting

The study was conducted in multiple settings in the United States. Specific sites were not reported.

Phase of Care and Clinical Applications

All patients were in active antitumor treatment.

Study Design

This was a longitudinal, retrospective cohort study.

Measurement Instruments/Methods

  • Severity of patient conditions identified through comorbidities were summarized using an aggregate measure, the Charlson Comorbidity Index (CCI).
  • CINV events associated with hospital/ED admissions were selected.
  • Investigators calculated treatment days with CINV events.

Results

The palonosetron group in all three study cohorts used significantly less antiemetic intervention than that used by those receiving older 5-HT3 RAs. The mean number of 5-HT3 RA claims in the breast cancer cohort was 6.2 days in the palonosetron group versus 7.9 in the older 5-HT3 RA group. Similarly, the mean claims were 7.7 and 10.3 for the two comparison groups in the LC carboplatin cohort and 6.4 and 13.1 in the LC cisplatin cohort (all p < 0.0001). Patients with palonosetron had a statistically reduced risk of hospitalization or ED-associated CINV events compared to older 5HT3 RAs in the three cohort groups (overall response [OR] = 0.62, p = 0.0035). Higher CCI scores were correlated with significantly increased risk of CINV events, while more chemotherapy days were associated with a reduced risk.

Conclusions

Patients with breast or lung cancer receiving MEC who were initiated and maintained on palonosetron were at significantly lower risk for potentially costly CINV versus those on older 5-HT3 RAs. More studies indicating the impact of step-therapy policy are necessary.

Limitations

  • A risk of bias exists because of the sample characteristics.
  • The authors used selective outcomes reporting.
  • Findings may not be generalizable to other populations.
  • CINV events were based on pharmacy claims and not actual CINV experiences.
  • The majority of these patients had health insurance and, thus, could take palonosetron, which is more expensive. People of low economic status may be unable to obtain coverage for this expensive drug.
  • Additional important variables that could affect patients’ CINV experiences are not found in claims data. These include race, alcohol consumption, cancer staging, and history of motion sickness. The claims dataset used in this study was mainly employer-based. Because the sample had one cohort of breast cancer, more than two-thirds of patients were female, and female patients experience more CINV than males.

Nursing Implications

Patients with breast or lung cancer undergoing MEC or HEC who are initiated and maintained on palonosetron experience fewer CINV events compared to patients receiving older 5-HT3 RAs. Nurses should be aware that palonosetron is more expensive than older 5-HT3 RAs, and, thus, patients with low economic status or who are self-insured may not be able to pay for this drug. The reduced antiemetic claims noted here suggest that cost may be equivalent because palonosetron requires fewer doses.