Hatoum, H.T., Lin, S.J., Buchner, D., & Cox, D. (2012). Comparative clinical effectiveness of various 5-HT₃ RA antiemetic regimens on chemotherapy-induced nausea and vomiting associated with hospital and emergency department visits in real world practice. Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer, 20(5), 941–949.

To compare the risk of chemotherapy-induced nausea and vomiting (CINV) events for various 5-HT₃ receptor antagonists (RAs) in patients who received moderately (MEC) or highly emetogenic chemotherapy (HEC) by evaluating hospital or emergency department (ED) admissions

Patients with breast cancer who received adjuvant chemotherapy with cyclophosphamide within four months after surgery and patients with lung cancer who were initiated on carboplatin or cisplatin-based chemotherapy within the study time frame (January 1, 2005, through June 20, 2008) were identified using the PharMetrics database. CINV events associated with hospital and ED admissions were extracted using claims with ICD-9-CM codes for nausea, vomiting, or dehydration.  

In each cohort, patients were stratified into two groups, one consisting of patients initiated and maintained on palonosetron as the only 5-HT₃ RA antiemetic, the other with patients who were initiated on one of the older 5-HT₃ RAs and maintained on the same agent or alternated throughout the study duration between the older 5-HT₃ RA and palonosetron, either as single agents or in combinations. The use of aprepitant and dexamethasone was used in both cohorts.

The study consisted of 4,868 patients with breast cancer and 7,106 patients with lung cancer (5,414 treated with carboplatin, 1,692 treated with cisplatin).

The median age in all cohorts ranged from 53–65 years.

The breast cancer cohort was 100% female.

The carboplatin-treated lung cancer cohort was 46.5% female and 53.5% male.

The cisplatin-treated lung cancer cohort was 40.3% female and 59.7% male.

The patients in the breast cancer and carboplatin-treated lung cancer cohorts were considered to be treated with moderately emetogenic chemotherapy (MEC). The cisplatin-lung cancer cohort was considered to be treated with highly emetogenic chemotherapy (HEC). The authors did control for differences in age, Charlson comorbidity index (CCI) score, gender (lung cancer cohorts), cyclophosphamide dose per square meter per cycle (breast cancer cohort), and cisplatin and carboplatin treatment days (lung cancer cohorts).

Site and setting type was not indicated. Data was analyzed using pooled patient information from PharMetrics database.

• Patients were in active treatment.
• This study has application to elderly care.

This was a retrospective data analysis.

• Patient comorbidities for the six-month baseline period prior to the study index date were calculated using the CCI.
• The study population was selected using the PharMetrics database.

Based on the results presented by the authors, patients with breast or lung cancer treated with HEC or MEC, when initiated and maintained on palonosetron throughout chemotherapy, experienced significantly reduced risk of hospital- and ED-associated CINV events compared to patients who received other 5-HT₃ RA-based regimens. In all three cohorts, the p value was < 0.0001. The results of the data analysis do show superiority of palensetron in reducing such events, but a number of variables and limitations may impact the results.

Antiemetic regimens containing palonosetron may be more effective in reducing severe, uncontrolled CINV than other 5-HT₃ agents; however, firm conclusions cannot be drawn because of study design limitations and risks of bias.

• No appropriate control group was included.
• The lead author was a paid consultant to Easai, Inc., the marketer of oalonosetron in the USA. Easai, Inc was also the sponsor of the study. The other authors are employees of Easai, Inc. This has the potential to lead to further selection bias of the patient population.
• A large variable that was unaccounted for was the varying doses of chemotherapy. 
  • The average dose of cyclophosphomide used in the breast cancer cohort was on the lower end of dosing. Cyclophosphomide is typically given in a dose of 300-600 mg/m² as adjuvant therapy to patients with breast cancer depending on the selected regimen. The average dose used in patients in this study was 414 mg.
  • Only 19% of patients treated with cisplatin were treated with guideline recommended triplet antiemetic therapy.
• Though an effort was made to control for comorbid conditions in the cohorts, variables such as differences in chemotherapy doses were not a part of the analysis.

The study is helpful because it was an analysis of a large group of patients. It also seeks to provide meaningful conclusions for patients. Although identifying interventions for the reduction of CINV in patients can aid in quality of life and ability to receive treatment in a timely manner, looking at the significance of CINV reduction in preventing serious events such as ED visits or hospitalizations is also important.