Wenzell, C.M., Berger, M.J., Blazer, M.A., Crawford, B.S., Griffith, N.L., Wesolowski, R., . . . Layman, R.M. (2013). Pilot study on the efficacy of an ondansetron- versus palonosetron-containing antiemetic regimen prior to highly emetogenic chemotherapy. Supportive Care in Cancer, 21, 2845–2851.

To compare the effect of single-day ondansetron use versus palonosetron in combination with aprepitant and dexamethasone

Patients were stratified into cisplatin and noncisplatin chemotherapy groups and then randomized. On day 1 prior to highly emetogenic chemotherapy (HEC), patients in group 1 received palonosetron at 0.25 mg IV. Group 2 received ondansetron at 24 mg orally 30 minutes before chemotherapy. Both groups received oral aprepitant at 125 mg on day 1 (60 minutes prior to chemotherapy) then 80 mg on days 2 and 3, and oral dexamethasone at 12 mg on day 1 then 8 mg on days 2, 3, and 4. Data were recorded on days 1–6 following chemotherapy administration.

• N = 40 (20 in each arm)  
• AVERAGE AGE = 52.9 years (ondansetron), 50.9 years (palonosetron)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Confirming breast cancer; one patient with lymphoma
• OTHER KEY SAMPLE CHARACTERISTICS: Chemotherapy-naïve or treated with low-emetogenic chemotherapy in the past; receiving first cycle of HEC (doxorubicin pr cyclophosphamide); day 1 of multi-day chemotherapy; patients had Eastern Cooperative Group performance statuses of grades 0–2 and were capable of taking oral medications; did not have an event of vomiting or retching within 24 hours before administration of the study medications; did not receive an antiemetic within 24 hours before study medication administration excluding the use of benzodiazepines; did not experienced grade 2 nausea or greater according to the Common Terminology Criteria for Adverse Events within 24 hours before chemotherapy administration; did not receive strong CYP450 3A4 inducers and/or inhibitors known to cause clinically relevant drug interactions within the week prior to study treatment and continuing through day 5; alanine aminotransferase and/or aspartate aminotransferase < 2.5 times upper limit of normal or total bilirubin < 1.5 times upper limit of normal; no known hypersensitivity to ondansetron, palonosetron, aprepitant, or dexamethasone

• SITE: Single site    
• SETTING TYPE: Outpatient    
• LOCATION: The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University

• PHASE OF CARE: Active antitumor treatment

Prospective, open-label, randomized pilot study

• Patients used a diary.
• Patients were instructed to document the day and time of vomiting, retching, nausea, and rescue antiemetics use in real time. They also were instructed to rate their nausea based on the Common Terminology Criteria for Adverse Events (CTCAE) at the end of each day.
• Follow-up phone calls were made by the investigator to assess medication and diary adherence (day 2 or 3 to capture the acute time period and day 4, 5, or 6 to capture the delayed time period).

Thirteen patients (65%) in the palonosetron arm and eight patients (40%) in the ondansetron arm achieved an overall complete response (CR). In the acute setting, 11 patients (55%) in the ondansetron group and 15 (75%) in the palonosetron group achieved a CR. In the delayed setting, nine patients (45%) in the ondansetron group and 13 (65%) in the palonosetron group achieved a CR. In the ondansetron group, 11 patients reported the use of rescue antiemetics, and in the palonosetron group, seven patients reported antiemetic use (in both acute and delayed time periods). Few patients experienced episodes of retching or vomiting. Seven patients in the ondansetron group and eight in the palonosetron group reported acute nausea. Delayed nausea was reported by 11 patients in the ondansetron group and 12 in palonosetron group.

This pilot study demonstrated a consistently higher rates of CR and lower rates of vomiting and retching in the palonosetron group although there was no statistically significant difference.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Findings not generalizable
• Other limitations/explanation: No stratification of age (younger adults tend to develop more severe chemotherpy-induced nausea and vomiting than older adults)

Take caution before interpreting the results of this study because it did not use the most robust research design (i.e., randomization, blinding, placebo-control) to detect the drug's efficacy. This study highlighted the need to conduct a large, adequately powered study.